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| ID | Type | Description | Link |
|---|---|---|---|
| NCI-2011-02670 | Registry Identifier | CTRP (Clinical Trial Reporting Program) | |
| CDR0000701850 | |||
| AAML1031 | |||
| COG-AAML1031 | |||
| S12-02301 | |||
| AAML1031 | Other Identifier | Children's Oncology Group | |
| AAML1031 | Other Identifier | CTEP | |
| U10CA098543 | U.S. NIH Grant/Contract | View source | |
| U10CA180886 | U.S. NIH Grant/Contract | View source |
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This randomized phase III trial studies how well bortezomib and sorafenib tosylate work in treating patients with newly diagnosed acute myeloid leukemia. Bortezomib and sorafenib tosylate may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving bortezomib and sorafenib tosylate together with combination chemotherapy may be an effective treatment for acute myeloid leukemia.
PRIMARY OBJECTIVES:
I. To compare event-free survival (EFS) and overall survival (OS) in patients with de novo acute myeloid leukemia (AML) without high allelic ratio fms-like tyrosine kinase (FLT3)/internal tandem duplications (ITD)+ mutations who are randomized to standard therapy versus bortezomib/standard combination therapy.
II. To determine the feasibility of combining bortezomib with standard chemotherapy in patients with de novo AML.
III. To compare the OS and EFS of high-risk patients treated with intensive Induction II with historical controls from AAML03P1 and AAML0531.
IV. To determine the feasibility of administering sorafenib (sorafenib tosylate) with standard chemotherapy and in a one year maintenance phase in patients with de novo high allelic ratio FLT3/ITD+ AML.
SECONDARY OBJECTIVES:
I. To assess the anti-leukemic activity of sorafenib in patients with de novo high allelic ratio FLT3/ITD+ AML.
II. To compare the percentage of patients converting from positive minimal residual disease (MRD) to negative MRD after Intensive Induction II with historical controls from AAML03P1 and AAML0531.
III. To compare OS, disease-free survival (DFS), cumulative incidence of relapse, and treatment-related mortality from end of Intensification I between patients allocated to best allogenic donor stem cell transplant (SCT) and comparable patients on AAML0531 who did not receive allogenic donor SCT.
IV. To compare OS, DFS, cumulative incidence of relapse, treatment-related mortality, and severe toxicity between patients allocated to matched family donor SCT on AAML1031 and AAML0531.
V. To assess the health-related quality of life (HRQOL) of patients treated with chemotherapy and stem cell transplant (SCT) for AML.
VI. To evaluate bortezomib pharmacokinetics (PK) in patients receiving the combination regimen.
VII. To obtain sorafenib and metabolite steady state pharmacokinetics and pharmacokinetic-pharmacodynamic data in subjects with FLT3/ITD receiving sorafenib.
VIII. To compare the changes in shortening fraction/ejection fraction over time between patients treated with and without dexrazoxane.
IX. To refine the use of minimal-residual disease (MRD) detection with 4-color flow cytometry.
X. To evaluate the prognostic significance of molecular MRD and its contribution to risk identification with multidimensional flow cytometry (MDF)-based MRD in patients with translocations amenable to quantitative real time (RT)-polymerase chain reaction (PCR) (e.g., t[8;21], inv[16], t[9;11], Wilms tumor 1 [WT1] expression).
XI. To determine the leukemic involvement of the hematopoietic early progenitor cell and its role in defining response to therapy.
XII. To define the leukemic stem cell population in patients with AML. XIII. To determine the prevalence and prognostic significance of molecular abnormalities of WT1, runt-related transcription factor (RUNX)1, mixed-lineage leukemia (MLL)-partial tandem duplication (PTD), tet methylcytosine dioxygenase 2 (TET2), Cbl proto-oncogene, E3 ubiquitin protein ligase (c-CBL), v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog (KIT), and other novel AML-associated genes in pediatric AML.
XIV. Correlate the expression of cluster of differentiation (CD)74 antigen as well as proteasome beta 5-subunit (PSMB5) gene expression and mutation with response to bortezomib.
XV. To evaluate the changes in protein expression and unfolded protein response (UPR) in patients with AML.
XVI. To determine the expression level of wild-type FLT3, and correlate with outcome and in vitro sensitivity to FLT3 inhibition.
XVII. To collect biology specimens at diagnosis, treatment time points, and relapse for future biology studies XVIII. To create a pediatric-specific algorithm to predict the occurrence of grade 2-4 acute graft-versus-host disease (GVHD) prior to its clinical manifestations using a combination of pre-transplant clinical variables and serum GVHD biomarker concentrations in the first weeks after SCT.
OUTLINE: This is a dose-escalation study of sorafenib tosylate. Patients are randomized to Arm A or B or offered treatment on 1 of 6 arms. (Arms A and B are closed to new patient enrollment as of 02/04/2016)
Arm A:
INDUCTION I: Patients receive cytarabine intrathecally (IT) on day 1 and ADE chemotherapy comprising cytarabine intravenously (IV) over 1-30 minutes on days 1-10; daunorubicin hydrochloride IV over 1-15 minutes on days 1, 3, and 5; and etoposide IV over 1-2 hours on days 1-5.
INDUCTION II: Patients with low risk (LR) receive cytarabine IT and ADE chemotherapy as in Induction I. Patients with high risk (HR) receive cytarabine IT on day 1 and MA chemotherapy comprising high-dose cytarabine IV over 1-3 hours on days 1-4, and mitoxantrone IV over 15-30 minutes on days 3-6. Patients who achieve complete remission (CR) proceed to Intensification I (beginning on day 37). Patients with refractory disease are off protocol therapy.
INTENSIFICATION I: Patients receive cytarabine IT on day 1 and AE chemotherapy comprising high-dose cytarabine IV over 1-3 hours, and etoposide IV over 1-2 hours on days 1-5. Patients who achieve CR proceed to Intensification II or stem cell transplantation (SCT) beginning on day 34. Patients with refractory disease are off protocol therapy.
INTENSIFICATION II: Patients with LR receive cytarabine IT on day 1 and MA chemotherapy as in Induction II. Patients with HR and no donor for SCT receive high-dose cytarabine IV over 3 hours on days 1, 2, 8, and 9 and asparaginase intramuscularly (IM) on days 2 and 9.
STEM CELL TRANSPLANTATION (SCT) (HR patients with matched family [MFD] or unrelated donor):
CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV over 30 minutes once daily on days -5 to -2 and busulfan IV over 2 hours 4 times daily on days -5 to -2.
TRANSPLANTATION: Patients undergo allogeneic SCT within 36 to 48 hours after the last dose of busulfan.
GVHD PROPHYLAXIS: Patients receive tacrolimus IV continuously or PO beginning on day -2 and continuing until day 98 (matched sibling donor) or day 180 (with taper) (other related/unrelated donors or cord blood) and methotrexate IV on days 1, 3, and 6 (matched sibling/cord blood donors) or days 1, 3, 6, and 11 (other related/unrelated donors). Patients with unrelated donors also receive antithymocyte globulin IV over 6-8 hours on days -3 to -1.
Arm B:
INDUCTION I: Patients receive cytarabine IT and ADE chemotherapy as in Induction I, Arm A. Patients also receive bortezomib IV over 3-5 seconds on days 1, 4, and 8.
INDUCTION II: Patients with LR receive cytarabine IT, ADE chemotherapy, and bortezomib as in Induction I. Patients with HR receive cytarabine IT and MA chemotherapy as in Induction II, Arm A (HR patients) and bortezomib IV on days 1, 4, and 8.
INTENSIFICATION I: Patients receive cytarabine IT and AE chemotherapy in Arm A, Intensification II, and bortezomib IV on days 1, 4, and 8. Patients who achieve CR proceed to Intensification II or stem cell transplantation (SCT) beginning on day 34. Patients with refractory disease are off protocol therapy.
INTENSIFICATION II: Patients with LR receive cytarabine IT on day 1, MA chemotherapy as in Arm A, Induction II (HR patients), and bortezomib IV on days 1, 4, and 8. Patients with HR and no donor for SCT receive high-dose cytarabine IV over 3 hours on days 1, 2, 8, and 9 and asparaginase intramuscularly (IM) on days 2 and 9.
STEM CELL TRANSPLANTATION (SCT) (HR patients with matched family [MFD] or unrelated donor):
CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV over 30 minutes once daily on days -5 to -2 and busulfan IV over 2 hours 4 times daily on days -5 to -2.
TRANSPLANTATION: Patients undergo allogeneic SCT within 36 to 48 hours after the last dose of busulfan.
GVHD PROPHYLAXIS: Patients receive tacrolimus IV continuously or PO beginning on day -2 and continuing until day 98 (matched sibling donor) or day 180 (with taper) (other related/unrelated donors or cord blood) and methotrexate IV on days 1, 3, and 6 (matched sibling/cord blood donors) or days 1, 3, 6, and 11 (other related/unrelated donors). Patients with unrelated donors also receive antithymocyte globulin IV over 6-8 hours on days -3 to -1.
ARM C (COHORT 1):
INDUCTION II: Patients receive cytarabine IT on day 1, cytarabine IV over 1-30 minutes on days 1-8, daunorubicin hydrochloride IV over 1-15 minutes on days 1, 3, and 5, etoposide IV over 1-2 hours on days 1-5, and sorafenib tosylate PO on days 9-36.
INTENSIFICATION I: Patients receive cytarabine IT and AE chemotherapy in Arm A, Intensification II, and sorafenib tosylate PO on daily on days 6-28.
INTENSIFICATION II: Patients receive cytarabine IT on day 1, MA chemotherapy as in Arm A, Induction II (HR patients), and sorafenib tosylate PO on days 7-34.
STEM CELL TRANSPLANTATION (SCT) (HR patients with matched family [MFD] or unrelated donor):
CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV over 30 minutes once daily on days -5 to -2 and busulfan IV over 2 hours 4 times daily on days -5 to -2.
TRANSPLANTATION: Patients undergo allogeneic SCT within 36 to 48 hours after the last dose of busulfan.
GVHD PROPHYLAXIS: Patients receive tacrolimus IV continuously or PO beginning on day -2 and continuing until day 98 (matched sibling donor) or day 180 (with taper) (other related/unrelated donors or cord blood) and methotrexate IV on days 1, 3, and 6 (matched sibling/cord blood donors) or days 1, 3, 6, and 11 (other related/unrelated donors). Patients with unrelated donors also receive antithymocyte globulin IV over 6-8 hours on days -3 to -1.
MAINTENANCE: Patients receive sorafenib tosylate PO starting on day 40-100 after completion of intensification II or SCT for one year.
ARM C (COHORT 2):
INDUCTION I: Patients receive cytarabine IT and ADE chemotherapy as in Arm A, Induction I and sorafenib tosylate PO at the time of known HR FLT3/ITD+ (including in Induction I and concurrently with chemotherapy).
INDUCTION II: Patients receive cytarabine IT on day 1, cytarabine IV over 1-30 minutes on days 1-8, daunorubicin hydrochloride IV over 1-15 minutes on days 1, 3, and 5, etoposide IV over 1-2 hours on days 1-5, and sorafenib tosylate PO on days 9-36.
INTENSIFICATION I: Patients receive cytarabine IT and AE chemotherapy in Arm A, Intensification II, and sorafenib tosylate PO on daily on days 6-28.
INTENSIFICATION II: Patients receive cytarabine IT on day 1, MA chemotherapy as in Arm A, Induction II (HR patients), and sorafenib tosylate PO on days 7-34.
STEM CELL TRANSPLANTATION (SCT) (HR patients with matched family [MFD] or unrelated donor):
CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV over 30 minutes once daily on days -5 to -2 and busulfan IV over 2 hours 4 times daily on days -5 to -2.
TRANSPLANTATION: Patients undergo allogeneic SCT within 36 to 48 hours after the last dose of busulfan.
GVHD PROPHYLAXIS: Patients receive tacrolimus IV continuously or PO beginning on day -2 and continuing until day 98 (matched sibling donor) or day 180 (with taper) (other related/unrelated donors or cord blood) and methotrexate IV on days 1, 3, and 6 (matched sibling/cord blood donors) or days 1, 3, 6, and 11 (other related/unrelated donors). Patients with unrelated donors also receive antithymocyte globulin IV over 6-8 hours on days -3 to -1.
MAINTENANCE: Patients receive sorafenib tosylate PO starting on day 40-100 after completion of intensification II or SCT for one year.
ARM C (COHORT 3):
INDUCTION I: Patients receive cytarabine IT and ADE chemotherapy as in Arm A, Induction I and sorafenib tosylate PO on days 11-28.
INDUCTION II: Patients receive cytarabine IT on day 1, cytarabine IV over 1-30 minutes on days 1-8, daunorubicin hydrochloride IV over 1-15 minutes on days 1, 3, and 5, etoposide IV over 1-2 hours on days 1-5, and sorafenib tosylate PO on days 9-36.
INTENSIFICATION I: Patients receive cytarabine IT and AE chemotherapy in Arm A, Intensification II, and sorafenib tosylate PO on daily on days 6-28.
INTENSIFICATION II: Patients receive cytarabine IT on day 1, MA chemotherapy as in Arm A, Induction II (HR patients), and sorafenib tosylate PO on days 7-34.
STEM CELL TRANSPLANTATION (SCT) (HR patients with matched family [MFD] or unrelated donor):
CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV over 30 minutes once daily on days -5 to -2 and busulfan IV over 2 hours 4 times daily on days -5 to -2.
TRANSPLANTATION: Patients undergo allogeneic SCT within 36 to 48 hours after the last dose of busulfan.
GVHD PROPHYLAXIS: Patients receive tacrolimus IV continuously or PO beginning on day -2 and continuing until day 98 (matched sibling donor) or day 180 (with taper) (other related/unrelated donors or cord blood) and methotrexate IV on days 1, 3, and 6 (matched sibling/cord blood donors) or days 1, 3, 6, and 11 (other related/unrelated donors). Patients with unrelated donors also receive antithymocyte globulin IV over 6-8 hours on days -3 to -1.
MAINTENANCE: Patients receive sorafenib tosylate PO starting on day 40-100 after completion of intensification II or SCT for one year.
ARM D:
INDUCTION I: Patients with unknown FLT3/ITD status prior to study enrollment receive cytarabine IT and ADE chemotherapy as in Arm A, Induction I. If patients are determined to be HR FLT3/ITD+ no later than the end of Induction I they will be eligible to participate in Arm C.
After completion of study therapy, patients are followed up monthly for 6 months, every 2 months for 6 months, every 4 months for 1 year, every 6 months for 1 year, and then yearly thereafter.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Arm A | Experimental | See Detailed Description |
|
| Arm B | Experimental | See Detailed Description |
|
| Arm C (Cohort 1) | Experimental | See Detailed Description |
|
| Arm C (Cohort 2) | Experimental | See Detailed Description. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Asparaginase | Drug | Given IM |
|
| Measure | Description | Time Frame |
|---|---|---|
| Event-free Survival (EFS) for Patients Without High Allelic Ratio FLT3/ITD+ Mutations | The Kaplan-Meier method will be used to estimate 3-year EFS, defined as the time from study entry until induction failure, relapse, secondary malignancy, or death. | Up to 3 years |
| EFS for Patients on Arm C, Cohort 1 | The Kaplan-Meier method will be used to estimate 3-year EFS, defined as the time from study entry until induction failure, relapse, secondary malignancy, or death. | Up to 3 years |
| EFS for Patients on Arm C, Cohort 2 | The Kaplan-Meier method will be used to estimate 3-year EFS, defined as the time from study entry until induction failure, relapse, secondary malignancy, or death. | Up to 3 years |
| EFS for Patients on Arm C, Cohort 3 | The Kaplan-Meier method will be used to estimate 3-year EFS, defined as the time from study entry until induction failure, relapse, secondary malignancy, or death. | Up to 3 years |
| Measure | Description | Time Frame |
|---|---|---|
| Overall Survival (OS) for Patients Without High Allelic Ratio FLT3/ITD+ Mutations | The Kaplan-Meier method will be used to estimate 3-year OS, defined as the time from study entry until death. | Up to 3 years |
| OS for Patients on Arm C, Cohort 1 |
| Measure | Description | Time Frame |
|---|---|---|
| Course Duration | Descriptive statistics will be used to summarize length of hospitalization time. | Up to 6 months |
| Incidence of Treatment-related Mortality | Cumulative incidence estimates that account for competing events will be used to estimate treatment-related mortality. |
Inclusion Criteria:
Patients must be newly diagnosed with de novo acute myelogenous leukemia
Patients with previously untreated primary AML who meet the customary criteria for AML with >= 20% bone marrow blasts as set out in the 2008 World Health Organization (WHO) Myeloid Neoplasm Classification are eligible
Patients with < 20% bone marrow blasts are eligible if they have:
Patients with any performance status are eligible for enrollment
Prior therapy with hydroxyurea, all-trans retinoic acid (ATRA), corticosteroids (any route), and IT cytarabine given at diagnosis is allowed; hydroxyurea and ATRA must be discontinued prior to initiation of protocol therapy; patients who have previously received any other chemotherapy, radiation therapy or any other antileukemic therapy are not eligible for this protocol
Exclusion Criteria:
Patients with any of the following constitutional conditions are not eligible:
Patients with any of the following oncologic diagnoses are not eligible:
Pregnancy and breast feeding
Female patients who are pregnant are ineligible
Lactating females are not eligible unless they have agreed not to breastfeed their infants
Female patients of childbearing potential are not eligible unless a negative pregnancy test result has been obtained
Sexually active patients of reproductive potential are not eligible unless they have agreed to use an effective contraceptive method for the duration of their study participation
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| Name | Affiliation | Role |
|---|---|---|
| Richard Aplenc | Children's Oncology Group | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Children's Hospital of Alabama | Birmingham | Alabama | 35233 | United States | ||
| University of Alabama at Birmingham Cancer Center |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 42085603 | Derived | Scheidegger N, Schneider C, Alexe G, Wang YC, Alonzo TA, Basanthakumar A, Bourgeois WA, Dudkiewicz-Garbicz J, Khalid D, Merickel LA, Perry JA, Ries RE, Salhotra S, Taillon A, Gamis A, Aplenc R, Harris MH, Wunderlich M, Armstrong SA, Pollard JA, Meshinchi S, Pikman Y, Stegmaier K. Combining menin and MEK inhibition to target poor prognosis KMT2A-rearranged RAS pathway-mutant acute myeloid leukemia. Blood Adv. 2026 Jul 14;10(13):4757-4771. doi: 10.1182/bloodadvances.2025016208. | |
| 40294366 |
| Label | URL |
|---|---|
| Data Available: Select individual patient-level data from this trial can be requested from the NCTN/NCORP Data Archive. | View source |
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Results in the Participant Flow table summarize final (or analysis) arm assignment. Therefore, results for patients on Arms A, B, and D do not include any patient who transferred to Arm C.
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| ID | Title | Description |
|---|---|---|
| FG000 | Arm A | INDUCTION (IND) 1Pts receive intrathecal (IT) cytarabine on day 1 and ADE with IV cytarabine over 1-30 minutes on days 1-10; daunorubicin hydrochloride IV over 1-15 minutes days1, 3, 5; etoposide IV 1-2 hours days 1-5. IND IILow risk (LR) pts receive cytarabine IT and ADE chemotherapy as in INDI. High risk (HR) cytarabine IT day 1, MA chemo comprising high-dose cytarabine IV over 1-3 hours days1-4, mitoxantrone IV over 15-30 minutes days 3-6. INTENSIFICATION (INT) I: cytarabine IT day 1, AE chemo with high-dose cytarabine IV over 1-3 hours, etoposide IV over 1-2 hours days 1-5. INT II: LR-cytarabine IT day 1; Induction II MA chemo. HR and no SCT donor - high-dose cytarabine IV over 3 hours days1, 2, 8, 9; asparaginase intramuscularly (IM) days 2,9. SCT: pts receive fludarabine phosphate IV over 30 minutes once daily days -5 to -2, busulfan IV over 2 hours 4 times daily days -5 to -2. Allogeneic SCT within 36 to 48 hours after last busulfan dose. Pts receive GVHD prophylaxis. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Apr 24, 2017 |
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| Arm C (Cohort 3) | Experimental | See Detailed Description. Different dose. |
|
| Arm D | Experimental | See Detailed Description. May reassigned to Arm C. |
|
| Bortezomib | Drug | Given IV |
|
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| Cytarabine | Drug | Given IT or IV |
|
|
| Daunorubicin Hydrochloride | Drug | Given IV |
|
|
| Etoposide | Drug | Given IV |
|
|
| Laboratory Biomarker Analysis | Other | Correlative studies |
|
| Mitoxantrone Hydrochloride | Drug | Given IV |
|
|
| Pharmacological Study | Other | Correlative studies |
|
| Quality-of-Life Assessment | Other | Ancillary studies |
|
|
| Questionnaire Administration | Other | Ancillary studies |
|
| Sorafenib Tosylate | Drug | Given PO |
|
|
The Kaplan-Meier method will be used to estimate 3-year OS, defined as the time from study entry until death.
| Up to 3 years |
| OS for Patients on Arm C, Cohort 2 | The Kaplan-Meier method will be used to estimate 3-year OS, defined as the time from study entry until death. | Up to 3 years |
| OS for Patients on Arm C, Cohort 3 | The Kaplan-Meier method will be used to estimate 3-year OS, defined as the time from study entry until death. | Up to 3 years |
| Relapse Rate for Patients Without High Allelic Ratio FLT3/ITD+ Mutations | Cumulative incidence estimates 3 year relapse rate defined as time from study entry to induction failure or relapse where deaths or secondary malignancies are competing events. | Up to 3 years |
| Proportion of Patients Experiencing Grade 3 or Higher Non-hematologic Toxicities and Infections While on Protocol Therapy | The proportion of patients experiencing at least one grade 3 or higher non-hematologic toxicity and infection while on protocol therapy will be estimated along with the corresponding 95% confidence interval determined using a binomial exact method. Toxicity will be assessed by Common Terminology Criteria for Adverse Events version 4.0 (CTCAE v4.0). | Up to 2 years |
| Proportion of High Risk Children Without HR FLT3/ITD+ Converting From Positive MRD at End of Induction I to Negative MRD at the End of Induction II | The proportion of high risk children without HR FLT3/ITD+ converting from positive MRD at end of Induction I to negative MRD at the end of Induction II will be estimated as well as the corresponding 95% confidence interval determined using a binomial exact method. | Up to 8 weeks |
| Total Scale Score From Parent-reported Pediatric Quality of Life Inventory Module | Results represent the total scale scores from the parent report of the PedsQLâ„¢ 4.0 Generic Core Scales for timepoint 1 (up to 14 days from start of therapy). Items are reverse-scored and linearly transformed to a 0-100 scale as follows: 0=100, 1=75, 2=50, 3=25, 4=0. Therefore, a higher number is a better outcome. The total score is the sum of all the items divided by the number of items answered on all the scales. "Scores on a scale" is used for a unit of measure. | Up to 14 days |
| Total Scale Score From Parent-reported Cancer Module | Results represent the total scale scores from the parent report of the PedsQLâ„¢ 3.0 Cancer Module for timepoint 1 (up to 14 days from start of therapy). Items are reverse-scored and linearly transformed to a 0-100 scale as follows: 0=100, 1=75, 2=50, 3=25, 4=0. Therefore, a higher number is a better outcome. The total score is the sum of all the items divided by the number of items answered on all the scales. "Scores on a scale" is used for a unit of measure. | Up to 14 days |
| Total Scale Score From Parent-reported Multidimensional Fatigue Scale Module | Results represent the total scale scores from the parent report of the PedsQLâ„¢ Multidimensional Fatigue Scale for timepoint 1 (up to 14 days from start of therapy). Items are reverse-scored and linearly transformed to a 0-100 scale as follows: 0=100, 1=75, 2=50, 3=25, 4=0. Therefore, a higher number is a better outcome. The total score is the sum of all the items divided by the number of items answered on all the scales. "Scores on a scale" is used for a unit of measure. | Up to 14 days |
| Bortezomib Clearance | Median and range of bortezomib clearance during Induction II. | Day 8 of Induction II |
| Sorafenib Steady State Concentration | Median and range of sorafenib steady state concentration for Induction I. | Up to 30 days |
| Change in Shortening Fraction | Mean percentage change in shortening fraction from baseline to the end of Induction I will be determined for eligible patients enrolled on Arms A, B and C. | Up to 4 weeks |
| Change in Ejection Fraction | The mean percentage change in ejection fraction from baseline to the end of Induction I will be determined for eligible patients enrolled on Arms A, B and C. | Up to 4 weeks |
| Serum Concentrations of GVHD Biomarker | The mean serum concentration of the day 28 GVHD biomarker will be estimated as well as the corresponding 95% confidence interval. | Up to day 28 after SCT |
| Up to 2 years |
| Length of Hospitalization | Descriptive statistics will be used to summarize length of hospitalization time. | Up to 6 months |
| Remission Rate After 1 Course of Therapy | The proportion of patients achieving remission after 1 course of therapy will be estimated along with a corresponding 95% confidence interval. | 4 weeks |
| Remission Rate After 2 Courses of Therapy | The proportion of patients achieving remission after 2 courses of therapy will be estimated along with a corresponding 95% confidence interval. | 8 weeks |
| Time to Blood Count Recovery | Cumulative incidence estimates that account for competing events will be used to estimate time to count recovery. | Up to 6 months |
| Birmingham |
| Alabama |
| 35233 |
| United States |
| USA Health Strada Patient Care Center | Mobile | Alabama | 36604 | United States |
| Banner Children's at Desert | Mesa | Arizona | 85202 | United States |
| Phoenix Childrens Hospital | Phoenix | Arizona | 85016 | United States |
| Banner University Medical Center - Tucson | Tucson | Arizona | 85719 | United States |
| Arkansas Children's Hospital | Little Rock | Arkansas | 72202-3591 | United States |
| University of Arkansas for Medical Sciences | Little Rock | Arkansas | 72205 | United States |
| Kaiser Permanente Downey Medical Center | Downey | California | 90242 | United States |
| City of Hope Comprehensive Cancer Center | Duarte | California | 91010 | United States |
| Loma Linda University Medical Center | Loma Linda | California | 92354 | United States |
| Miller Children's and Women's Hospital Long Beach | Long Beach | California | 90806 | United States |
| Children's Hospital Los Angeles | Los Angeles | California | 90027 | United States |
| Cedars-Sinai Medical Center | Los Angeles | California | 90048 | United States |
| Valley Children's Hospital | Madera | California | 93636 | United States |
| UCSF Benioff Children's Hospital Oakland | Oakland | California | 94609 | United States |
| Kaiser Permanente-Oakland | Oakland | California | 94611 | United States |
| Children's Hospital of Orange County | Orange | California | 92868 | United States |
| Lucile Packard Children's Hospital Stanford University | Palo Alto | California | 94304 | United States |
| Sutter Medical Center Sacramento | Sacramento | California | 95816 | United States |
| University of California Davis Comprehensive Cancer Center | Sacramento | California | 95817 | United States |
| Rady Children's Hospital - San Diego | San Diego | California | 92123 | United States |
| UCSF Medical Center-Parnassus | San Francisco | California | 94143 | United States |
| UCSF Medical Center-Mission Bay | San Francisco | California | 94158 | United States |
| Santa Barbara Cottage Hospital | Santa Barbara | California | 93102 | United States |
| Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center | Torrance | California | 90502 | United States |
| Children's Hospital Colorado | Aurora | Colorado | 80045 | United States |
| Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center | Denver | Colorado | 80218 | United States |
| Connecticut Children's Medical Center | Hartford | Connecticut | 06106 | United States |
| Yale University | New Haven | Connecticut | 06520 | United States |
| Alfred I duPont Hospital for Children | Wilmington | Delaware | 19803 | United States |
| MedStar Georgetown University Hospital | Washington D.C. | District of Columbia | 20007 | United States |
| Children's National Medical Center | Washington D.C. | District of Columbia | 20010 | United States |
| Broward Health Medical Center | Fort Lauderdale | Florida | 33316 | United States |
| Lee Memorial Health System | Fort Myers | Florida | 33901 | United States |
| Golisano Children's Hospital of Southwest Florida | Fort Myers | Florida | 33908 | United States |
| UF Health Cancer Institute - Gainesville | Gainesville | Florida | 32610 | United States |
| Memorial Regional Hospital/Joe DiMaggio Children's Hospital | Hollywood | Florida | 33021 | United States |
| Nemours Children's Clinic-Jacksonville | Jacksonville | Florida | 32207 | United States |
| University of Miami Miller School of Medicine-Sylvester Cancer Center | Miami | Florida | 33136 | United States |
| Nicklaus Children's Hospital | Miami | Florida | 33155 | United States |
| Miami Cancer Institute | Miami | Florida | 33176 | United States |
| AdventHealth Orlando | Orlando | Florida | 32803 | United States |
| Arnold Palmer Hospital for Children | Orlando | Florida | 32806 | United States |
| Nemours Children's Clinic - Orlando | Orlando | Florida | 32806 | United States |
| Orlando Health Cancer Institute | Orlando | Florida | 32806 | United States |
| Nemours Children's Hospital | Orlando | Florida | 32827 | United States |
| Nemours Children's Clinic - Pensacola | Pensacola | Florida | 32504 | United States |
| Johns Hopkins All Children's Hospital | St. Petersburg | Florida | 33701 | United States |
| Tampa General Hospital | Tampa | Florida | 33606 | United States |
| Saint Joseph's Hospital/Children's Hospital-Tampa | Tampa | Florida | 33607 | United States |
| Saint Mary's Medical Center | West Palm Beach | Florida | 33407 | United States |
| Children's Healthcare of Atlanta - Arthur M Blank Hospital | Atlanta | Georgia | 30329 | United States |
| Augusta University Medical Center | Augusta | Georgia | 30912 | United States |
| Memorial Health University Medical Center | Savannah | Georgia | 31404 | United States |
| University of Hawaii Cancer Center | Honolulu | Hawaii | 96813 | United States |
| Kapiolani Medical Center for Women and Children | Honolulu | Hawaii | 96826 | United States |
| Saint Luke's Cancer Institute - Boise | Boise | Idaho | 83712 | United States |
| Lurie Children's Hospital-Chicago | Chicago | Illinois | 60611 | United States |
| University of Illinois | Chicago | Illinois | 60612 | United States |
| University of Chicago Comprehensive Cancer Center | Chicago | Illinois | 60637 | United States |
| Loyola University Medical Center | Maywood | Illinois | 60153 | United States |
| Advocate Children's Hospital-Oak Lawn | Oak Lawn | Illinois | 60453 | United States |
| Advocate Children's Hospital-Park Ridge | Park Ridge | Illinois | 60068 | United States |
| Advocate Lutheran General Hospital | Park Ridge | Illinois | 60068 | United States |
| Southern Illinois University School of Medicine | Springfield | Illinois | 62702 | United States |
| Riley Hospital for Children | Indianapolis | Indiana | 46202 | United States |
| Ascension Saint Vincent Indianapolis Hospital | Indianapolis | Indiana | 46260 | United States |
| Blank Children's Hospital | Des Moines | Iowa | 50309 | United States |
| University of Iowa/Holden Comprehensive Cancer Center | Iowa City | Iowa | 52242 | United States |
| University of Kentucky/Markey Cancer Center | Lexington | Kentucky | 40536 | United States |
| Norton Children's Hospital | Louisville | Kentucky | 40202 | United States |
| Tulane University School of Medicine | New Orleans | Louisiana | 70112 | United States |
| Children's Hospital New Orleans | New Orleans | Louisiana | 70118 | United States |
| Ochsner Medical Center Jefferson | New Orleans | Louisiana | 70121 | United States |
| Eastern Maine Medical Center | Bangor | Maine | 04401 | United States |
| Maine Children's Cancer Program | Scarborough | Maine | 04074 | United States |
| University of Maryland/Greenebaum Cancer Center | Baltimore | Maryland | 21201 | United States |
| Sinai Hospital of Baltimore | Baltimore | Maryland | 21215 | United States |
| Johns Hopkins University/Sidney Kimmel Cancer Center | Baltimore | Maryland | 21287 | United States |
| Walter Reed National Military Medical Center | Bethesda | Maryland | 20889-5600 | United States |
| Tufts Children's Hospital | Boston | Massachusetts | 02111 | United States |
| Massachusetts General Hospital Cancer Center | Boston | Massachusetts | 02114 | United States |
| Dana-Farber Cancer Institute | Boston | Massachusetts | 02215 | United States |
| Baystate Medical Center | Springfield | Massachusetts | 01199 | United States |
| UMass Memorial Medical Center - University Campus | Worcester | Massachusetts | 01655 | United States |
| C S Mott Children's Hospital | Ann Arbor | Michigan | 48109 | United States |
| Wayne State University/Karmanos Cancer Institute | Detroit | Michigan | 48201 | United States |
| Henry Ford Health Saint John Hospital | Detroit | Michigan | 48236 | United States |
| Michigan State University | East Lansing | Michigan | 48823 | United States |
| Hurley Medical Center | Flint | Michigan | 48503 | United States |
| Corewell Health Grand Rapids Hospitals - Helen DeVos Children's Hospital | Grand Rapids | Michigan | 49503 | United States |
| Bronson Methodist Hospital | Kalamazoo | Michigan | 49007 | United States |
| Corewell Health Children's | Royal Oak | Michigan | 48073 | United States |
| Children's Hospitals and Clinics of Minnesota - Minneapolis | Minneapolis | Minnesota | 55404 | United States |
| University of Minnesota/Masonic Cancer Center | Minneapolis | Minnesota | 55455 | United States |
| Mayo Clinic in Rochester | Rochester | Minnesota | 55905 | United States |
| University of Mississippi Medical Center | Jackson | Mississippi | 39216 | United States |
| University of Missouri Children's Hospital | Columbia | Missouri | 65212 | United States |
| Children's Mercy Hospitals and Clinics | Kansas City | Missouri | 64108 | United States |
| Washington University School of Medicine | St Louis | Missouri | 63110 | United States |
| Mercy Hospital Saint Louis | St Louis | Missouri | 63141 | United States |
| Children's Hospital and Medical Center of Omaha | Omaha | Nebraska | 68114 | United States |
| University of Nebraska Medical Center | Omaha | Nebraska | 68198 | United States |
| University Medical Center of Southern Nevada | Las Vegas | Nevada | 89102 | United States |
| Sunrise Hospital and Medical Center | Las Vegas | Nevada | 89109 | United States |
| Nevada Cancer Research Foundation NCORP | Las Vegas | Nevada | 89120 | United States |
| Alliance for Childhood Diseases/Cure 4 the Kids Foundation | Las Vegas | Nevada | 89135 | United States |
| Summerlin Hospital Medical Center | Las Vegas | Nevada | 89144 | United States |
| Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center | Lebanon | New Hampshire | 03756 | United States |
| Hackensack University Medical Center | Hackensack | New Jersey | 07601 | United States |
| Saint Barnabas Medical Center | Livingston | New Jersey | 07039 | United States |
| Morristown Medical Center | Morristown | New Jersey | 07960 | United States |
| Saint Peter's University Hospital | New Brunswick | New Jersey | 08901 | United States |
| Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital | New Brunswick | New Jersey | 08903 | United States |
| Newark Beth Israel Medical Center | Newark | New Jersey | 07112 | United States |
| Saint Joseph's Regional Medical Center | Paterson | New Jersey | 07503 | United States |
| Overlook Hospital | Summit | New Jersey | 07902 | United States |
| University of New Mexico Cancer Center | Albuquerque | New Mexico | 87106 | United States |
| Albany Medical Center | Albany | New York | 12208 | United States |
| Roswell Park Cancer Institute | Buffalo | New York | 14263 | United States |
| NYU Langone Hospital - Long Island | Mineola | New York | 11501 | United States |
| The Steven and Alexandra Cohen Children's Medical Center of New York | New Hyde Park | New York | 11040 | United States |
| Laura and Isaac Perlmutter Cancer Center at NYU Langone | New York | New York | 10016 | United States |
| Mount Sinai Hospital | New York | New York | 10029 | United States |
| NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center | New York | New York | 10032 | United States |
| Memorial Sloan Kettering Cancer Center | New York | New York | 10065 | United States |
| NYP/Weill Cornell Medical Center | New York | New York | 10065 | United States |
| University of Rochester | Rochester | New York | 14642 | United States |
| Stony Brook University Medical Center | Stony Brook | New York | 11794 | United States |
| State University of New York Upstate Medical University | Syracuse | New York | 13210 | United States |
| Montefiore Medical Center - Moses Campus | The Bronx | New York | 10467 | United States |
| New York Medical College | Valhalla | New York | 10595 | United States |
| Mission Hospital | Asheville | North Carolina | 28801 | United States |
| UNC Lineberger Comprehensive Cancer Center | Chapel Hill | North Carolina | 27599 | United States |
| Carolinas Medical Center/Levine Cancer Institute | Charlotte | North Carolina | 28203 | United States |
| Novant Health Presbyterian Medical Center | Charlotte | North Carolina | 28204 | United States |
| Duke University Medical Center | Durham | North Carolina | 27710 | United States |
| Wake Forest University Health Sciences | Winston-Salem | North Carolina | 27157 | United States |
| Sanford Broadway Medical Center | Fargo | North Dakota | 58122 | United States |
| Children's Hospital Medical Center of Akron | Akron | Ohio | 44308 | United States |
| Cincinnati Children's Hospital Medical Center | Cincinnati | Ohio | 45229 | United States |
| Rainbow Babies and Childrens Hospital | Cleveland | Ohio | 44106 | United States |
| Cleveland Clinic Foundation | Cleveland | Ohio | 44195 | United States |
| Nationwide Children's Hospital | Columbus | Ohio | 43205 | United States |
| Dayton Children's Hospital | Dayton | Ohio | 45404 | United States |
| ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital | Toledo | Ohio | 43606 | United States |
| Mercy Children's Hospital | Toledo | Ohio | 43608 | United States |
| University of Oklahoma Health Sciences Center | Oklahoma City | Oklahoma | 73104 | United States |
| Legacy Emanuel Children's Hospital | Portland | Oregon | 97227 | United States |
| Legacy Emanuel Hospital and Health Center | Portland | Oregon | 97227 | United States |
| Oregon Health and Science University | Portland | Oregon | 97239 | United States |
| Lehigh Valley Hospital - Muhlenberg | Bethlehem | Pennsylvania | 18017 | United States |
| Geisinger Medical Center | Danville | Pennsylvania | 17822 | United States |
| Penn State Children's Hospital | Hershey | Pennsylvania | 17033 | United States |
| Children's Hospital of Philadelphia | Philadelphia | Pennsylvania | 19104 | United States |
| Saint Christopher's Hospital for Children | Philadelphia | Pennsylvania | 19134 | United States |
| Children's Hospital of Pittsburgh of UPMC | Pittsburgh | Pennsylvania | 15224 | United States |
| Rhode Island Hospital | Providence | Rhode Island | 02903 | United States |
| Medical University of South Carolina | Charleston | South Carolina | 29425 | United States |
| Prisma Health Richland Hospital | Columbia | South Carolina | 29203 | United States |
| BI-LO Charities Children's Cancer Center | Greenville | South Carolina | 29605 | United States |
| Sanford USD Medical Center - Sioux Falls | Sioux Falls | South Dakota | 57117-5134 | United States |
| T C Thompson Children's Hospital | Chattanooga | Tennessee | 37403 | United States |
| East Tennessee Childrens Hospital | Knoxville | Tennessee | 37916 | United States |
| Vanderbilt University/Ingram Cancer Center | Nashville | Tennessee | 37232 | United States |
| Dell Children's Medical Center of Central Texas | Austin | Texas | 78723 | United States |
| Driscoll Children's Hospital | Corpus Christi | Texas | 78411 | United States |
| Medical City Dallas Hospital | Dallas | Texas | 75230 | United States |
| UT Southwestern/Simmons Cancer Center-Dallas | Dallas | Texas | 75390 | United States |
| El Paso Children's Hospital | El Paso | Texas | 79905 | United States |
| Brooke Army Medical Center | Fort Sam Houston | Texas | 78234 | United States |
| Cook Children's Medical Center | Fort Worth | Texas | 76104 | United States |
| Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center | Houston | Texas | 77030 | United States |
| Covenant Children's Hospital | Lubbock | Texas | 79410 | United States |
| Children's Hospital of San Antonio | San Antonio | Texas | 78207 | United States |
| Methodist Children's Hospital of South Texas | San Antonio | Texas | 78229 | United States |
| University of Texas Health Science Center at San Antonio | San Antonio | Texas | 78229 | United States |
| Scott and White Memorial Hospital | Temple | Texas | 76508 | United States |
| Primary Children's Hospital | Salt Lake City | Utah | 84113 | United States |
| University of Vermont and State Agricultural College | Burlington | Vermont | 05405 | United States |
| Inova Fairfax Hospital | Falls Church | Virginia | 22042 | United States |
| Children's Hospital of The King's Daughters | Norfolk | Virginia | 23507 | United States |
| VCU Massey Comprehensive Cancer Center | Richmond | Virginia | 23298 | United States |
| Carilion Children's | Roanoke | Virginia | 24014 | United States |
| Seattle Children's Hospital | Seattle | Washington | 98105 | United States |
| Providence Sacred Heart Medical Center and Children's Hospital | Spokane | Washington | 99204 | United States |
| Mary Bridge Children's Hospital and Health Center | Tacoma | Washington | 98405 | United States |
| Madigan Army Medical Center | Tacoma | Washington | 98431 | United States |
| West Virginia University Charleston Division | Charleston | West Virginia | 25304 | United States |
| West Virginia University Healthcare | Morgantown | West Virginia | 26506 | United States |
| Saint Vincent Hospital Cancer Center Green Bay | Green Bay | Wisconsin | 54301 | United States |
| University of Wisconsin Carbone Cancer Center - University Hospital | Madison | Wisconsin | 53792 | United States |
| Marshfield Medical Center-Marshfield | Marshfield | Wisconsin | 54449 | United States |
| Children's Hospital of Wisconsin | Milwaukee | Wisconsin | 53226 | United States |
| John Hunter Children's Hospital | Hunter Regional Mail Centre | New South Wales | 2310 | Australia |
| Sydney Children's Hospital | Randwick | New South Wales | 2031 | Australia |
| The Children's Hospital at Westmead | Westmead | New South Wales | 2145 | Australia |
| Royal Brisbane and Women's Hospital | Herston | Queensland | 4029 | Australia |
| Royal Children's Hospital-Brisbane | Herston | Queensland | 4029 | Australia |
| Queensland Children's Hospital | South Brisbane | Queensland | 4101 | Australia |
| Royal Children's Hospital | Parkville | Victoria | 3052 | Australia |
| Princess Margaret Hospital for Children | Perth | Western Australia | 6008 | Australia |
| Alberta Children's Hospital | Calgary | Alberta | T3B 6A8 | Canada |
| University of Alberta Hospital | Edmonton | Alberta | T6G 2B7 | Canada |
| British Columbia Children's Hospital | Vancouver | British Columbia | V6H 3V4 | Canada |
| CancerCare Manitoba | Winnipeg | Manitoba | R3E 0V9 | Canada |
| Janeway Child Health Centre | St. John's | Newfoundland and Labrador | A1B 3V6 | Canada |
| IWK Health Centre | Halifax | Nova Scotia | B3K 6R8 | Canada |
| McMaster Children's Hospital at Hamilton Health Sciences | Hamilton | Ontario | L8N 3Z5 | Canada |
| Kingston Health Sciences Centre | Kingston | Ontario | K7L 2V7 | Canada |
| Children's Hospital | London | Ontario | N6A 5W9 | Canada |
| Children's Hospital of Eastern Ontario | Ottawa | Ontario | K1H 8L1 | Canada |
| Hospital for Sick Children | Toronto | Ontario | M5G 1X8 | Canada |
| The Montreal Children's Hospital of the MUHC | Montreal | Quebec | H3H 1P3 | Canada |
| Centre Hospitalier Universitaire Sainte-Justine | Montreal | Quebec | H3T 1C5 | Canada |
| CHU de Quebec-Centre Hospitalier de l'Universite Laval (CHUL) | Québec | G1V 4G2 | Canada |
| Starship Children's Hospital | Grafton | Auckland | 1145 | New Zealand |
| Christchurch Hospital | Christchurch | 8011 | New Zealand |
| San Jorge Children's Hospital | San Juan | 00912 | Puerto Rico |
| Huang BJ, Meyer LK, Alonzo TA, Wang YC, Lamble AJ, Ries RE, Wang W, Hirsch B, Raca G, Ma X, Gamis AS, Aplenc R, Kolb EA, Cooper TM, Tarlock K, Loken MR, Meshinchi S, Chewning JH, Woods WG, Horan JT. Hematopoietic Stem Cell Transplantation Outcomes for High-Risk AML: A Report From the Children's Oncology Group. J Clin Oncol. 2025 Jun 10;43(17):1961-1971. doi: 10.1200/JCO-24-01841. Epub 2025 Apr 28. |
| 38295280 | Derived | Tarlock K, Gerbing RB, Ries RE, Smith JL, Leonti A, Huang BJ, Kirkey D, Robinson L, Peplinski JH, Lange B, Cooper TM, Gamis AS, Kolb EA, Aplenc R, Pollard JA, Alonzo TA, Meshinchi S. Prognostic impact of cooccurring mutations in FLT3-ITD pediatric acute myeloid leukemia. Blood Adv. 2024 May 14;8(9):2094-2103. doi: 10.1182/bloodadvances.2023011980. |
| 37267439 | Derived | Zarnegar-Lumley S, Alonzo TA, Gerbing RB, Othus M, Sun Z, Ries RE, Wang J, Leonti A, Kutny MA, Ostronoff F, Radich JP, Appelbaum FR, Pogosova-Agadjanyan EL, O'Dwyer K, Tallman MS, Litzow M, Atallah E, Cooper TM, Aplenc RA, Abdel-Wahab O, Gamis AS, Luger S, Erba H, Levine R, Kolb EA, Stirewalt DL, Meshinchi S, Tarlock K. Characteristics and prognostic impact of IDH mutations in AML: a COG, SWOG, and ECOG analysis. Blood Adv. 2023 Oct 10;7(19):5941-5953. doi: 10.1182/bloodadvances.2022008282. |
| 36815378 | Derived | Bertrums EJM, Smith JL, Harmon L, Ries RE, Wang YJ, Alonzo TA, Menssen AJ, Chisholm KM, Leonti AR, Tarlock K, Ostronoff F, Pogosova-Agadjanyan EL, Kaspers GJL, Hasle H, Dworzak M, Walter C, Muhlegger N, Morerio C, Pardo L, Hirsch B, Raimondi S, Cooper TM, Aplenc R, Gamis AS, Kolb EA, Farrar JE, Stirewalt D, Ma X, Shaw TI, Furlan SN, Brodersen LE, Loken MR, Van den Heuvel-Eibrink MM, Zwaan CM, Triche TJ, Goemans BF, Meshinchi S. Comprehensive molecular and clinical characterization of NUP98 fusions in pediatric acute myeloid leukemia. Haematologica. 2023 Aug 1;108(8):2044-2058. doi: 10.3324/haematol.2022.281653. |
| 35349331 | Derived | Pollard JA, Alonzo TA, Gerbing R, Brown P, Fox E, Choi J, Fisher B, Hirsch B, Kahwash S, Getz K, Levine J, Brodersen LE, Loken MR, Raimondi S, Tarlock K, Wood A, Sung L, Kolb EA, Gamis A, Meshinchi S, Aplenc R. Sorafenib in Combination With Standard Chemotherapy for Children With High Allelic Ratio FLT3/ITD+ Acute Myeloid Leukemia: A Report From the Children's Oncology Group Protocol AAML1031. J Clin Oncol. 2022 Jun 20;40(18):2023-2035. doi: 10.1200/JCO.21.01612. Epub 2022 Mar 29. |
| 34855461 | Derived | Lamble AJ, Eidenschink Brodersen L, Alonzo TA, Wang J, Pardo L, Sung L, Cooper TM, Kolb EA, Aplenc R, Tasian SK, Loken MR, Meshinchi S. CD123 Expression Is Associated With High-Risk Disease Characteristics in Childhood Acute Myeloid Leukemia: A Report From the Children's Oncology Group. J Clin Oncol. 2022 Jan 20;40(3):252-261. doi: 10.1200/JCO.21.01595. Epub 2021 Dec 2. |
| 34596937 | Derived | Elgarten CW, Wood AC, Li Y, Alonzo TA, Brodersen LE, Gerbing RB, Getz KD, Huang YV, Loken M, Meshinchi S, Pollard JA, Sung L, Woods WG, Kolb EA, Gamis AS, Aplenc R. Outcomes of intensification of induction chemotherapy for children with high-risk acute myeloid leukemia: A report from the Children's Oncology Group. Pediatr Blood Cancer. 2021 Dec;68(12):e29281. doi: 10.1002/pbc.29281. Epub 2021 Oct 1. |
| 32029509 | Derived | Aplenc R, Meshinchi S, Sung L, Alonzo T, Choi J, Fisher B, Gerbing R, Hirsch B, Horton T, Kahwash S, Levine J, Loken M, Brodersen L, Pollard J, Raimondi S, Kolb EA, Gamis A. Bortezomib with standard chemotherapy for children with acute myeloid leukemia does not improve treatment outcomes: a report from the Children's Oncology Group. Haematologica. 2020 Jul;105(7):1879-1886. doi: 10.3324/haematol.2019.220962. Epub 2020 Feb 6. |
| 30987448 | Derived | Garcia-Pavia P, Kim Y, Restrepo-Cordoba MA, Lunde IG, Wakimoto H, Smith AM, Toepfer CN, Getz K, Gorham J, Patel P, Ito K, Willcox JA, Arany Z, Li J, Owens AT, Govind R, Nunez B, Mazaika E, Bayes-Genis A, Walsh R, Finkelman B, Lupon J, Whiffin N, Serrano I, Midwinter W, Wilk A, Bardaji A, Ingold N, Buchan R, Tayal U, Pascual-Figal DA, de Marvao A, Ahmad M, Garcia-Pinilla JM, Pantazis A, Dominguez F, John Baksi A, O'Regan DP, Rosen SD, Prasad SK, Lara-Pezzi E, Provencio M, Lyon AR, Alonso-Pulpon L, Cook SA, DePalma SR, Barton PJR, Aplenc R, Seidman JG, Ky B, Ware JS, Seidman CE. Genetic Variants Associated With Cancer Therapy-Induced Cardiomyopathy. Circulation. 2019 Jul 2;140(1):31-41. doi: 10.1161/CIRCULATIONAHA.118.037934. Epub 2019 Apr 16. |
| 30773463 | Derived | Lin KH, Xie A, Rutter JC, Ahn YR, Lloyd-Cowden JM, Nichols AG, Soderquist RS, Koves TR, Muoio DM, MacIver NJ, Lamba JK, Pardee TS, McCall CM, Rizzieri DA, Wood KC. Systematic Dissection of the Metabolic-Apoptotic Interface in AML Reveals Heme Biosynthesis to Be a Regulator of Drug Sensitivity. Cell Metab. 2019 May 7;29(5):1217-1231.e7. doi: 10.1016/j.cmet.2019.01.011. Epub 2019 Feb 14. |
| 28419486 | Derived | Hanley MJ, Mould DR, Taylor TJ, Gupta N, Suryanarayan K, Neuwirth R, Esseltine DL, Horton TM, Aplenc R, Alonzo TA, Lu X, Milton A, Venkatakrishnan K. Population Pharmacokinetic Analysis of Bortezomib in Pediatric Leukemia Patients: Model-Based Support for Body Surface Area-Based Dosing Over the 2- to 16-Year Age Range. J Clin Pharmacol. 2017 Sep;57(9):1183-1193. doi: 10.1002/jcph.906. Epub 2017 Apr 18. |
| FG001 | Arm B | IND I: Pts receive cytarabine IT and ADE chemotherapy as in Induction I, Arm A. Patients also receive bortezomib IV over 3-5 seconds on days 1, 4, 8. IND II: LR pts receive cytarabine IT, ADE chemotherapy, bortezomib as in IND I. HR pts receive cytarabine IT, MA as in IND II, Arm A (HR patients) and bortezomib IV on days 1, 4, 8. INT I: Pts receive cytarabine IT and AE in Arm A, Intensification II, and bortezomib IV on days 1, 4, 8. INT II: LR pts receive cytarabine IT on day 1, MA as in Arm A, IND II (HR patients), and bortezomib IV on days 1, 4, 8. HR pts with no donor for SCT receive high-dose cytarabine IV over 3 hours on days 1, 2, 8, 9 and asparaginase intramuscularly (IM) on days 2 and 9. SCT - Pts receive fludarabine phosphate IV over 30 minutes once daily on days -5 to -2 and busulfan IV over 2 hours 4 times daily on days -5 to -2.Pts undergo allogeneic SCT within 36 to 48 hours after the last dose of busulfan. Pts receive GVHD prophylaxis. |
| FG002 | Arm C (Cohort 1) | IND II: Pts receive cytarabine IT on day 1, cytarabine IV over 1-30 minutes on days 1-8, daunorubicin hydrochloride IV over 1-15 minutes on days 1, 3, and 5, etoposide IV over 1-2 hours on days 1-5, sorafenib tosylate PO on days 9-36. INT I: Pts receive cytarabine IT and AE chemotherapy in Arm A, Intensification II, and sorafenib tosylate PO on daily on days 6-28. INT II: Pts receive cytarabine IT on day 1, MA chemotherapy as in Arm A, Induction II (HR patients), sorafenib tosylate PO on days 7-34. SCT (HR patients with matched family [MFD] or unrelated donor): Pts receive fludarabine phosphate IV over 30 minutes once daily on days -5 to -2, busulfan IV over 2 hours 4 times daily on days -5 to -2. Patients undergo allogeneic SCT within 36 to 48 hours after the last dose of busulfan. Pts receive GVHD prophylaxis. MAINTENANCE: Pts receive sorafenib tosylate PO starting day 40-100 after INT II or SCT for one year. |
| FG003 | Arm C (Cohort 2) | IND I: Pts receive cytarabine IT & ADE as in Arm A, IND I & sorafenib tosylate PO at the time of known HR FLT3/ITD+ (including IND I & concurrently with chemo). IND II: Pts receive cytarabine IT day (d) 1, cytarabine IV over 1-30 minutes on d 1-8, daunorubicin hydrochloride IV over 1-15 minutes days 1, 3, 5, etoposide IV over 1-2 hours d 1-5, sorafenib tosylate PO d 9-36. INT I: Pts receive cytarabine IT and AE as in Arm A, INT II, and sorafenib tosylate PO on daily d 6-28. INT II: Pts receive cytarabine IT on d 1, MA as in Arm A, IND II (HR pts), sorafenib tosylate PO d 7-34. SCT (HR patients with matched family [MFD] or unrelated donor): Pts receive fludarabine phosphate IV over 30 minutes once daily on d -5 to -2, busulfan IV over 2 hours 4 times daily d -5 to -2. Pts undergo allogeneic SCT within 36-48 hours after last busulfan dose. Pts receive GVHD prophylaxis. MAINTENANCE: Pts receive sorafenib tosylate PO starting d 40-100 after INT II or SCT for 1 year. |
| FG004 | Arm C (Cohort 3) | IND I: Pts receive cytarabine IT & ADE as in Arm A, IND I & sorafenib tosylate PO days 11-28. IND II: Pts receive cytarabine IT day 1, cytarabine IV over 1-30 minutes on days 1-8, daunorubicin hydrochloride IV over 1-15 minutes days 1, 3, 5, etoposide IV over 1-2 hours days 1-5, sorafenib tosylate PO days 9-36. INT I: Pts receive cytarabine IT & AE as in Arm A, INT II, & sorafenib tosylate PO daily days 6-28. INT II: Pts receive cytarabine IT day 1, MA as in Arm A, IND II (HR patients), & sorafenib tosylate PO days 7-34. SCT (HR patients with matched family [MFD] or unrelated donor): Pts receive fludarabine phosphate IV over 30 minutes once daily on days -5 to -2 and busulfan IV over 2 hours 4 times daily days -5 to -2. Pts undergo allogeneic SCT within 36 to 48 hours after last busulfan dose. Pts receive GVHD prophylaxis. MAINTENANCE: Pts receive sorafenib tosylate PO starting day 40-100 after INT II or SCT for 1 year. |
| FG005 | Arm D | INDUCTION I: Patients with unknown FLT3/ITD status prior to study enrollment receive cytarabine IT and ADE chemotherapy as in Arm A, Induction I. If patients are determined to be HR FLT3/ITD+ no later than the end of Induction I they will be eligible to participate in Arm C. |
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| ID | Title | Description |
|---|---|---|
| BG000 | Arm A | INDUCTION (IND) 1Pts receive intrathecal (IT) cytarabine on day 1 and ADE with IV cytarabine over 1-30 minutes on days 1-10; daunorubicin hydrochloride IV over 1-15 minutes days1, 3, 5; etoposide IV 1-2 hours days1-5. IND IILow risk (LR) pts receive cytarabine IT and ADE chemotherapy as in INDI. High risk (HR) cytarabine IT day 1, MA chemo comprising high-dose cytarabine IV over 1-3 hours days1-4, mitoxantrone IV over 15-30 minutes days 3-6. INTENSIFICATION (INT) I: cytarabine IT day 1, AE chemo with high-dose cytarabine IV over 1-3 hours, etoposide IV over 1-2 hours days 1-5. INT II: LR-cytarabine IT day 1; Induction II MA chemo. HR and no SCT donor - high-dose cytarabine IV over 3 hours days1, 2, 8, 9; asparaginase intramuscularly (IM) days2,9. SCT: : pts receive fludarabine phosphate IV over 30 minutes once daily days -5 to -2, busulfan IV over 2 hours 4 times daily days -5 to -2. Allogeneic SCT within 36 to 48 hours after last busulfan dose. Pts receive GVHD prophylaxis. |
| BG001 | Arm B | IND I: Pts receive cytarabine IT and ADE chemotherapy as in Induction I, Arm A. Patients also receive bortezomib IV over 3-5 seconds on days 1, 4, 8. IND II: LR pts receive cytarabine IT, ADE chemotherapy, bortezomib as in IND I. HR pts receive cytarabine IT, MA as in IND II, Arm A (HR patients) and bortezomib IV on days 1, 4, 8. INT I: Pts receive cytarabine IT and AE in Arm A, Intensification II, and bortezomib IV on days 1, 4, 8. INT II: LR pts receive cytarabine IT on day 1, MA as in Arm A, IND II (HR patients), and bortezomib IV on days 1, 4, 8. HR pts with no donor for SCT receive high-dose cytarabine IV over 3 hours on days 1, 2, 8, 9 and asparaginase intramuscularly (IM) on days 2 and 9. SCT - Pts receive fludarabine phosphate IV over 30 minutes once daily on days -5 to -2 and busulfan IV over 2 hours 4 times daily on days -5 to -2.Pts undergo allogeneic SCT within 36 to 48 hours after the last dose of busulfan. Pts receive GVHD prophylaxis. |
| BG002 | Arm C (Cohort 1) | IND II: Pts receive cytarabine IT on day 1, cytarabine IV over 1-30 minutes on days 1-8, daunorubicin hydrochloride IV over 1-15 minutes on days 1, 3, and 5, etoposide IV over 1-2 hours on days 1-5, sorafenib tosylate PO on days 9-36. INT I: Pts receive cytarabine IT and AE chemotherapy in Arm A, Intensification II, and sorafenib tosylate PO on daily on days 6-28. INT II: Pts receive cytarabine IT on day 1, MA chemotherapy as in Arm A, Induction II (HR patients), sorafenib tosylate PO on days 7-34. SCT (HR patients with matched family [MFD] or unrelated donor): Pts receive fludarabine phosphate IV over 30 minutes once daily on days -5 to -2, busulfan IV over 2 hours 4 times daily on days -5 to -2. Patients undergo allogeneic SCT within 36 to 48 hours after the last dose of busulfan. Pts receive GVHD prophylaxis. MAINTENANCE: Pts receive sorafenib tosylate PO starting day 40-100 after INT II or SCT for one year. |
| BG003 | Arm C (Cohort 2) | IND I: Pts receive cytarabine IT & ADE as in Arm A, IND I & sorafenib tosylate PO at the time of known HR FLT3/ITD+ (including IND I & concurrently with chemo). IND II: Pts receive cytarabine IT day (d) 1, cytarabine IV over 1-30 minutes on d 1-8, daunorubicin hydrochloride IV over 1-15 minutes days 1, 3, 5, etoposide IV over 1-2 hours d 1-5, sorafenib tosylate PO d 9-36. INTE I: Pts receive cytarabine IT and AE in Arm A, INT II, and sorafenib tosylate PO on daily d 6-28. INT II: Pts receive cytarabine IT on d 1, MA as in Arm A, IND II (HR pts), sorafenib tosylate PO d 7-34. SCT (HR patients with matched family [MFD] or unrelated donor): Pts receive fludarabine phosphate IV over 30 minutes once daily on d -5 to -2, busulfan IV over 2 hours 4 times daily d -5 to -2. Pts undergo allogeneic SCT within 36-48 hours after last busulfan dose. Pts receive GVHD prophylaxis. MAINTENANCE: Pts receive sorafenib tosylate PO starting d 40-100 after INT II or SCT for 1 year. |
| BG004 | Arm C (Cohort 3) | IND I: Pts receive cytarabine IT & ADE as in Arm A, IND I & sorafenib tosylate PO days 11-28. IND II: Pts receive cytarabine IT day 1, cytarabine IV over 1-30 minutes on days 1-8, daunorubicin hydrochloride IV over 1-15 minutes days 1, 3, 5, etoposide IV over 1-2 hours days 1-5, sorafenib tosylate PO days 9-36. INT I: Pts receive cytarabine IT & AE as in Arm A, INT II, & sorafenib tosylate PO daily days 6-28. INT II: Pts receive cytarabine IT day 1, MA as in Arm A, IND II (HR patients), & sorafenib tosylate PO days 7-34. SCT (HR patients with matched family [MFD] or unrelated donor): Pts receive fludarabine phosphate IV over 30 minutes once daily on days -5 to -2 and busulfan IV over 2 hours 4 times daily days -5 to -2. Pts undergo allogeneic SCT within 36 to 48 hours after last busulfan dose. Pts receive GVHD prophylaxis. MAINTENANCE: Pts receive sorafenib tosylate PO starting day 40-100 after INT II or SCT for 1 year. |
| BG005 | Arm D | INDUCTION I: Patients with unknown FLT3/ITD status prior to study enrollment receive cytarabine IT and ADE chemotherapy as in Arm A, Induction I. If patients are determined to be HR FLT3/ITD+ no later than the end of Induction I they will be eligible to participate in Arm C. |
| BG006 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| Region of Enrollment | Number | participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Event-free Survival (EFS) for Patients Without High Allelic Ratio FLT3/ITD+ Mutations | The Kaplan-Meier method will be used to estimate 3-year EFS, defined as the time from study entry until induction failure, relapse, secondary malignancy, or death. | Patients ineligible, did not start treatment, or on Arm D are excluded from analyses of EFS. Arm D patients who were not eligible for Arm C by the end of induction I were declared off study per protocol; thus, no outcome data were collected for Arm D patients. Arms A and B are limited to patients without high allelic ratio FLT3/ITD+ mutations. | Posted | Number | 95% Confidence Interval | percentage of patients | Up to 3 years |
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| Primary | EFS for Patients on Arm C, Cohort 1 | The Kaplan-Meier method will be used to estimate 3-year EFS, defined as the time from study entry until induction failure, relapse, secondary malignancy, or death. | Patients ineligible, did not start treatment, or on Arm D are excluded from analyses of EFS. Arm D patients who were not eligible for Arm C by the end of induction I were declared off study per protocol; thus, no outcome data were collected for Arm D patients. | Posted | Number | 95% Confidence Interval | percentage of patients | Up to 3 years |
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| Primary | EFS for Patients on Arm C, Cohort 2 | The Kaplan-Meier method will be used to estimate 3-year EFS, defined as the time from study entry until induction failure, relapse, secondary malignancy, or death. | Patients ineligible, did not start treatment, or on Arm D are excluded from analyses of EFS. Arm D patients who were not eligible for Arm C by the end of induction I were declared off study per protocol; thus, no outcome data were collected for Arm D patients. | Posted | Number | 95% Confidence Interval | percentage of patients | Up to 3 years |
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| Primary | EFS for Patients on Arm C, Cohort 3 | The Kaplan-Meier method will be used to estimate 3-year EFS, defined as the time from study entry until induction failure, relapse, secondary malignancy, or death. | Patients ineligible, did not start treatment, or on Arm D are excluded from analyses of EFS. Arm D patients who were not eligible for Arm C by the end of induction I were declared off study per protocol; thus, no outcome data were collected for Arm D patients. | Posted | Number | 95% Confidence Interval | percentage of patients | Up to 3 years |
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| Secondary | Overall Survival (OS) for Patients Without High Allelic Ratio FLT3/ITD+ Mutations | The Kaplan-Meier method will be used to estimate 3-year OS, defined as the time from study entry until death. | Patients ineligible, did not start treatment, or on Arm D are excluded from analyses of OS. Arm D patients who were not eligible for Arm C by the end of induction I were declared off study per protocol; thus, no outcome data were collected for Arm D patients. Arms A and B are limited to patients without high allelic ratio FLT3/ITD+ mutations. | Posted | Number | 95% Confidence Interval | percentage of patients | Up to 3 years |
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| Secondary | OS for Patients on Arm C, Cohort 1 | The Kaplan-Meier method will be used to estimate 3-year OS, defined as the time from study entry until death. | Patients ineligible, did not start treatment, or on Arm D are excluded from analyses of OS. Arm D patients who were not eligible for Arm C by the end of induction I were declared off study per protocol; thus, no outcome data were collected for Arm D patients. | Posted | Number | 95% Confidence Interval | percentage of patients | Up to 3 years |
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| Secondary | OS for Patients on Arm C, Cohort 2 | The Kaplan-Meier method will be used to estimate 3-year OS, defined as the time from study entry until death. | Patients ineligible, did not start treatment, or on Arm D are excluded from analyses of OS. Arm D patients who were not eligible for Arm C by the end of induction I were declared off study per protocol; thus, no outcome data were collected for Arm D patients. | Posted | Number | 95% Confidence Interval | percentage of patients | Up to 3 years |
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| Secondary | OS for Patients on Arm C, Cohort 3 | The Kaplan-Meier method will be used to estimate 3-year OS, defined as the time from study entry until death. | Patients ineligible, did not start treatment, or on Arm D are excluded from analyses of OS. Arm D patients who were not eligible for Arm C by the end of induction I were declared off study per protocol; thus, no outcome data were collected for Arm D patients. | Posted | Number | 95% Confidence Interval | percentage of patients | Up to 3 years |
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| Secondary | Relapse Rate for Patients Without High Allelic Ratio FLT3/ITD+ Mutations | Cumulative incidence estimates 3 year relapse rate defined as time from study entry to induction failure or relapse where deaths or secondary malignancies are competing events. | Patients ineligible, did not start treatment, or on Arms C or D are excluded. Arm D patients who were not eligible for Arm C by the end of induction I were declared off study per protocol; thus, no outcome data were collected for Arm D patients. Results are limited to patients on Arms A and B without high allelic ratio FLT3/ITD+ mutations. | Posted | Number | 95% Confidence Interval | percentage of patients | Up to 3 years |
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| Secondary | Proportion of Patients Experiencing Grade 3 or Higher Non-hematologic Toxicities and Infections While on Protocol Therapy | The proportion of patients experiencing at least one grade 3 or higher non-hematologic toxicity and infection while on protocol therapy will be estimated along with the corresponding 95% confidence interval determined using a binomial exact method. Toxicity will be assessed by Common Terminology Criteria for Adverse Events version 4.0 (CTCAE v4.0). | Patients ineligible or who did not start treatment are excluded from results. | Posted | Number | 95% Confidence Interval | Proportion of patients | Up to 2 years |
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| Secondary | Proportion of High Risk Children Without HR FLT3/ITD+ Converting From Positive MRD at End of Induction I to Negative MRD at the End of Induction II | The proportion of high risk children without HR FLT3/ITD+ converting from positive MRD at end of Induction I to negative MRD at the end of Induction II will be estimated as well as the corresponding 95% confidence interval determined using a binomial exact method. | Patients ineligible, did not start treatment, on Arms C, D are excluded from results. Complete MRD results were not collected for Arm D patients due to being declared off study at end of induction I. Results limited to High Risk patients without high allelic ratio FLT3/ITD+ mutations and with evaluable MRD data from end of Induction I and II. | Posted | Number | 95% Confidence Interval | Proportion of patients | Up to 8 weeks |
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| Secondary | Total Scale Score From Parent-reported Pediatric Quality of Life Inventory Module | Results represent the total scale scores from the parent report of the PedsQLâ„¢ 4.0 Generic Core Scales for timepoint 1 (up to 14 days from start of therapy). Items are reverse-scored and linearly transformed to a 0-100 scale as follows: 0=100, 1=75, 2=50, 3=25, 4=0. Therefore, a higher number is a better outcome. The total score is the sum of all the items divided by the number of items answered on all the scales. "Scores on a scale" is used for a unit of measure. | Patients ineligible or who did not start treatment are excluded from results. Patients on Arms C (cohort 3) or Arm D are excluded due to enrolling post quality of life study accrual completion. Results are limited to only patients with an evaluable total scale score. | Posted | Mean | Inter-Quartile Range | Scores on a scale | Up to 14 days |
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| Secondary | Total Scale Score From Parent-reported Cancer Module | Results represent the total scale scores from the parent report of the PedsQLâ„¢ 3.0 Cancer Module for timepoint 1 (up to 14 days from start of therapy). Items are reverse-scored and linearly transformed to a 0-100 scale as follows: 0=100, 1=75, 2=50, 3=25, 4=0. Therefore, a higher number is a better outcome. The total score is the sum of all the items divided by the number of items answered on all the scales. "Scores on a scale" is used for a unit of measure. | Patients ineligible or who did not start treatment are excluded from results. Patients on Arms C (cohort 3) or Arm D are excluded due to enrolling post quality of life study accrual completion. Results are limited to only patients with an evaluable total scale score. | Posted | Mean | Inter-Quartile Range | Scores on a scale | Up to 14 days |
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| Secondary | Total Scale Score From Parent-reported Multidimensional Fatigue Scale Module | Results represent the total scale scores from the parent report of the PedsQLâ„¢ Multidimensional Fatigue Scale for timepoint 1 (up to 14 days from start of therapy). Items are reverse-scored and linearly transformed to a 0-100 scale as follows: 0=100, 1=75, 2=50, 3=25, 4=0. Therefore, a higher number is a better outcome. The total score is the sum of all the items divided by the number of items answered on all the scales. "Scores on a scale" is used for a unit of measure. | Patients ineligible or who did not start treatment are excluded from results. Patients on Arms C (cohort 3) or Arm D are excluded due to enrolling post quality of life study accrual completion. Results are limited to only patients with an evaluable total scale score. | Posted | Mean | Inter-Quartile Range | Scores on a scale | Up to 14 days |
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| Secondary | Bortezomib Clearance | Median and range of bortezomib clearance during Induction II. | Only eligible patients on Arm B with evaluable Bortezomib PK clearance data during Induction II are reported. | Posted | Median | Full Range | Liters/hour/m^2 | Day 8 of Induction II |
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| Secondary | Sorafenib Steady State Concentration | Median and range of sorafenib steady state concentration for Induction I. | Data reported from Arm C were collected and analyzed regardless of the cohort as pre-specified in the study protocol. Only eligible patients on Arm C with evaluable Sorafenib steady state concentration data during Induction I are reported. | Posted | Median | Full Range | Nanogram/Milliliter | Up to 30 days |
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| Secondary | Change in Shortening Fraction | Mean percentage change in shortening fraction from baseline to the end of Induction I will be determined for eligible patients enrolled on Arms A, B and C. | Patients ineligible, did not start treatment, or on Arm D are excluded from results. Shortening fraction data were not collected at end of Induction I for patients enrolled to Arm D. Results are limited to patients with evaluable shortening fraction data from study entry and at end of Induction I . | Posted | Mean | Standard Error | Percentage change | Up to 4 weeks |
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| Secondary | Change in Ejection Fraction | The mean percentage change in ejection fraction from baseline to the end of Induction I will be determined for eligible patients enrolled on Arms A, B and C. | Patients ineligible, did not start treatment, or on Arm D are excluded from results. Ejection fraction data were not collected at end of Induction I for patients enrolled to Arm D. Results are limited to patients with evaluable ejection fraction data from study entry and at end of Induction I . | Posted | Mean | Standard Deviation | Percentage change | Up to 4 weeks |
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| Secondary | Serum Concentrations of GVHD Biomarker | The mean serum concentration of the day 28 GVHD biomarker will be estimated as well as the corresponding 95% confidence interval. | Data were never collected | Posted | Up to day 28 after SCT |
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| Other Pre-specified | Course Duration | Descriptive statistics will be used to summarize length of hospitalization time. | Not Posted | Up to 6 months | Participants | ||||||||||||||||||||||||||||||||||
| Other Pre-specified | Incidence of Treatment-related Mortality | Cumulative incidence estimates that account for competing events will be used to estimate treatment-related mortality. | Not Posted | Up to 2 years | Participants | ||||||||||||||||||||||||||||||||||
| Other Pre-specified | Length of Hospitalization | Descriptive statistics will be used to summarize length of hospitalization time. | Not Posted | Up to 6 months | Participants | ||||||||||||||||||||||||||||||||||
| Other Pre-specified | Remission Rate After 1 Course of Therapy | The proportion of patients achieving remission after 1 course of therapy will be estimated along with a corresponding 95% confidence interval. | Not Posted | 4 weeks | Participants | ||||||||||||||||||||||||||||||||||
| Other Pre-specified | Remission Rate After 2 Courses of Therapy | The proportion of patients achieving remission after 2 courses of therapy will be estimated along with a corresponding 95% confidence interval. | Not Posted | 8 weeks | Participants | ||||||||||||||||||||||||||||||||||
| Other Pre-specified | Time to Blood Count Recovery | Cumulative incidence estimates that account for competing events will be used to estimate time to count recovery. | Not Posted | Up to 6 months | Participants |
While patients were on protocol therapy (including up to 4 courses, stem cell transplant course, and 3 courses of maintenance therapy)) or up to 7 years in follow-up.
Adverse event reporting is collected routinely using case report forms. The SAE table reflects NCI Common Terminology Criteria for Adverse Events (CTCAEs) submitted by the institution via expedited reporting (NCI AdEERs / CAeRs). All remaining CTCAEs collected by means other than expedited reporting are non-serious and are reported in the "AE Other" table. Ineligible patients are excluded from reporting of adverse events. All-Cause Mortality includes all deaths collected on the study.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Arm A | INDUCTION (IND) 1Pts receive intrathecal (IT) cytarabine on day 1 and ADE with IV cytarabine over 1-30 minutes on days 1-10; daunorubicin hydrochloride IV over 1-15 minutes days1, 3, 5; etoposide IV 1-2 hours days1-5. IND IILow risk (LR) pts receive cytarabine IT and ADE chemotherapy as in INDI. High risk (HR) cytarabine IT day 1, MA chemo comprising high-dose cytarabine IV over 1-3 hours days1-4, mitoxantrone IV over 15-30 minutes days 3-6. INTENSIFICATION (INT) I: cytarabine IT day 1, AE chemo with high-dose cytarabine IV over 1-3 hours, etoposide IV over 1-2 hours days 1-5. INT II: LR-cytarabine IT day 1; Induction II MA chemo. HR and no SCT donor - high-dose cytarabine IV over 3 hours days1, 2, 8, 9; asparaginase intramuscularly (IM) days2,9. SCT: : pts receive fludarabine phosphate IV over 30 minutes once daily days -5 to -2, busulfan IV over 2 hours 4 times daily days -5 to -2. Allogeneic SCT within 36 to 48 hours after last busulfan dose. Pts receive GVHD prophylaxis. | 198 | 559 | 82 | 559 | 506 | 559 |
| EG001 | Arm B | IND I: Pts receive cytarabine IT and ADE chemotherapy as in Induction I, Arm A. Patients also receive bortezomib IV over 3-5 seconds on days 1, 4, 8. IND II: LR pts receive cytarabine IT, ADE chemotherapy, bortezomib as in IND I. HR pts receive cytarabine IT, MA as in IND II, Arm A (HR patients) and bortezomib IV on days 1, 4, 8. INT I: Pts receive cytarabine IT and AE in Arm A, Intensification II, and bortezomib IV on days 1, 4, 8. INT II: LR pts receive cytarabine IT on day 1, MA as in Arm A, IND II (HR patients), and bortezomib IV on days 1, 4, 8. HR pts with no donor for SCT receive high-dose cytarabine IV over 3 hours on days 1, 2, 8, 9 and asparaginase intramuscularly (IM) on days 2 and 9. SCT - Pts receive fludarabine phosphate IV over 30 minutes once daily on days -5 to -2 and busulfan IV over 2 hours 4 times daily on days -5 to -2.Pts undergo allogeneic SCT within 36 to 48 hours after the last dose of busulfan. Pts receive GVHD prophylaxis. | 189 | 575 | 305 | 575 | 529 | 575 |
| EG002 | Arm C (Cohort 1) | IND II: Pts receive cytarabine IT on day 1, cytarabine IV over 1-30 minutes on days 1-8, daunorubicin hydrochloride IV over 1-15 minutes on days 1, 3, and 5, etoposide IV over 1-2 hours on days 1-5, sorafenib tosylate PO on days 9-36. INT I: Pts receive cytarabine IT and AE chemotherapy in Arm A, Intensification II, and sorafenib tosylate PO on daily on days 6-28. INT II: Pts receive cytarabine IT on day 1, MA chemotherapy as in Arm A, Induction II (HR patients), sorafenib tosylate PO on days 7-34. SCT (HR patients with matched family [MFD] or unrelated donor): Pts receive fludarabine phosphate IV over 30 minutes once daily on days -5 to -2, busulfan IV over 2 hours 4 times daily on days -5 to -2. Patients undergo allogeneic SCT within 36 to 48 hours after the last dose of busulfan. Pts receive GVHD prophylaxis. MAINTENANCE: Pts receive sorafenib tosylate PO starting day 40-100 after INT II or SCT for one year. | 7 | 12 | 6 | 12 | 12 | 12 |
| EG003 | Arm C (Cohort 2) | IND I: Pts receive cytarabine IT & ADE as in Arm A, IND I & sorafenib tosylate PO at the time of known HR FLT3/ITD+ (including IND I & concurrently with chemo). IND II: Pts receive cytarabine IT day (d) 1, cytarabine IV over 1-30 minutes on d 1-8, daunorubicin hydrochloride IV over 1-15 minutes days 1, 3, 5, etoposide IV over 1-2 hours d 1-5, sorafenib tosylate PO d 9-36. INTE I: Pts receive cytarabine IT and AE in Arm A, INT II, and sorafenib tosylate PO on daily d 6-28. INT II: Pts receive cytarabine IT on d 1, MA as in Arm A, IND II (HR pts), sorafenib tosylate PO d 7-34. SCT (HR patients with matched family [MFD] or unrelated donor): Pts receive fludarabine phosphate IV over 30 minutes once daily on d -5 to -2, busulfan IV over 2 hours 4 times daily d -5 to -2. Pts undergo allogeneic SCT within 36-48 hours after last busulfan dose. Pts receive GVHD prophylaxis. MAINTENANCE: Pts receive sorafenib tosylate PO starting d 40-100 after INT II or SCT for 1 year. | 11 | 33 | 16 | 33 | 32 | 33 |
| EG004 | Arm C (Cohort 3) | IND I: Pts receive cytarabine IT & ADE as in Arm A, IND I & sorafenib tosylate PO days 11-28. IND II: Pts receive cytarabine IT day 1, cytarabine IV over 1-30 minutes on days 1-8, daunorubicin hydrochloride IV over 1-15 minutes days 1, 3, 5, etoposide IV over 1-2 hours days 1-5, sorafenib tosylate PO days 9-36. INT I: Pts receive cytarabine IT & AE cin Arm A, INT II, & sorafenib tosylate PO daily days 6-28. INT II: Pts receive cytarabine IT day 1, MA as in Arm A, IND II (HR patients), & sorafenib tosylate PO days 7-34. SCT (HR patients with matched family [MFD] or unrelated donor): Pts receive fludarabine phosphate IV over 30 minutes once daily on days -5 to -2 and busulfan IV over 2 hours 4 times daily days -5 to -2. Pts undergo allogeneic SCT within 36 to 48 hours after last busulfan dose. Pts receive GVHD prophylaxis. MAINTENANCE: Pts receive sorafenib tosylate PO starting day 40-100 after INT II or SCT for 1 year. | 16 | 47 | 30 | 47 | 41 | 47 |
| EG005 | Arm D | INDUCTION I: Patients with unknown FLT3/ITD status prior to study enrollment receive cytarabine IT and ADE chemotherapy as in Arm A, Induction I. If patients are determined to be HR FLT3/ITD+ no later than the end of Induction I they will be eligible to participate in Arm C. | 2 | 376 | 2 | 376 | 7 | 376 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anemia | Blood and lymphatic system disorders | Systematic Assessment | Adeers submitted |
| |
| Blood and lymphatic system disorders - Other, specify | Blood and lymphatic system disorders | Systematic Assessment | Adeers submitted |
| |
| Bone marrow hypocellular | Blood and lymphatic system disorders | Systematic Assessment | Adeers submitted |
| |
| Disseminated intravascular coagulation | Blood and lymphatic system disorders | Systematic Assessment | Adeers submitted |
| |
| Febrile neutropenia | Blood and lymphatic system disorders | Systematic Assessment | Adeers submitted |
| |
| Hemolysis | Blood and lymphatic system disorders | Systematic Assessment | Adeers submitted |
| |
| Hemolytic uremic syndrome | Blood and lymphatic system disorders | Systematic Assessment | Adeers submitted |
| |
| Leukocytosis | Blood and lymphatic system disorders | Systematic Assessment | Adeers submitted |
| |
| Asystole | Cardiac disorders | Systematic Assessment | Adeers submitted |
| |
| Atrial fibrillation | Cardiac disorders | Systematic Assessment | Adeers submitted |
| |
| Atrial flutter | Cardiac disorders | Systematic Assessment | Adeers submitted |
| |
| Cardiac arrest | Cardiac disorders | Systematic Assessment | Adeers submitted |
| |
| Cardiac disorders - Other, specify | Cardiac disorders | Systematic Assessment | Adeers submitted |
| |
| Chest pain - cardiac | Cardiac disorders | Systematic Assessment | Adeers submitted |
| |
| Heart failure | Cardiac disorders | Systematic Assessment | Adeers submitted |
| |
| Left ventricular systolic dysfunction | Cardiac disorders | Systematic Assessment | Adeers submitted |
| |
| Myocardial infarction | Cardiac disorders | Systematic Assessment | Adeers submitted |
| |
| Pericardial effusion | Cardiac disorders | Systematic Assessment | Adeers submitted |
| |
| Pericarditis | Cardiac disorders | Systematic Assessment | Adeers submitted |
| |
| Restrictive cardiomyopathy | Cardiac disorders | Systematic Assessment | Adeers submitted |
| |
| Right ventricular dysfunction | Cardiac disorders | Systematic Assessment | Adeers submitted |
| |
| Sinus bradycardia | Cardiac disorders | Systematic Assessment | Adeers submitted |
| |
| Sinus tachycardia | Cardiac disorders | Systematic Assessment | Adeers submitted |
| |
| Supraventricular tachycardia | Cardiac disorders | Systematic Assessment | Adeers submitted |
| |
| Ventricular arrhythmia | Cardiac disorders | Systematic Assessment | Adeers submitted |
| |
| Ventricular fibrillation | Cardiac disorders | Systematic Assessment | Adeers submitted |
| |
| Ventricular tachycardia | Cardiac disorders | Systematic Assessment | Adeers submitted |
| |
| Adrenal insufficiency | Endocrine disorders | Systematic Assessment | Adeers submitted |
| |
| Endocrine disorders - Other, specify | Endocrine disorders | Systematic Assessment | Adeers submitted |
| |
| Hypothyroidism | Endocrine disorders | Systematic Assessment | Adeers submitted |
| |
| Eye disorders - Other, specify | Eye disorders | Systematic Assessment | Adeers submitted |
| |
| Optic nerve disorder | Eye disorders | Systematic Assessment | Adeers submitted |
| |
| Papilledema | Eye disorders | Systematic Assessment | Adeers submitted |
| |
| Abdominal distension | Gastrointestinal disorders | Systematic Assessment | Adeers submitted |
| |
| Abdominal pain | Gastrointestinal disorders | Systematic Assessment | Adeers submitted |
| |
| Anal pain | Gastrointestinal disorders | Systematic Assessment | Adeers submitted |
| |
| Ascites | Gastrointestinal disorders | Systematic Assessment | Adeers submitted |
| |
| Colitis | Gastrointestinal disorders | Systematic Assessment | Adeers submitted |
| |
| Colonic perforation | Gastrointestinal disorders | Systematic Assessment | Adeers submitted |
| |
| Diarrhea | Gastrointestinal disorders | Systematic Assessment | Adeers submitted |
| |
| Enterocolitis | Gastrointestinal disorders | Systematic Assessment | Adeers submitted |
| |
| Esophagitis | Gastrointestinal disorders | Systematic Assessment | Adeers submitted |
| |
| Gastric hemorrhage | Gastrointestinal disorders | Systematic Assessment | Adeers submitted |
| |
| Gastritis | Gastrointestinal disorders | Systematic Assessment | Adeers submitted |
| |
| Gastrointestinal disorders - Other, specify | Gastrointestinal disorders | Systematic Assessment | Adeers submitted |
| |
| Ileus | Gastrointestinal disorders | Systematic Assessment | Adeers submitted |
| |
| Lower gastrointestinal hemorrhage | Gastrointestinal disorders | Systematic Assessment | Adeers submitted |
| |
| Mucositis oral | Gastrointestinal disorders | Systematic Assessment | Adeers submitted |
| |
| Nausea | Gastrointestinal disorders | Systematic Assessment | Adeers submitted |
| |
| Oral pain | Gastrointestinal disorders | Systematic Assessment | Adeers submitted |
| |
| Pancreatitis | Gastrointestinal disorders | Systematic Assessment | Adeers submitted |
| |
| Small intestinal obstruction | Gastrointestinal disorders | Systematic Assessment | Adeers submitted |
| |
| Typhlitis | Gastrointestinal disorders | Systematic Assessment | Adeers submitted |
| |
| Upper gastrointestinal hemorrhage | Gastrointestinal disorders | Systematic Assessment | Adeers submitted |
| |
| Vomiting | Gastrointestinal disorders | Systematic Assessment | Adeers submitted |
| |
| Chills | General disorders | Systematic Assessment | Adeers submitted |
| |
| Death NOS | General disorders | Systematic Assessment | Adeers submitted |
| |
| Edema face | General disorders | Systematic Assessment | Adeers submitted |
| |
| Fever | General disorders | Systematic Assessment | Adeers submitted |
| |
| Gait disturbance | General disorders | Systematic Assessment | Adeers submitted |
| |
| Hypothermia | General disorders | Systematic Assessment | Adeers submitted |
| |
| Multi-organ failure | General disorders | Systematic Assessment | Adeers submitted |
| |
| Non-cardiac chest pain | General disorders | Systematic Assessment | Adeers submitted |
| |
| Pain | General disorders | Systematic Assessment | Adeers submitted |
| |
| Bile duct stenosis | Hepatobiliary disorders | Systematic Assessment | Adeers submitted |
| |
| Cholecystitis | Hepatobiliary disorders | Systematic Assessment | Adeers submitted |
| |
| Hepatic failure | Hepatobiliary disorders | Systematic Assessment | Adeers submitted |
| |
| Hepatobiliary disorders - Other, specify | Hepatobiliary disorders | Systematic Assessment | Adeers submitted |
| |
| Allergic reaction | Immune system disorders | Systematic Assessment | Adeers submitted |
| |
| Anaphylaxis | Immune system disorders | Systematic Assessment | Adeers submitted |
| |
| Immune system disorders - Other, specify | Immune system disorders | Systematic Assessment | Adeers submitted |
| |
| Anorectal infection | Infections and infestations | Systematic Assessment | Adeers submitted |
| |
| Appendicitis | Infections and infestations | Systematic Assessment | Adeers submitted |
| |
| Bladder infection | Infections and infestations | Systematic Assessment | Adeers submitted |
| |
| Bronchial infection | Infections and infestations | Systematic Assessment | Adeers submitted |
| |
| Catheter related infection | Infections and infestations | Systematic Assessment | Adeers submitted |
| |
| Cecal infection | Infections and infestations | Systematic Assessment | Adeers submitted |
| |
| Duodenal infection | Infections and infestations | Systematic Assessment | Adeers submitted |
| |
| Encephalitis infection | Infections and infestations | Systematic Assessment | Adeers submitted |
| |
| Enterocolitis infectious | Infections and infestations | Systematic Assessment | Adeers submitted |
| |
| Esophageal infection | Infections and infestations | Systematic Assessment | Adeers submitted |
| |
| Infections and infestations - Other, specify | Infections and infestations | Systematic Assessment | Adeers submitted |
| |
| Lung infection | Infections and infestations | Systematic Assessment | Adeers submitted |
| |
| Lymph gland infection | Infections and infestations | Systematic Assessment | Adeers submitted |
| |
| Meningitis | Infections and infestations | Systematic Assessment | Adeers submitted |
| |
| Mucosal infection | Infections and infestations | Systematic Assessment | Adeers submitted |
| |
| Periorbital infection | Infections and infestations | Systematic Assessment | Adeers submitted |
| |
| Sepsis | Infections and infestations | Systematic Assessment | Adeers submitted |
| |
| Skin infection | Infections and infestations | Systematic Assessment | Adeers submitted |
| |
| Soft tissue infection | Infections and infestations | Systematic Assessment | Adeers submitted |
| |
| Tracheitis | Infections and infestations | Systematic Assessment | Adeers submitted |
| |
| Upper respiratory infection | Infections and infestations | Systematic Assessment | Adeers submitted |
| |
| Urinary tract infection | Infections and infestations | Systematic Assessment | Adeers submitted |
| |
| Infusion related reaction | Injury, poisoning and procedural complications | Systematic Assessment | Adeers submitted |
| |
| Postoperative hemorrhage | Injury, poisoning and procedural complications | Systematic Assessment | Adeers submitted |
| |
| Vascular access complication | Injury, poisoning and procedural complications | Systematic Assessment | Adeers submitted |
| |
| Activated partial thromboplastin time prolonged | Investigations | Systematic Assessment | Adeers submitted |
| |
| Alanine aminotransferase increased | Investigations | Systematic Assessment | Adeers submitted |
| |
| Aspartate aminotransferase increased | Investigations | Systematic Assessment | Adeers submitted |
| |
| Blood bilirubin increased | Investigations | Systematic Assessment | Adeers submitted |
| |
| Carbon monoxide diffusing capacity decreased | Investigations | Systematic Assessment | Adeers submitted |
| |
| Creatinine increased | Investigations | Systematic Assessment | Adeers submitted |
| |
| Ejection fraction decreased | Investigations | Systematic Assessment | Adeers submitted |
| |
| Electrocardiogram QT corrected interval prolonged | Investigations | Systematic Assessment | Adeers submitted |
| |
| Fibrinogen decreased | Investigations | Systematic Assessment | Adeers submitted |
| |
| GGT increased | Investigations | Systematic Assessment | Adeers submitted |
| |
| Investigations - Other, specify | Investigations | Systematic Assessment | Adeers submitted |
| |
| Lipase increased | Investigations | Systematic Assessment | Adeers submitted |
| |
| Lymphocyte count decreased | Investigations | Systematic Assessment | Adeers submitted |
| |
| Neutrophil count decreased | Investigations | Systematic Assessment | Adeers submitted |
| |
| Platelet count decreased | Investigations | Systematic Assessment | Adeers submitted |
| |
| Serum amylase increased | Investigations | Systematic Assessment | Adeers submitted |
| |
| Urine output decreased | Investigations | Systematic Assessment | Adeers submitted |
| |
| Weight loss | Investigations | Systematic Assessment | Adeers submitted |
| |
| White blood cell decreased | Investigations | Systematic Assessment | Adeers submitted |
| |
| Acidosis | Metabolism and nutrition disorders | Systematic Assessment | Adeers submitted |
| |
| Alkalosis | Metabolism and nutrition disorders | Systematic Assessment | Adeers submitted |
| |
| Anorexia | Metabolism and nutrition disorders | Systematic Assessment | Adeers submitted |
| |
| Dehydration | Metabolism and nutrition disorders | Systematic Assessment | Adeers submitted |
| |
| Hypercalcemia | Metabolism and nutrition disorders | Systematic Assessment | Adeers submitted |
| |
| Hyperglycemia | Metabolism and nutrition disorders | Systematic Assessment | Adeers submitted |
| |
| Hyperkalemia | Metabolism and nutrition disorders | Systematic Assessment | Adeers submitted |
| |
| Hypernatremia | Metabolism and nutrition disorders | Systematic Assessment | Adeers submitted |
| |
| Hypertriglyceridemia | Metabolism and nutrition disorders | Systematic Assessment | Adeers submitted |
| |
| Hypoalbuminemia | Metabolism and nutrition disorders | Systematic Assessment | Adeers submitted |
| |
| Hypocalcemia | Metabolism and nutrition disorders | Systematic Assessment | Adeers submitted |
| |
| Hypokalemia | Metabolism and nutrition disorders | Systematic Assessment | Adeers submitted |
| |
| Hypomagnesemia | Metabolism and nutrition disorders | Systematic Assessment | Adeers submitted |
| |
| Hyponatremia | Metabolism and nutrition disorders | Systematic Assessment | Adeers submitted |
| |
| Hypophosphatemia | Metabolism and nutrition disorders | Systematic Assessment | Adeers submitted |
| |
| Metabolism and nutrition disorders - Other, specify | Metabolism and nutrition disorders | Systematic Assessment | Adeers submitted |
| |
| Tumor lysis syndrome | Metabolism and nutrition disorders | Systematic Assessment | Adeers submitted |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | Systematic Assessment | Adeers submitted |
| |
| Back pain | Musculoskeletal and connective tissue disorders | Systematic Assessment | Adeers submitted |
| |
| Neck pain | Musculoskeletal and connective tissue disorders | Systematic Assessment | Adeers submitted |
| |
| Pain in extremity | Musculoskeletal and connective tissue disorders | Systematic Assessment | Adeers submitted |
| |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | Systematic Assessment | Adeers submitted |
| |
| Ataxia | Nervous system disorders | Systematic Assessment | Adeers submitted |
| |
| Central nervous system necrosis | Nervous system disorders | Systematic Assessment | Adeers submitted |
| |
| Cerebrospinal fluid leakage | Nervous system disorders | Systematic Assessment | Adeers submitted |
| |
| Cognitive disturbance | Nervous system disorders | Systematic Assessment | Adeers submitted |
| |
| Depressed level of consciousness | Nervous system disorders | Systematic Assessment | Adeers submitted |
| |
| Dizziness | Nervous system disorders | Systematic Assessment | Adeers submitted |
| |
| Dysesthesia | Nervous system disorders | Systematic Assessment | Adeers submitted |
| |
| Edema cerebral | Nervous system disorders | Systematic Assessment | Adeers submitted |
| |
| Encephalopathy | Nervous system disorders | Systematic Assessment | Adeers submitted |
| |
| Headache | Nervous system disorders | Systematic Assessment | Adeers submitted |
| |
| Hydrocephalus | Nervous system disorders | Systematic Assessment | Adeers submitted |
| |
| Hypersomnia | Nervous system disorders | Systematic Assessment | Adeers submitted |
| |
| Intracranial hemorrhage | Nervous system disorders | Systematic Assessment | Adeers submitted |
| |
| Leukoencephalopathy | Nervous system disorders | Systematic Assessment | Adeers submitted |
| |
| Nervous system disorders - Other, specify | Nervous system disorders | Systematic Assessment | Adeers submitted |
| |
| Neuralgia | Nervous system disorders | Systematic Assessment | Adeers submitted |
| |
| Paresthesia | Nervous system disorders | Systematic Assessment | Adeers submitted |
| |
| Peripheral sensory neuropathy | Nervous system disorders | Systematic Assessment | Adeers submitted |
| |
| Reversible posterior leukoencephalopathy syndrome | Nervous system disorders | Systematic Assessment | Adeers submitted |
| |
| Seizure | Nervous system disorders | Systematic Assessment | Adeers submitted |
| |
| Somnolence | Nervous system disorders | Systematic Assessment | Adeers submitted |
| |
| Syncope | Nervous system disorders | Systematic Assessment | Adeers submitted |
| |
| Agitation | Psychiatric disorders | Systematic Assessment | Adeers submitted |
| |
| Anxiety | Psychiatric disorders | Systematic Assessment | Adeers submitted |
| |
| Delirium | Psychiatric disorders | Systematic Assessment | Adeers submitted |
| |
| Acute kidney injury | Renal and urinary disorders | Systematic Assessment | Adeers submitted |
| |
| Cystitis noninfective | Renal and urinary disorders | Systematic Assessment | Adeers submitted |
| |
| Hematuria | Renal and urinary disorders | Systematic Assessment | Adeers submitted |
| |
| Proteinuria | Renal and urinary disorders | Systematic Assessment | Adeers submitted |
| |
| Renal and urinary disorders - Other, specify | Renal and urinary disorders | Systematic Assessment | Adeers submitted |
| |
| Adult respiratory distress syndrome | Respiratory, thoracic and mediastinal disorders | Systematic Assessment | Adeers submitted |
| |
| Apnea | Respiratory, thoracic and mediastinal disorders | Systematic Assessment | Adeers submitted |
| |
| Aspiration | Respiratory, thoracic and mediastinal disorders | Systematic Assessment | Adeers submitted |
| |
| Atelectasis | Respiratory, thoracic and mediastinal disorders | Systematic Assessment | Adeers submitted |
| |
| Bronchopulmonary hemorrhage | Respiratory, thoracic and mediastinal disorders | Systematic Assessment | Adeers submitted |
| |
| Bronchospasm | Respiratory, thoracic and mediastinal disorders | Systematic Assessment | Adeers submitted |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | Systematic Assessment | Adeers submitted |
| |
| Dyspnea | Respiratory, thoracic and mediastinal disorders | Systematic Assessment | Adeers submitted |
| |
| Epistaxis | Respiratory, thoracic and mediastinal disorders | Systematic Assessment | Adeers submitted |
| |
| Hypoxia | Respiratory, thoracic and mediastinal disorders | Systematic Assessment | Adeers submitted |
| |
| Laryngeal edema | Respiratory, thoracic and mediastinal disorders | Systematic Assessment | Adeers submitted |
| |
| Laryngeal mucositis | Respiratory, thoracic and mediastinal disorders | Systematic Assessment | Adeers submitted |
| |
| Mediastinal hemorrhage | Respiratory, thoracic and mediastinal disorders | Systematic Assessment | Adeers submitted |
| |
| Pharyngeal mucositis | Respiratory, thoracic and mediastinal disorders | Systematic Assessment | Adeers submitted |
| |
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | Systematic Assessment | Adeers submitted |
| |
| Pneumonitis | Respiratory, thoracic and mediastinal disorders | Systematic Assessment | Adeers submitted |
| |
| Productive cough | Respiratory, thoracic and mediastinal disorders | Systematic Assessment | Adeers submitted |
| |
| Pulmonary edema | Respiratory, thoracic and mediastinal disorders | Systematic Assessment | Adeers submitted |
| |
| Pulmonary hypertension | Respiratory, thoracic and mediastinal disorders | Systematic Assessment | Adeers submitted |
| |
| Respiratory failure | Respiratory, thoracic and mediastinal disorders | Systematic Assessment | Adeers submitted |
| |
| Respiratory, thoracic and mediastinal disorders - Other, specify | Respiratory, thoracic and mediastinal disorders | Systematic Assessment | Adeers submitted |
| |
| Sore throat | Respiratory, thoracic and mediastinal disorders | Systematic Assessment | Adeers submitted |
| |
| Stridor | Respiratory, thoracic and mediastinal disorders | Systematic Assessment | Adeers submitted |
| |
| Tracheal mucositis | Respiratory, thoracic and mediastinal disorders | Systematic Assessment | Adeers submitted |
| |
| Wheezing | Respiratory, thoracic and mediastinal disorders | Systematic Assessment | Adeers submitted |
| |
| Erythroderma | Skin and subcutaneous tissue disorders | Systematic Assessment | Adeers submitted |
| |
| Pain of skin | Skin and subcutaneous tissue disorders | Systematic Assessment | Adeers submitted |
| |
| Palmar-plantar erythrodysesthesia syndrome | Skin and subcutaneous tissue disorders | Systematic Assessment | Adeers submitted |
| |
| Pruritus | Skin and subcutaneous tissue disorders | Systematic Assessment | Adeers submitted |
| |
| Rash maculo-papular | Skin and subcutaneous tissue disorders | Systematic Assessment | Adeers submitted |
| |
| Skin and subcutaneous tissue disorders - Other, specify | Skin and subcutaneous tissue disorders | Systematic Assessment | Adeers submitted |
| |
| Toxic epidermal necrolysis | Skin and subcutaneous tissue disorders | Systematic Assessment | Adeers submitted |
| |
| Urticaria | Skin and subcutaneous tissue disorders | Systematic Assessment | Adeers submitted |
| |
| Capillary leak syndrome | Vascular disorders | Systematic Assessment | Adeers submitted |
| |
| Flushing | Vascular disorders | Systematic Assessment | Adeers submitted |
| |
| Hypertension | Vascular disorders | Systematic Assessment | Adeers submitted |
| |
| Hypotension | Vascular disorders | Systematic Assessment | Adeers submitted |
| |
| Peripheral ischemia | Vascular disorders | Systematic Assessment | Adeers submitted |
| |
| Thromboembolic event | Vascular disorders | Systematic Assessment | Adeers submitted |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anemia | Blood and lymphatic system disorders | Systematic Assessment | Adeers not subm |
| |
| Blood and lymphatic system disorders - Other, specify | Blood and lymphatic system disorders | Systematic Assessment | Adeers not subm |
| |
| Bone marrow hypocellular | Blood and lymphatic system disorders | Systematic Assessment | Adeers not subm |
| |
| Disseminated intravascular coagulation | Blood and lymphatic system disorders | Systematic Assessment | Adeers not subm |
| |
| Febrile neutropenia | Blood and lymphatic system disorders | Systematic Assessment | Adeers not subm |
| |
| Leukocytosis | Blood and lymphatic system disorders | Systematic Assessment | Adeers not subm |
| |
| Lymph node pain | Blood and lymphatic system disorders | Systematic Assessment | Adeers not subm |
| |
| Thrombotic thrombocytopenic purpura | Blood and lymphatic system disorders | Systematic Assessment | Adeers not subm |
| |
| Asystole | Cardiac disorders | Systematic Assessment | Adeers not subm |
| |
| Cardiac arrest | Cardiac disorders | Systematic Assessment | Adeers not subm |
| |
| Cardiac disorders - Other, specify | Cardiac disorders | Systematic Assessment | Adeers not subm |
| |
| Chest pain - cardiac | Cardiac disorders | Systematic Assessment | Adeers not subm |
| |
| Heart failure | Cardiac disorders | Systematic Assessment | Adeers not subm |
| |
| Left ventricular systolic dysfunction | Cardiac disorders | Systematic Assessment | Adeers not subm |
| |
| Pericardial effusion | Cardiac disorders | Systematic Assessment | Adeers not subm |
| |
| Pulmonary valve disease | Cardiac disorders | Systematic Assessment | Adeers not subm |
| |
| Restrictive cardiomyopathy | Cardiac disorders | Systematic Assessment | Adeers not subm |
| |
| Right ventricular dysfunction | Cardiac disorders | Systematic Assessment | Adeers not subm |
| |
| Sinus bradycardia | Cardiac disorders | Systematic Assessment | Adeers not subm |
| |
| Sinus tachycardia | Cardiac disorders | Systematic Assessment | Adeers not subm |
| |
| Supraventricular tachycardia | Cardiac disorders | Systematic Assessment | Adeers not subm |
| |
| Tricuspid valve disease | Cardiac disorders | Systematic Assessment | Adeers not subm |
| |
| Ventricular arrhythmia | Cardiac disorders | Systematic Assessment | Adeers not subm |
| |
| Ventricular fibrillation | Cardiac disorders | Systematic Assessment | Adeers not subm |
| |
| Ventricular tachycardia | Cardiac disorders | Systematic Assessment | Adeers not subm |
| |
| Congenital, familial and genetic disorders - Other, specify | Congenital, familial and genetic disorders | Systematic Assessment | Adeers not subm |
| |
| Hearing impaired | Ear and labyrinth disorders | Systematic Assessment | Adeers not subm |
| |
| Adrenal insufficiency | Endocrine disorders | Systematic Assessment | Adeers not subm |
| |
| Endocrine disorders - Other, specify | Endocrine disorders | Systematic Assessment | Adeers not subm |
| |
| Blurred vision | Eye disorders | Systematic Assessment | Adeers not subm |
| |
| Eye disorders - Other, specify | Eye disorders | Systematic Assessment | Adeers not subm |
| |
| Eye pain | Eye disorders | Systematic Assessment | Adeers not subm |
| |
| Periorbital edema | Eye disorders | Systematic Assessment | Adeers not subm |
| |
| Vitreous hemorrhage | Eye disorders | Systematic Assessment | Adeers not subm |
| |
| Abdominal distension | Gastrointestinal disorders | Systematic Assessment | Adeers not subm |
| |
| Abdominal pain | Gastrointestinal disorders | Systematic Assessment | Adeers not subm |
| |
| Anal mucositis | Gastrointestinal disorders | Systematic Assessment | Adeers not subm |
| |
| Anal pain | Gastrointestinal disorders | Systematic Assessment | Adeers not subm |
| |
| Anal ulcer | Gastrointestinal disorders | Systematic Assessment | Adeers not subm |
| |
| Ascites | Gastrointestinal disorders | Systematic Assessment | Adeers not subm |
| |
| Colitis | Gastrointestinal disorders | Systematic Assessment | Adeers not subm |
| |
| Constipation | Gastrointestinal disorders | Systematic Assessment | Adeers not subm |
| |
| Dental caries | Gastrointestinal disorders | Systematic Assessment | Adeers not subm |
| |
| Diarrhea | Gastrointestinal disorders | Systematic Assessment | Adeers not subm |
| |
| Duodenal ulcer | Gastrointestinal disorders | Systematic Assessment | Adeers not subm |
| |
| Dysphagia | Gastrointestinal disorders | Systematic Assessment | Adeers not subm |
| |
| Enterocolitis | Gastrointestinal disorders | Systematic Assessment | Adeers not subm |
| |
| Esophageal hemorrhage | Gastrointestinal disorders | Systematic Assessment | Adeers not subm |
| |
| Esophageal pain | Gastrointestinal disorders | Systematic Assessment | Adeers not subm |
| |
| Esophageal ulcer | Gastrointestinal disorders | Systematic Assessment | Adeers not subm |
| |
| Esophagitis | Gastrointestinal disorders | Systematic Assessment | Adeers not subm |
| |
| Gastric hemorrhage | Gastrointestinal disorders | Systematic Assessment | Adeers not subm |
| |
| Gastric ulcer | Gastrointestinal disorders | Systematic Assessment | Adeers not subm |
| |
| Gastritis | Gastrointestinal disorders | Systematic Assessment | Adeers not subm |
| |
| Gastrointestinal disorders - Other, specify | Gastrointestinal disorders | Systematic Assessment | Adeers not subm |
| |
| Gastrointestinal fistula | Gastrointestinal disorders | Systematic Assessment | Adeers not subm |
| |
| Gastrointestinal pain | Gastrointestinal disorders | Systematic Assessment | Adeers not subm |
| |
| Gingival pain | Gastrointestinal disorders | Systematic Assessment | Adeers not subm |
| |
| Ileal perforation | Gastrointestinal disorders | Systematic Assessment | Adeers not subm |
| |
| Ileus | Gastrointestinal disorders | Systematic Assessment | Adeers not subm |
| |
| Lower gastrointestinal hemorrhage | Gastrointestinal disorders | Systematic Assessment | Adeers not subm |
| |
| Malabsorption | Gastrointestinal disorders | Systematic Assessment | Adeers not subm |
| |
| Mucositis oral | Gastrointestinal disorders | Systematic Assessment | Adeers not subm |
| |
| Nausea | Gastrointestinal disorders | Systematic Assessment | Adeers not subm |
| |
| Oral hemorrhage | Gastrointestinal disorders | Systematic Assessment | Adeers not subm |
| |
| Oral pain | Gastrointestinal disorders | Systematic Assessment | Adeers not subm |
| |
| Pancreatitis | Gastrointestinal disorders | Systematic Assessment | Adeers not subm |
| |
| Proctitis | Gastrointestinal disorders | Systematic Assessment | Adeers not subm |
| |
| Rectal mucositis | Gastrointestinal disorders | Systematic Assessment | Adeers not subm |
| |
| Rectal pain | Gastrointestinal disorders | Systematic Assessment | Adeers not subm |
| |
| Retroperitoneal hemorrhage | Gastrointestinal disorders | Systematic Assessment | Adeers not subm |
| |
| Small intestinal mucositis | Gastrointestinal disorders | Systematic Assessment | Adeers not subm |
| |
| Small intestinal obstruction | Gastrointestinal disorders | Systematic Assessment | Adeers not subm |
| |
| Toothache | Gastrointestinal disorders | Systematic Assessment | Adeers not subm |
| |
| Typhlitis | Gastrointestinal disorders | Systematic Assessment | Adeers not subm |
| |
| Upper gastrointestinal hemorrhage | Gastrointestinal disorders | Systematic Assessment | Adeers not subm |
| |
| Vomiting | Gastrointestinal disorders | Systematic Assessment | Adeers not subm |
| |
| Edema face | General disorders | Systematic Assessment | Adeers not subm |
| |
| Edema limbs | General disorders | Systematic Assessment | Adeers not subm |
| |
| Edema trunk | General disorders | Systematic Assessment | Adeers not subm |
| |
| Fatigue | General disorders | Systematic Assessment | Adeers not subm |
| |
| Fever | General disorders | Systematic Assessment | Adeers not subm |
| |
| General disorders and administration site conditions - Other, specify | General disorders | Systematic Assessment | Adeers not subm |
| |
| Localized edema | General disorders | Systematic Assessment | Adeers not subm |
| |
| Multi-organ failure | General disorders | Systematic Assessment | Adeers not subm |
| |
| Non-cardiac chest pain | General disorders | Systematic Assessment | Adeers not subm |
| |
| Pain | General disorders | Systematic Assessment | Adeers not subm |
| |
| Cholecystitis | Hepatobiliary disorders | Systematic Assessment | Adeers not subm |
| |
| Gallbladder necrosis | Hepatobiliary disorders | Systematic Assessment | Adeers not subm |
| |
| Hepatic failure | Hepatobiliary disorders | Systematic Assessment | Adeers not subm |
| |
| Hepatobiliary disorders - Other, specify | Hepatobiliary disorders | Systematic Assessment | Adeers not subm |
| |
| Portal hypertension | Hepatobiliary disorders | Systematic Assessment | Adeers not subm |
| |
| Allergic reaction | Immune system disorders | Systematic Assessment | Adeers not subm |
| |
| Anaphylaxis | Immune system disorders | Systematic Assessment | Adeers not subm |
| |
| Autoimmune disorder | Immune system disorders | Systematic Assessment | Adeers not subm |
| |
| Immune system disorders - Other, specify | Immune system disorders | Systematic Assessment | Adeers not subm |
| |
| Serum sickness | Immune system disorders | Systematic Assessment | Adeers not subm |
| |
| Abdominal infection | Infections and infestations | Systematic Assessment | Adeers not subm |
| |
| Anorectal infection | Infections and infestations | Systematic Assessment | Adeers not subm |
| |
| Appendicitis | Infections and infestations | Systematic Assessment | Adeers not subm |
| |
| Bladder infection | Infections and infestations | Systematic Assessment | Adeers not subm |
| |
| Bone infection | Infections and infestations | Systematic Assessment | Adeers not subm |
| |
| Bronchial infection | Infections and infestations | Systematic Assessment | Adeers not subm |
| |
| Catheter related infection | Infections and infestations | Systematic Assessment | Adeers not subm |
| |
| Cecal infection | Infections and infestations | Systematic Assessment | Adeers not subm |
| |
| Conjunctivitis | Infections and infestations | Systematic Assessment | Adeers not subm |
| |
| Device related infection | Infections and infestations | Systematic Assessment | Adeers not subm |
| |
| Encephalitis infection | Infections and infestations | Systematic Assessment | Adeers not subm |
| |
| Endocarditis infective | Infections and infestations | Systematic Assessment | Adeers not subm |
| |
| Endophthalmitis | Infections and infestations | Systematic Assessment | Adeers not subm |
| |
| Enterocolitis infectious | Infections and infestations | Systematic Assessment | Adeers not subm |
| |
| Esophageal infection | Infections and infestations | Systematic Assessment | Adeers not subm |
| |
| Eye infection | Infections and infestations | Systematic Assessment | Adeers not subm |
| |
| Gallbladder infection | Infections and infestations | Systematic Assessment | Adeers not subm |
| |
| Gum infection | Infections and infestations | Systematic Assessment | Adeers not subm |
| |
| Hepatic infection | Infections and infestations | Systematic Assessment | Adeers not subm |
| |
| Hepatitis viral | Infections and infestations | Systematic Assessment | Adeers not subm |
| |
| Infections and infestations - Other, specify | Infections and infestations | Systematic Assessment | Adeers not subm |
| |
| Infective myositis | Infections and infestations | Systematic Assessment | Adeers not subm |
| |
| Joint infection | Infections and infestations | Systematic Assessment | Adeers not subm |
| |
| Kidney infection | Infections and infestations | Systematic Assessment | Adeers not subm |
| |
| Lip infection | Infections and infestations | Systematic Assessment | Adeers not subm |
| |
| Lung infection | Infections and infestations | Systematic Assessment | Adeers not subm |
| |
| Lymph gland infection | Infections and infestations | Systematic Assessment | Adeers not subm |
| |
| Meningitis | Infections and infestations | Systematic Assessment | Adeers not subm |
| |
| Mucosal infection | Infections and infestations | Systematic Assessment | Adeers not subm |
| |
| Nail infection | Infections and infestations | Systematic Assessment | Adeers not subm |
| |
| Otitis externa | Infections and infestations | Systematic Assessment | Adeers not subm |
| |
| Otitis media | Infections and infestations | Systematic Assessment | Adeers not subm |
| |
| Papulopustular rash | Infections and infestations | Systematic Assessment | Adeers not subm |
| |
| Paronychia | Infections and infestations | Systematic Assessment | Adeers not subm |
| |
| Pelvic infection | Infections and infestations | Systematic Assessment | Adeers not subm |
| |
| Penile infection | Infections and infestations | Systematic Assessment | Adeers not subm |
| |
| Periorbital infection | Infections and infestations | Systematic Assessment | Adeers not subm |
| |
| Peritoneal infection | Infections and infestations | Systematic Assessment | Adeers not subm |
| |
| Pharyngitis | Infections and infestations | Systematic Assessment | Adeers not subm |
| |
| Pleural infection | Infections and infestations | Systematic Assessment | Adeers not subm |
| |
| Salivary gland infection | Infections and infestations | Systematic Assessment | Adeers not subm |
| |
| Scrotal infection | Infections and infestations | Systematic Assessment | Adeers not subm |
| |
| Sepsis | Infections and infestations | Systematic Assessment | Adeers not subm |
| |
| Sinusitis | Infections and infestations | Systematic Assessment | Adeers not subm |
| |
| Skin infection | Infections and infestations | Systematic Assessment | Adeers not subm |
| |
| Small intestine infection | Infections and infestations | Systematic Assessment | Adeers not subm |
| |
| Soft tissue infection | Infections and infestations | Systematic Assessment | Adeers not subm |
| |
| Splenic infection | Infections and infestations | Systematic Assessment | Adeers not subm |
| |
| Tooth infection | Infections and infestations | Systematic Assessment | Adeers not subm |
| |
| Tracheitis | Infections and infestations | Systematic Assessment | Adeers not subm |
| |
| Upper respiratory infection | Infections and infestations | Systematic Assessment | Adeers not subm |
| |
| Urinary tract infection | Infections and infestations | Systematic Assessment | Adeers not subm |
| |
| Vaginal infection | Infections and infestations | Systematic Assessment | Adeers not subm |
| |
| Vulval infection | Infections and infestations | Systematic Assessment | Adeers not subm |
| |
| Wound infection | Infections and infestations | Systematic Assessment | Adeers not subm |
| |
| Infusion related reaction | Injury, poisoning and procedural complications | Systematic Assessment | Adeers not subm |
| |
| Injury, poisoning and procedural complications - Other, specify | Injury, poisoning and procedural complications | Systematic Assessment | Adeers not subm |
| |
| Tracheal obstruction | Injury, poisoning and procedural complications | Systematic Assessment | Adeers not subm |
| |
| Vascular access complication | Injury, poisoning and procedural complications | Systematic Assessment | Adeers not subm |
| |
| Venous injury | Injury, poisoning and procedural complications | Systematic Assessment | Adeers not subm |
| |
| Wound dehiscence | Injury, poisoning and procedural complications | Systematic Assessment | Adeers not subm |
| |
| Activated partial thromboplastin time prolonged | Investigations | Systematic Assessment | Adeers not subm |
| |
| Alanine aminotransferase increased | Investigations | Systematic Assessment | Adeers not subm |
| |
| Alkaline phosphatase increased | Investigations | Systematic Assessment | Adeers not subm |
| |
| Aspartate aminotransferase increased | Investigations | Systematic Assessment | Adeers not subm |
| |
| Blood bilirubin increased | Investigations | Systematic Assessment | Adeers not subm |
| |
| CPK increased | Investigations | Systematic Assessment | Adeers not subm |
| |
| Cardiac troponin I increased | Investigations | Systematic Assessment | Adeers not subm |
| |
| Cholesterol high | Investigations | Systematic Assessment | Adeers not subm |
| |
| Creatinine increased | Investigations | Systematic Assessment | Adeers not subm |
| |
| Ejection fraction decreased | Investigations | Systematic Assessment | Adeers not subm |
| |
| Electrocardiogram QT corrected interval prolonged | Investigations | Systematic Assessment | Adeers not subm |
| |
| Fibrinogen decreased | Investigations | Systematic Assessment | Adeers not subm |
| |
| GGT increased | Investigations | Systematic Assessment | Adeers not subm |
| |
| INR increased | Investigations | Systematic Assessment | Adeers not subm |
| |
| Investigations - Other, specify | Investigations | Systematic Assessment | Adeers not subm |
| |
| Lipase increased | Investigations | Systematic Assessment | Adeers not subm |
| |
| Neutrophil count decreased | Investigations | Systematic Assessment | Adeers not subm |
| |
| Platelet count decreased | Investigations | Systematic Assessment | Adeers not subm |
| |
| Serum amylase increased | Investigations | Systematic Assessment | Adeers not subm |
| |
| Urine output decreased | Investigations | Systematic Assessment | Adeers not subm |
| |
| Weight gain | Investigations | Systematic Assessment | Adeers not subm |
| |
| Weight loss | Investigations | Systematic Assessment | Adeers not subm |
| |
| White blood cell decreased | Investigations | Systematic Assessment | Adeers not subm |
| |
| Acidosis | Metabolism and nutrition disorders | Systematic Assessment | Adeers not subm |
| |
| Alkalosis | Metabolism and nutrition disorders | Systematic Assessment | Adeers not subm |
| |
| Anorexia | Metabolism and nutrition disorders | Systematic Assessment | Adeers not subm |
| |
| Dehydration | Metabolism and nutrition disorders | Systematic Assessment | Adeers not subm |
| |
| Glucose intolerance | Metabolism and nutrition disorders | Systematic Assessment | Adeers not subm |
| |
| Hypercalcemia | Metabolism and nutrition disorders | Systematic Assessment | Adeers not subm |
| |
| Hyperglycemia | Metabolism and nutrition disorders | Systematic Assessment | Adeers not subm |
| |
| Hyperkalemia | Metabolism and nutrition disorders | Systematic Assessment | Adeers not subm |
| |
| Hypermagnesemia | Metabolism and nutrition disorders | Systematic Assessment | Adeers not subm |
| |
| Hypernatremia | Metabolism and nutrition disorders | Systematic Assessment | Adeers not subm |
| |
| Hypertriglyceridemia | Metabolism and nutrition disorders | Systematic Assessment | Adeers not subm |
| |
| Hyperuricemia | Metabolism and nutrition disorders | Systematic Assessment | Adeers not subm |
| |
| Hypoalbuminemia | Metabolism and nutrition disorders | Systematic Assessment | Adeers not subm |
| |
| Hypocalcemia | Metabolism and nutrition disorders | Systematic Assessment | Adeers not subm |
| |
| Hypoglycemia | Metabolism and nutrition disorders | Systematic Assessment | Adeers not subm |
| |
| Hypokalemia | Metabolism and nutrition disorders | Systematic Assessment | Adeers not subm |
| |
| Hypomagnesemia | Metabolism and nutrition disorders | Systematic Assessment | Adeers not subm |
| |
| Hyponatremia | Metabolism and nutrition disorders | Systematic Assessment | Adeers not subm |
| |
| Hypophosphatemia | Metabolism and nutrition disorders | Systematic Assessment | Adeers not subm |
| |
| Iron overload | Metabolism and nutrition disorders | Systematic Assessment | Adeers not subm |
| |
| Metabolism and nutrition disorders - Other, specify | Metabolism and nutrition disorders | Systematic Assessment | Adeers not subm |
| |
| Tumor lysis syndrome | Metabolism and nutrition disorders | Systematic Assessment | Adeers not subm |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | Systematic Assessment | Adeers not subm |
| |
| Avascular necrosis | Musculoskeletal and connective tissue disorders | Systematic Assessment | Adeers not subm |
| |
| Back pain | Musculoskeletal and connective tissue disorders | Systematic Assessment | Adeers not subm |
| |
| Bone pain | Musculoskeletal and connective tissue disorders | Systematic Assessment | Adeers not subm |
| |
| Buttock pain | Musculoskeletal and connective tissue disorders | Systematic Assessment | Adeers not subm |
| |
| Chest wall pain | Musculoskeletal and connective tissue disorders | Systematic Assessment | Adeers not subm |
| |
| Flank pain | Musculoskeletal and connective tissue disorders | Systematic Assessment | Adeers not subm |
| |
| Generalized muscle weakness | Musculoskeletal and connective tissue disorders | Systematic Assessment | Adeers not subm |
| |
| Musculoskeletal and connective tissue disorder - Other, specify | Musculoskeletal and connective tissue disorders | Systematic Assessment | Adeers not subm |
| |
| Myalgia | Musculoskeletal and connective tissue disorders | Systematic Assessment | Adeers not subm |
| |
| Myositis | Musculoskeletal and connective tissue disorders | Systematic Assessment | Adeers not subm |
| |
| Neck pain | Musculoskeletal and connective tissue disorders | Systematic Assessment | Adeers not subm |
| |
| Pain in extremity | Musculoskeletal and connective tissue disorders | Systematic Assessment | Adeers not subm |
| |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | Systematic Assessment | Adeers not subm |
| |
| Aphonia | Nervous system disorders | Systematic Assessment | Adeers not subm |
| |
| Cognitive disturbance | Nervous system disorders | Systematic Assessment | Adeers not subm |
| |
| Depressed level of consciousness | Nervous system disorders | Systematic Assessment | Adeers not subm |
| |
| Dizziness | Nervous system disorders | Systematic Assessment | Adeers not subm |
| |
| Encephalopathy | Nervous system disorders | Systematic Assessment | Adeers not subm |
| |
| Headache | Nervous system disorders | Systematic Assessment | Adeers not subm |
| |
| Hydrocephalus | Nervous system disorders | Systematic Assessment | Adeers not subm |
| |
| Nervous system disorders - Other, specify | Nervous system disorders | Systematic Assessment | Adeers not subm |
| |
| Neuralgia | Nervous system disorders | Systematic Assessment | Adeers not subm |
| |
| Paresthesia | Nervous system disorders | Systematic Assessment | Adeers not subm |
| |
| Peripheral motor neuropathy | Nervous system disorders | Systematic Assessment | Adeers not subm |
| |
| Peripheral sensory neuropathy | Nervous system disorders | Systematic Assessment | Adeers not subm |
| |
| Reversible posterior leukoencephalopathy syndrome | Nervous system disorders | Systematic Assessment | Adeers not subm |
| |
| Seizure | Nervous system disorders | Systematic Assessment | Adeers not subm |
| |
| Stroke | Nervous system disorders | Systematic Assessment | Adeers not subm |
| |
| Syncope | Nervous system disorders | Systematic Assessment | Adeers not subm |
| |
| Vasovagal reaction | Nervous system disorders | Systematic Assessment | Adeers not subm |
| |
| Agitation | Psychiatric disorders | Systematic Assessment | Adeers not subm |
| |
| Anxiety | Psychiatric disorders | Systematic Assessment | Adeers not subm |
| |
| Confusion | Psychiatric disorders | Systematic Assessment | Adeers not subm |
| |
| Delirium | Psychiatric disorders | Systematic Assessment | Adeers not subm |
| |
| Depression | Psychiatric disorders | Systematic Assessment | Adeers not subm |
| |
| Hallucinations | Psychiatric disorders | Systematic Assessment | Adeers not subm |
| |
| Insomnia | Psychiatric disorders | Systematic Assessment | Adeers not subm |
| |
| Irritability | Psychiatric disorders | Systematic Assessment | Adeers not subm |
| |
| Psychiatric disorders - Other, specify | Psychiatric disorders | Systematic Assessment | Adeers not subm |
| |
| Suicidal ideation | Psychiatric disorders | Systematic Assessment | Adeers not subm |
| |
| Acute kidney injury | Renal and urinary disorders | Systematic Assessment | Adeers not subm |
| |
| Cystitis noninfective | Renal and urinary disorders | Systematic Assessment | Adeers not subm |
| |
| Hematuria | Renal and urinary disorders | Systematic Assessment | Adeers not subm |
| |
| Renal and urinary disorders - Other, specify | Renal and urinary disorders | Systematic Assessment | Adeers not subm |
| |
| Renal calculi | Renal and urinary disorders | Systematic Assessment | Adeers not subm |
| |
| Renal colic | Renal and urinary disorders | Systematic Assessment | Adeers not subm |
| |
| Urinary retention | Renal and urinary disorders | Systematic Assessment | Adeers not subm |
| |
| Urinary tract obstruction | Renal and urinary disorders | Systematic Assessment | Adeers not subm |
| |
| Urinary tract pain | Renal and urinary disorders | Systematic Assessment | Adeers not subm |
| |
| Genital edema | Reproductive system and breast disorders | Systematic Assessment | Adeers not subm |
| |
| Menorrhagia | Reproductive system and breast disorders | Systematic Assessment | Adeers not subm |
| |
| Pelvic pain | Reproductive system and breast disorders | Systematic Assessment | Adeers not subm |
| |
| Perineal pain | Reproductive system and breast disorders | Systematic Assessment | Adeers not subm |
| |
| Uterine hemorrhage | Reproductive system and breast disorders | Systematic Assessment | Adeers not subm |
| |
| Vaginal hemorrhage | Reproductive system and breast disorders | Systematic Assessment | Adeers not subm |
| |
| Vaginal inflammation | Reproductive system and breast disorders | Systematic Assessment | Adeers not subm |
| |
| Vaginal pain | Reproductive system and breast disorders | Systematic Assessment | Adeers not subm |
| |
| Adult respiratory distress syndrome | Respiratory, thoracic and mediastinal disorders | Systematic Assessment | Adeers not subm |
| |
| Apnea | Respiratory, thoracic and mediastinal disorders | Systematic Assessment | Adeers not subm |
| |
| Aspiration | Respiratory, thoracic and mediastinal disorders | Systematic Assessment | Adeers not subm |
| |
| Atelectasis | Respiratory, thoracic and mediastinal disorders | Systematic Assessment | Adeers not subm |
| |
| Bronchial obstruction | Respiratory, thoracic and mediastinal disorders | Systematic Assessment | Adeers not subm |
| |
| Bronchopleural fistula | Respiratory, thoracic and mediastinal disorders | Systematic Assessment | Adeers not subm |
| |
| Bronchopulmonary hemorrhage | Respiratory, thoracic and mediastinal disorders | Systematic Assessment | Adeers not subm |
| |
| Dyspnea | Respiratory, thoracic and mediastinal disorders | Systematic Assessment | Adeers not subm |
| |
| Epistaxis | Respiratory, thoracic and mediastinal disorders | Systematic Assessment | Adeers not subm |
| |
| Hoarseness | Respiratory, thoracic and mediastinal disorders | Systematic Assessment | Adeers not subm |
| |
| Hypoxia | Respiratory, thoracic and mediastinal disorders | Systematic Assessment | Adeers not subm |
| |
| Laryngeal edema | Respiratory, thoracic and mediastinal disorders | Systematic Assessment | Adeers not subm |
| |
| Laryngeal mucositis | Respiratory, thoracic and mediastinal disorders | Systematic Assessment | Adeers not subm |
| |
| Laryngeal stenosis | Respiratory, thoracic and mediastinal disorders | Systematic Assessment | Adeers not subm |
| |
| Nasal congestion | Respiratory, thoracic and mediastinal disorders | Systematic Assessment | Adeers not subm |
| |
| Pharyngeal hemorrhage | Respiratory, thoracic and mediastinal disorders | Systematic Assessment | Adeers not subm |
| |
| Pharyngeal mucositis | Respiratory, thoracic and mediastinal disorders | Systematic Assessment | Adeers not subm |
| |
| Pharyngolaryngeal pain | Respiratory, thoracic and mediastinal disorders | Systematic Assessment | Adeers not subm |
| |
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | Systematic Assessment | Adeers not subm |
| |
| Pleural hemorrhage | Respiratory, thoracic and mediastinal disorders | Systematic Assessment | Adeers not subm |
| |
| Pleuritic pain | Respiratory, thoracic and mediastinal disorders | Systematic Assessment | Adeers not subm |
| |
| Pneumonitis | Respiratory, thoracic and mediastinal disorders | Systematic Assessment | Adeers not subm |
| |
| Pneumothorax | Respiratory, thoracic and mediastinal disorders | Systematic Assessment | Adeers not subm |
| |
| Pulmonary edema | Respiratory, thoracic and mediastinal disorders | Systematic Assessment | Adeers not subm |
| |
| Pulmonary hypertension | Respiratory, thoracic and mediastinal disorders | Systematic Assessment | Adeers not subm |
| |
| Respiratory failure | Respiratory, thoracic and mediastinal disorders | Systematic Assessment | Adeers not subm |
| |
| Respiratory, thoracic and mediastinal disorders - Other, specify | Respiratory, thoracic and mediastinal disorders | Systematic Assessment | Adeers not subm |
| |
| Sleep apnea | Respiratory, thoracic and mediastinal disorders | Systematic Assessment | Adeers not subm |
| |
| Sore throat | Respiratory, thoracic and mediastinal disorders | Systematic Assessment | Adeers not subm |
| |
| Stridor | Respiratory, thoracic and mediastinal disorders | Systematic Assessment | Adeers not subm |
| |
| Wheezing | Respiratory, thoracic and mediastinal disorders | Systematic Assessment | Adeers not subm |
| |
| Bullous dermatitis | Skin and subcutaneous tissue disorders | Systematic Assessment | Adeers not subm |
| |
| Erythema multiforme | Skin and subcutaneous tissue disorders | Systematic Assessment | Adeers not subm |
| |
| Erythroderma | Skin and subcutaneous tissue disorders | Systematic Assessment | Adeers not subm |
| |
| Pain of skin | Skin and subcutaneous tissue disorders | Systematic Assessment | Adeers not subm |
| |
| Palmar-plantar erythrodysesthesia syndrome | Skin and subcutaneous tissue disorders | Systematic Assessment | Adeers not subm |
| |
| Pruritus | Skin and subcutaneous tissue disorders | Systematic Assessment | Adeers not subm |
| |
| Rash acneiform | Skin and subcutaneous tissue disorders | Systematic Assessment | Adeers not subm |
| |
| Rash maculo-papular | Skin and subcutaneous tissue disorders | Systematic Assessment | Adeers not subm |
| |
| Skin and subcutaneous tissue disorders - Other, specify | Skin and subcutaneous tissue disorders | Systematic Assessment | Adeers not subm |
| |
| Skin ulceration | Skin and subcutaneous tissue disorders | Systematic Assessment | Adeers not subm |
| |
| Urticaria | Skin and subcutaneous tissue disorders | Systematic Assessment | Adeers not subm |
| |
| Surgical and medical procedures - Other, specify | Surgical and medical procedures | Systematic Assessment | Adeers not subm |
| |
| Capillary leak syndrome | Vascular disorders | Systematic Assessment | Adeers not subm |
| |
| Hematoma | Vascular disorders | Systematic Assessment | Adeers not subm |
| |
| Hypertension | Vascular disorders | Systematic Assessment | Adeers not subm |
| |
| Hypotension | Vascular disorders | Systematic Assessment | Adeers not subm |
| |
| Superficial thrombophlebitis | Vascular disorders | Systematic Assessment | Adeers not subm |
| |
| Thromboembolic event | Vascular disorders | Systematic Assessment | Adeers not subm |
| |
| Vascular disorders - Other, specify | Vascular disorders | Systematic Assessment | Adeers not subm |
|
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Results Reporting Coordinator | Children's Oncology Group | 626-447-0064 | resultsreportingcoordinator@childrensoncologygroup.org |
| Jul 23, 2019 |
| Prot_SAP_000.pdf |
| ID | Term |
|---|---|
| D015470 | Leukemia, Myeloid, Acute |
| D023981 | Sarcoma, Myeloid |
| ID | Term |
|---|---|
| D007951 | Leukemia, Myeloid |
| D007938 | Leukemia |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D012509 | Sarcoma |
| D018204 | Neoplasms, Connective and Soft Tissue |
Not provided
Not provided
| ID | Term |
|---|---|
| D001215 | Asparaginase |
| C001176 | Leyk |
| D000069286 | Bortezomib |
| D003561 | Cytarabine |
| D003630 | Daunorubicin |
| D005047 | Etoposide |
| D008942 | Mitoxantrone |
| D000077157 | Sorafenib |
| ID | Term |
|---|---|
| D000581 | Amidohydrolases |
| D006867 | Hydrolases |
| D004798 | Enzymes |
| D045762 | Enzymes and Coenzymes |
| D001897 | Boronic Acids |
| D000148 | Acids, Noncarboxylic |
| D000143 | Acids |
| D007287 | Inorganic Chemicals |
| D001896 | Boron Compounds |
| D009930 | Organic Chemicals |
| D011719 | Pyrazines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D003562 | Cytidine |
| D011741 | Pyrimidine Nucleosides |
| D011743 | Pyrimidines |
| D001087 | Arabinonucleosides |
| D009705 | Nucleosides |
| D009706 | Nucleic Acids, Nucleotides, and Nucleosides |
| D018943 | Anthracyclines |
| D009279 | Naphthacenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D011083 | Polycyclic Compounds |
| D000617 | Aminoglycosides |
| D006027 | Glycosides |
| D002241 | Carbohydrates |
| D011034 | Podophyllotoxin |
| D013764 | Tetrahydronaphthalenes |
| D009281 | Naphthalenes |
| D005960 | Glucosides |
| D000880 | Anthraquinones |
| D000095322 | Anthrones |
| D000873 | Anthracenes |
| D011809 | Quinones |
| D010671 | Phenylurea Compounds |
| D014508 | Urea |
| D000577 | Amides |
| D001555 | Benzene Derivatives |
| D009536 | Niacinamide |
| D009539 | Nicotinic Acids |
| D000147 | Acids, Heterocyclic |
| D011725 | Pyridines |
Not provided
Not provided
| Male |
|
| Not Hispanic or Latino |
|
| Unknown or Not Reported |
|
| Asian |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
| Canada |
|
| Australia |
|
| New Zealand |
|
| Units | Counts |
|---|
| Participants |
|
|
| Units | Counts |
|---|---|
| Participants |
|
|
| Units | Counts |
|---|
| Participants |
|
|
| OG001 |
| Arm B |
IND I: Pts receive cytarabine IT and ADE chemotherapy as in Induction I, Arm A. Patients also receive bortezomib IV over 3-5 seconds on days 1, 4, 8. IND II: LR pts receive cytarabine IT, ADE chemotherapy, bortezomib as in IND I. HR pts receive cytarabine IT, MA as in IND II, Arm A (HR patients) and bortezomib IV on days 1, 4, 8. INT I: Pts receive cytarabine IT and AE in Arm A, Intensification II, and bortezomib IV on days 1, 4, 8. INT II: LR pts receive cytarabine IT on day 1, MA as in Arm A, IND II (HR patients), and bortezomib IV on days 1, 4, 8. HR pts with no donor for SCT receive high-dose cytarabine IV over 3 hours on days 1, 2, 8, 9 and asparaginase intramuscularly (IM) on days 2 and 9. SCT - Pts receive fludarabine phosphate IV over 30 minutes once daily on days -5 to -2 and busulfan IV over 2 hours 4 times daily on days -5 to -2.Pts undergo allogeneic SCT within 36 to 48 hours after the last dose of busulfan. Pts receive GVHD prophylaxis. |
|
|
| Units |
|---|
| Counts |
|---|
| Participants |
|
|
| Units | Counts |
|---|
| Participants |
|
|
| Units |
|---|
| Counts |
|---|
| Participants |
|
|
| OG001 | Arm B | IND I: Pts receive cytarabine IT and ADE chemotherapy as in Induction I, Arm A. Patients also receive bortezomib IV over 3-5 seconds on days 1, 4, 8. IND II: LR pts receive cytarabine IT, ADE chemotherapy, bortezomib as in IND I. HR pts receive cytarabine IT, MA as in IND II, Arm A (HR patients) and bortezomib IV on days 1, 4, 8. INT I: Pts receive cytarabine IT and AE in Arm A, Intensification II, and bortezomib IV on days 1, 4, 8. INT II: LR pts receive cytarabine IT on day 1, MA as in Arm A, IND II (HR patients), and bortezomib IV on days 1, 4, 8. HR pts with no donor for SCT receive high-dose cytarabine IV over 3 hours on days 1, 2, 8, 9 and asparaginase intramuscularly (IM) on days 2 and 9. SCT - Pts receive fludarabine phosphate IV over 30 minutes once daily on days -5 to -2 and busulfan IV over 2 hours 4 times daily on days -5 to -2.Pts undergo allogeneic SCT within 36 to 48 hours after the last dose of busulfan. Pts receive GVHD prophylaxis. |
|
|
| OG001 | Arm B | IND I: Pts receive cytarabine IT and ADE chemotherapy as in Induction I, Arm A. Patients also receive bortezomib IV over 3-5 seconds on days 1, 4, 8. IND II: LR pts receive cytarabine IT, ADE chemotherapy, bortezomib as in IND I. HR pts receive cytarabine IT, MA as in IND II, Arm A (HR patients) and bortezomib IV on days 1, 4, 8. INT I: Pts receive cytarabine IT and AE in Arm A, Intensification II, and bortezomib IV on days 1, 4, 8. INT II: LR pts receive cytarabine IT on day 1, MA as in Arm A, IND II (HR patients), and bortezomib IV on days 1, 4, 8. HR pts with no donor for SCT receive high-dose cytarabine IV over 3 hours on days 1, 2, 8, 9 and asparaginase intramuscularly (IM) on days 2 and 9. SCT - Pts receive fludarabine phosphate IV over 30 minutes once daily on days -5 to -2 and busulfan IV over 2 hours 4 times daily on days -5 to -2.Pts undergo allogeneic SCT within 36 to 48 hours after the last dose of busulfan. Pts receive GVHD prophylaxis. |
| OG002 | Arm C (Cohort 1) | IND II: Pts receive cytarabine IT on day 1, cytarabine IV over 1-30 minutes on days 1-8, daunorubicin hydrochloride IV over 1-15 minutes on days 1, 3, and 5, etoposide IV over 1-2 hours on days 1-5, sorafenib tosylate PO on days 9-36. INT I: Pts receive cytarabine IT and AE chemotherapy in Arm A, Intensification II, and sorafenib tosylate PO on daily on days 6-28. INT II: Pts receive cytarabine IT on day 1, MA chemotherapy as in Arm A, Induction II (HR patients), sorafenib tosylate PO on days 7-34. SCT (HR patients with matched family [MFD] or unrelated donor): Pts receive fludarabine phosphate IV over 30 minutes once daily on days -5 to -2, busulfan IV over 2 hours 4 times daily on days -5 to -2. Patients undergo allogeneic SCT within 36 to 48 hours after the last dose of busulfan. Pts receive GVHD prophylaxis. MAINTENANCE: Pts receive sorafenib tosylate PO starting day 40-100 after INT II or SCT for one year. |
| OG003 | Arm C (Cohort 2) | IND I: Pts receive cytarabine IT & ADE as in Arm A, IND I & sorafenib tosylate PO at the time of known HR FLT3/ITD+ (including IND I & concurrently with chemo). IND II: Pts receive cytarabine IT day (d) 1, cytarabine IV over 1-30 minutes on d 1-8, daunorubicin hydrochloride IV over 1-15 minutes days 1, 3, 5, etoposide IV over 1-2 hours d 1-5, sorafenib tosylate PO d 9-36. INTE I: Pts receive cytarabine IT and AE in Arm A, INT II, and sorafenib tosylate PO on daily d 6-28. INT II: Pts receive cytarabine IT on d 1, MA as in Arm A, IND II (HR pts), sorafenib tosylate PO d 7-34. SCT (HR patients with matched family [MFD] or unrelated donor): Pts receive fludarabine phosphate IV over 30 minutes once daily on d -5 to -2, busulfan IV over 2 hours 4 times daily d -5 to -2. Pts undergo allogeneic SCT within 36-48 hours after last busulfan dose. Pts receive GVHD prophylaxis. MAINTENANCE: Pts receive sorafenib tosylate PO starting d 40-100 after INT II or SCT for 1 year. |
| OG004 | Arm C (Cohort 3) | IND I: Pts receive cytarabine IT & ADE as in Arm A, IND I & sorafenib tosylate PO days 11-28. IND II: Pts receive cytarabine IT day 1, cytarabine IV over 1-30 minutes on days 1-8, daunorubicin hydrochloride IV over 1-15 minutes days 1, 3, 5, etoposide IV over 1-2 hours days 1-5, sorafenib tosylate PO days 9-36. INT I: Pts receive cytarabine IT & AE as in Arm A, INT II, & sorafenib tosylate PO daily days 6-28. INT II: Pts receive cytarabine IT day 1, MA as in Arm A, IND II (HR patients), & sorafenib tosylate PO days 7-34. SCT (HR patients with matched family [MFD] or unrelated donor): Pts receive fludarabine phosphate IV over 30 minutes once daily on days -5 to -2 and busulfan IV over 2 hours 4 times daily days -5 to -2. Pts undergo allogeneic SCT within 36 to 48 hours after last busulfan dose. Pts receive GVHD prophylaxis. MAINTENANCE: Pts receive sorafenib tosylate PO starting day 40-100 after INT II or SCT for 1 year. |
| OG005 | Arm D | INDUCTION I: Patients with unknown FLT3/ITD status prior to study enrollment receive cytarabine IT and ADE chemotherapy as in Arm A, Induction I. If patients are determined to be HR FLT3/ITD+ no later than the end of Induction I they will be eligible to participate in Arm C. |
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| OG001 | Arm B | IND I: Pts receive cytarabine IT and ADE chemotherapy as in Induction I, Arm A. Patients also receive bortezomib IV over 3-5 seconds on days 1, 4, 8. IND II: LR pts receive cytarabine IT, ADE chemotherapy, bortezomib as in IND I. HR pts receive cytarabine IT, MA as in IND II, Arm A (HR patients) and bortezomib IV on days 1, 4, 8. INT I: Pts receive cytarabine IT and AE in Arm A, Intensification II, and bortezomib IV on days 1, 4, 8. INT II: LR pts receive cytarabine IT on day 1, MA as in Arm A, IND II (HR patients), and bortezomib IV on days 1, 4, 8. HR pts with no donor for SCT receive high-dose cytarabine IV over 3 hours on days 1, 2, 8, 9 and asparaginase intramuscularly (IM) on days 2 and 9. SCT - Pts receive fludarabine phosphate IV over 30 minutes once daily on days -5 to -2 and busulfan IV over 2 hours 4 times daily on days -5 to -2.Pts undergo allogeneic SCT within 36 to 48 hours after the last dose of busulfan. Pts receive GVHD prophylaxis. |
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| OG001 | Arm B | IND I: Pts receive cytarabine IT and ADE chemotherapy as in Induction I, Arm A. Patients also receive bortezomib IV over 3-5 seconds on days 1, 4, 8. IND II: LR pts receive cytarabine IT, ADE chemotherapy, bortezomib as in IND I. HR pts receive cytarabine IT, MA as in IND II, Arm A (HR patients) and bortezomib IV on days 1, 4, 8. INT I: Pts receive cytarabine IT and AE in Arm A, Intensification II, and bortezomib IV on days 1, 4, 8. INT II: LR pts receive cytarabine IT on day 1, MA as in Arm A, IND II (HR patients), and bortezomib IV on days 1, 4, 8. HR pts with no donor for SCT receive high-dose cytarabine IV over 3 hours on days 1, 2, 8, 9 and asparaginase intramuscularly (IM) on days 2 and 9. SCT - Pts receive fludarabine phosphate IV over 30 minutes once daily on days -5 to -2 and busulfan IV over 2 hours 4 times daily on days -5 to -2.Pts undergo allogeneic SCT within 36 to 48 hours after the last dose of busulfan. Pts receive GVHD prophylaxis. |
| OG002 | Arm C (Cohort 1) | IND II: Pts receive cytarabine IT on day 1, cytarabine IV over 1-30 minutes on days 1-8, daunorubicin hydrochloride IV over 1-15 minutes on days 1, 3, and 5, etoposide IV over 1-2 hours on days 1-5, sorafenib tosylate PO on days 9-36. INT I: Pts receive cytarabine IT and AE chemotherapy in Arm A, Intensification II, and sorafenib tosylate PO on daily on days 6-28. INT II: Pts receive cytarabine IT on day 1, MA chemotherapy as in Arm A, Induction II (HR patients), sorafenib tosylate PO on days 7-34. SCT (HR patients with matched family [MFD] or unrelated donor): Pts receive fludarabine phosphate IV over 30 minutes once daily on days -5 to -2, busulfan IV over 2 hours 4 times daily on days -5 to -2. Patients undergo allogeneic SCT within 36 to 48 hours after the last dose of busulfan. Pts receive GVHD prophylaxis. MAINTENANCE: Pts receive sorafenib tosylate PO starting day 40-100 after INT II or SCT for one year. |
| OG003 | Arm C (Cohort 2) | IND I: Pts receive cytarabine IT & ADE as in Arm A, IND I & sorafenib tosylate PO at the time of known HR FLT3/ITD+ (including IND I & concurrently with chemo). IND II: Pts receive cytarabine IT day (d) 1, cytarabine IV over 1-30 minutes on d 1-8, daunorubicin hydrochloride IV over 1-15 minutes days 1, 3, 5, etoposide IV over 1-2 hours d 1-5, sorafenib tosylate PO d 9-36. INTE I: Pts receive cytarabine IT and AE in Arm A, INT II, and sorafenib tosylate PO on daily d 6-28. INT II: Pts receive cytarabine IT on d 1, MA as in Arm A, IND II (HR pts), sorafenib tosylate PO d 7-34. SCT (HR patients with matched family [MFD] or unrelated donor): Pts receive fludarabine phosphate IV over 30 minutes once daily on d -5 to -2, busulfan IV over 2 hours 4 times daily d -5 to -2. Pts undergo allogeneic SCT within 36-48 hours after last busulfan dose. Pts receive GVHD prophylaxis. MAINTENANCE: Pts receive sorafenib tosylate PO starting d 40-100 after INT II or SCT for 1 year. |
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| OG001 | Arm B | IND I: Pts receive cytarabine IT and ADE chemotherapy as in Induction I, Arm A. Patients also receive bortezomib IV over 3-5 seconds on days 1, 4, 8. IND II: LR pts receive cytarabine IT, ADE chemotherapy, bortezomib as in IND I. HR pts receive cytarabine IT, MA as in IND II, Arm A (HR patients) and bortezomib IV on days 1, 4, 8. INT I: Pts receive cytarabine IT and AE in Arm A, Intensification II, and bortezomib IV on days 1, 4, 8. INT II: LR pts receive cytarabine IT on day 1, MA as in Arm A, IND II (HR patients), and bortezomib IV on days 1, 4, 8. HR pts with no donor for SCT receive high-dose cytarabine IV over 3 hours on days 1, 2, 8, 9 and asparaginase intramuscularly (IM) on days 2 and 9. SCT - Pts receive fludarabine phosphate IV over 30 minutes once daily on days -5 to -2 and busulfan IV over 2 hours 4 times daily on days -5 to -2.Pts undergo allogeneic SCT within 36 to 48 hours after the last dose of busulfan. Pts receive GVHD prophylaxis. |
| OG002 | Arm C (Cohort 1) | IND II: Pts receive cytarabine IT on day 1, cytarabine IV over 1-30 minutes on days 1-8, daunorubicin hydrochloride IV over 1-15 minutes on days 1, 3, and 5, etoposide IV over 1-2 hours on days 1-5, sorafenib tosylate PO on days 9-36. INT I: Pts receive cytarabine IT and AE chemotherapy in Arm A, Intensification II, and sorafenib tosylate PO on daily on days 6-28. INT II: Pts receive cytarabine IT on day 1, MA chemotherapy as in Arm A, Induction II (HR patients), sorafenib tosylate PO on days 7-34. SCT (HR patients with matched family [MFD] or unrelated donor): Pts receive fludarabine phosphate IV over 30 minutes once daily on days -5 to -2, busulfan IV over 2 hours 4 times daily on days -5 to -2. Patients undergo allogeneic SCT within 36 to 48 hours after the last dose of busulfan. Pts receive GVHD prophylaxis. MAINTENANCE: Pts receive sorafenib tosylate PO starting day 40-100 after INT II or SCT for one year. |
| OG003 | Arm C (Cohort 2) | IND I: Pts receive cytarabine IT & ADE as in Arm A, IND I & sorafenib tosylate PO at the time of known HR FLT3/ITD+ (including IND I & concurrently with chemo). IND II: Pts receive cytarabine IT day (d) 1, cytarabine IV over 1-30 minutes on d 1-8, daunorubicin hydrochloride IV over 1-15 minutes days 1, 3, 5, etoposide IV over 1-2 hours d 1-5, sorafenib tosylate PO d 9-36. INTE I: Pts receive cytarabine IT and AE in Arm A, INT II, and sorafenib tosylate PO on daily d 6-28. INT II: Pts receive cytarabine IT on d 1, MA as in Arm A, IND II (HR pts), sorafenib tosylate PO d 7-34. SCT (HR patients with matched family [MFD] or unrelated donor): Pts receive fludarabine phosphate IV over 30 minutes once daily on d -5 to -2, busulfan IV over 2 hours 4 times daily d -5 to -2. Pts undergo allogeneic SCT within 36-48 hours after last busulfan dose. Pts receive GVHD prophylaxis. MAINTENANCE: Pts receive sorafenib tosylate PO starting d 40-100 after INT II or SCT for 1 year. |
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| OG001 | Arm B | IND I: Pts receive cytarabine IT and ADE chemotherapy as in Induction I, Arm A. Patients also receive bortezomib IV over 3-5 seconds on days 1, 4, 8. IND II: LR pts receive cytarabine IT, ADE chemotherapy, bortezomib as in IND I. HR pts receive cytarabine IT, MA as in IND II, Arm A (HR patients) and bortezomib IV on days 1, 4, 8. INT I: Pts receive cytarabine IT and AE in Arm A, Intensification II, and bortezomib IV on days 1, 4, 8. INT II: LR pts receive cytarabine IT on day 1, MA as in Arm A, IND II (HR patients), and bortezomib IV on days 1, 4, 8. HR pts with no donor for SCT receive high-dose cytarabine IV over 3 hours on days 1, 2, 8, 9 and asparaginase intramuscularly (IM) on days 2 and 9. SCT - Pts receive fludarabine phosphate IV over 30 minutes once daily on days -5 to -2 and busulfan IV over 2 hours 4 times daily on days -5 to -2.Pts undergo allogeneic SCT within 36 to 48 hours after the last dose of busulfan. Pts receive GVHD prophylaxis. |
| OG002 | Arm C (Cohort 1) | IND II: Pts receive cytarabine IT on day 1, cytarabine IV over 1-30 minutes on days 1-8, daunorubicin hydrochloride IV over 1-15 minutes on days 1, 3, and 5, etoposide IV over 1-2 hours on days 1-5, sorafenib tosylate PO on days 9-36. INT I: Pts receive cytarabine IT and AE chemotherapy in Arm A, Intensification II, and sorafenib tosylate PO on daily on days 6-28. INT II: Pts receive cytarabine IT on day 1, MA chemotherapy as in Arm A, Induction II (HR patients), sorafenib tosylate PO on days 7-34. SCT (HR patients with matched family [MFD] or unrelated donor): Pts receive fludarabine phosphate IV over 30 minutes once daily on days -5 to -2, busulfan IV over 2 hours 4 times daily on days -5 to -2. Patients undergo allogeneic SCT within 36 to 48 hours after the last dose of busulfan. Pts receive GVHD prophylaxis. MAINTENANCE: Pts receive sorafenib tosylate PO starting day 40-100 after INT II or SCT for one year. |
| OG003 | Arm C (Cohort 2) | IND I: Pts receive cytarabine IT & ADE as in Arm A, IND I & sorafenib tosylate PO at the time of known HR FLT3/ITD+ (including IND I & concurrently with chemo). IND II: Pts receive cytarabine IT day (d) 1, cytarabine IV over 1-30 minutes on d 1-8, daunorubicin hydrochloride IV over 1-15 minutes days 1, 3, 5, etoposide IV over 1-2 hours d 1-5, sorafenib tosylate PO d 9-36. INTE I: Pts receive cytarabine IT and AE in Arm A, INT II, and sorafenib tosylate PO on daily d 6-28. INT II: Pts receive cytarabine IT on d 1, MA as in Arm A, IND II (HR pts), sorafenib tosylate PO d 7-34. SCT (HR patients with matched family [MFD] or unrelated donor): Pts receive fludarabine phosphate IV over 30 minutes once daily on d -5 to -2, busulfan IV over 2 hours 4 times daily d -5 to -2. Pts undergo allogeneic SCT within 36-48 hours after last busulfan dose. Pts receive GVHD prophylaxis. MAINTENANCE: Pts receive sorafenib tosylate PO starting d 40-100 after INT II or SCT for 1 year. |
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| Arm B |
IND I: Pts receive cytarabine IT and ADE chemotherapy as in Induction I, Arm A. Patients also receive bortezomib IV over 3-5 seconds on days 1, 4, 8. IND II: LR pts receive cytarabine IT, ADE chemotherapy, bortezomib as in IND I. HR pts receive cytarabine IT, MA as in IND II, Arm A (HR patients) and bortezomib IV on days 1, 4, 8. INT I: Pts receive cytarabine IT and AE in Arm A, Intensification II, and bortezomib IV on days 1, 4, 8. INT II: LR pts receive cytarabine IT on day 1, MA as in Arm A, IND II (HR patients), and bortezomib IV on days 1, 4, 8. HR pts with no donor for SCT receive high-dose cytarabine IV over 3 hours on days 1, 2, 8, 9 and asparaginase intramuscularly (IM) on days 2 and 9. SCT - Pts receive fludarabine phosphate IV over 30 minutes once daily on days -5 to -2 and busulfan IV over 2 hours 4 times daily on days -5 to -2.Pts undergo allogeneic SCT within 36 to 48 hours after the last dose of busulfan. Pts receive GVHD prophylaxis. |
| OG002 | Arm C (Cohort 1) | IND II: Pts receive cytarabine IT on day 1, cytarabine IV over 1-30 minutes on days 1-8, daunorubicin hydrochloride IV over 1-15 minutes on days 1, 3, and 5, etoposide IV over 1-2 hours on days 1-5, sorafenib tosylate PO on days 9-36. INT I: Pts receive cytarabine IT and AE chemotherapy in Arm A, Intensification II, and sorafenib tosylate PO on daily on days 6-28. INT II: Pts receive cytarabine IT on day 1, MA chemotherapy as in Arm A, Induction II (HR patients), sorafenib tosylate PO on days 7-34. SCT (HR patients with matched family [MFD] or unrelated donor): Pts receive fludarabine phosphate IV over 30 minutes once daily on days -5 to -2, busulfan IV over 2 hours 4 times daily on days -5 to -2. Patients undergo allogeneic SCT within 36 to 48 hours after the last dose of busulfan. Pts receive GVHD prophylaxis. MAINTENANCE: Pts receive sorafenib tosylate PO starting day 40-100 after INT II or SCT for one year. |
| OG003 | Arm C (Cohort 2) | IND I: Pts receive cytarabine IT & ADE as in Arm A, IND I & sorafenib tosylate PO at the time of known HR FLT3/ITD+ (including IND I & concurrently with chemo). IND II: Pts receive cytarabine IT day (d) 1, cytarabine IV over 1-30 minutes on d 1-8, daunorubicin hydrochloride IV over 1-15 minutes days 1, 3, 5, etoposide IV over 1-2 hours d 1-5, sorafenib tosylate PO d 9-36. INTE I: Pts receive cytarabine IT and AE in Arm A, INT II, and sorafenib tosylate PO on daily d 6-28. INT II: Pts receive cytarabine IT on d 1, MA as in Arm A, IND II (HR pts), sorafenib tosylate PO d 7-34. SCT (HR patients with matched family [MFD] or unrelated donor): Pts receive fludarabine phosphate IV over 30 minutes once daily on d -5 to -2, busulfan IV over 2 hours 4 times daily d -5 to -2. Pts undergo allogeneic SCT within 36-48 hours after last busulfan dose. Pts receive GVHD prophylaxis. MAINTENANCE: Pts receive sorafenib tosylate PO starting d 40-100 after INT II or SCT for 1 year. |
| OG004 | Arm C (Cohort 3) | IND I: Pts receive cytarabine IT & ADE as in Arm A, IND I & sorafenib tosylate PO days 11-28. IND II: Pts receive cytarabine IT day 1, cytarabine IV over 1-30 minutes on days 1-8, daunorubicin hydrochloride IV over 1-15 minutes days 1, 3, 5, etoposide IV over 1-2 hours days 1-5, sorafenib tosylate PO days 9-36. INT I: Pts receive cytarabine IT & AE as in Arm A, INT II, & sorafenib tosylate PO daily days 6-28. INT II: Pts receive cytarabine IT day 1, MA as in Arm A, IND II (HR patients), & sorafenib tosylate PO days 7-34. SCT (HR patients with matched family [MFD] or unrelated donor): Pts receive fludarabine phosphate IV over 30 minutes once daily on days -5 to -2 and busulfan IV over 2 hours 4 times daily days -5 to -2. Pts undergo allogeneic SCT within 36 to 48 hours after last busulfan dose. Pts receive GVHD prophylaxis. MAINTENANCE: Pts receive sorafenib tosylate PO starting day 40-100 after INT II or SCT for 1 year. |
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| Arm B |
IND I: Pts receive cytarabine IT and ADE chemotherapy as in Induction I, Arm A. Patients also receive bortezomib IV over 3-5 seconds on days 1, 4, 8. IND II: LR pts receive cytarabine IT, ADE chemotherapy, bortezomib as in IND I. HR pts receive cytarabine IT, MA as in IND II, Arm A (HR patients) and bortezomib IV on days 1, 4, 8. INT I: Pts receive cytarabine IT and AE in Arm A, Intensification II, and bortezomib IV on days 1, 4, 8. INT II: LR pts receive cytarabine IT on day 1, MA as in Arm A, IND II (HR patients), and bortezomib IV on days 1, 4, 8. HR pts with no donor for SCT receive high-dose cytarabine IV over 3 hours on days 1, 2, 8, 9 and asparaginase intramuscularly (IM) on days 2 and 9. SCT - Pts receive fludarabine phosphate IV over 30 minutes once daily on days -5 to -2 and busulfan IV over 2 hours 4 times daily on days -5 to -2.Pts undergo allogeneic SCT within 36 to 48 hours after the last dose of busulfan. Pts receive GVHD prophylaxis. |
| OG002 | Arm C (Cohort 1) | IND II: Pts receive cytarabine IT on day 1, cytarabine IV over 1-30 minutes on days 1-8, daunorubicin hydrochloride IV over 1-15 minutes on days 1, 3, and 5, etoposide IV over 1-2 hours on days 1-5, sorafenib tosylate PO on days 9-36. INT I: Pts receive cytarabine IT and AE chemotherapy in Arm A, Intensification II, and sorafenib tosylate PO on daily on days 6-28. INT II: Pts receive cytarabine IT on day 1, MA chemotherapy as in Arm A, Induction II (HR patients), sorafenib tosylate PO on days 7-34. SCT (HR patients with matched family [MFD] or unrelated donor): Pts receive fludarabine phosphate IV over 30 minutes once daily on days -5 to -2, busulfan IV over 2 hours 4 times daily on days -5 to -2. Patients undergo allogeneic SCT within 36 to 48 hours after the last dose of busulfan. Pts receive GVHD prophylaxis. MAINTENANCE: Pts receive sorafenib tosylate PO starting day 40-100 after INT II or SCT for one year. |
| OG003 | Arm C (Cohort 2) | IND I: Pts receive cytarabine IT & ADE as in Arm A, IND I & sorafenib tosylate PO at the time of known HR FLT3/ITD+ (including IND I & concurrently with chemo). IND II: Pts receive cytarabine IT day (d) 1, cytarabine IV over 1-30 minutes on d 1-8, daunorubicin hydrochloride IV over 1-15 minutes days 1, 3, 5, etoposide IV over 1-2 hours d 1-5, sorafenib tosylate PO d 9-36. INTE I: Pts receive cytarabine IT and AE in Arm A, INT II, and sorafenib tosylate PO on daily d 6-28. INT II: Pts receive cytarabine IT on d 1, MA as in Arm A, IND II (HR pts), sorafenib tosylate PO d 7-34. SCT (HR patients with matched family [MFD] or unrelated donor): Pts receive fludarabine phosphate IV over 30 minutes once daily on d -5 to -2, busulfan IV over 2 hours 4 times daily d -5 to -2. Pts undergo allogeneic SCT within 36-48 hours after last busulfan dose. Pts receive GVHD prophylaxis. MAINTENANCE: Pts receive sorafenib tosylate PO starting d 40-100 after INT II or SCT for 1 year. |
| OG004 | Arm C (Cohort 3) | IND I: Pts receive cytarabine IT & ADE as in Arm A, IND I & sorafenib tosylate PO days 11-28. IND II: Pts receive cytarabine IT day 1, cytarabine IV over 1-30 minutes on days 1-8, daunorubicin hydrochloride IV over 1-15 minutes days 1, 3, 5, etoposide IV over 1-2 hours days 1-5, sorafenib tosylate PO days 9-36. INT I: Pts receive cytarabine IT & AE as in Arm A, INT II, & sorafenib tosylate PO daily days 6-28. INT II: Pts receive cytarabine IT day 1, MA as in Arm A, IND II (HR patients), & sorafenib tosylate PO days 7-34. SCT (HR patients with matched family [MFD] or unrelated donor): Pts receive fludarabine phosphate IV over 30 minutes once daily on days -5 to -2 and busulfan IV over 2 hours 4 times daily days -5 to -2. Pts undergo allogeneic SCT within 36 to 48 hours after last busulfan dose. Pts receive GVHD prophylaxis. MAINTENANCE: Pts receive sorafenib tosylate PO starting day 40-100 after INT II or SCT for 1 year. |
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| OG002 | Arm C (Cohort 1) | IND II: Pts receive cytarabine IT on day 1, cytarabine IV over 1-30 minutes on days 1-8, daunorubicin hydrochloride IV over 1-15 minutes on days 1, 3, and 5, etoposide IV over 1-2 hours on days 1-5, sorafenib tosylate PO on days 9-36. INT I: Pts receive cytarabine IT and AE chemotherapy in Arm A, Intensification II, and sorafenib tosylate PO on daily on days 6-28. INT II: Pts receive cytarabine IT on day 1, MA chemotherapy as in Arm A, Induction II (HR patients), sorafenib tosylate PO on days 7-34. SCT (HR patients with matched family [MFD] or unrelated donor): Pts receive fludarabine phosphate IV over 30 minutes once daily on days -5 to -2, busulfan IV over 2 hours 4 times daily on days -5 to -2. Patients undergo allogeneic SCT within 36 to 48 hours after the last dose of busulfan. Pts receive GVHD prophylaxis. MAINTENANCE: Pts receive sorafenib tosylate PO starting day 40-100 after INT II or SCT for one year. |
| OG003 | Arm C (Cohort 2) | IND I: Pts receive cytarabine IT & ADE as in Arm A, IND I & sorafenib tosylate PO at the time of known HR FLT3/ITD+ (including IND I & concurrently with chemo). IND II: Pts receive cytarabine IT day (d) 1, cytarabine IV over 1-30 minutes on d 1-8, daunorubicin hydrochloride IV over 1-15 minutes days 1, 3, 5, etoposide IV over 1-2 hours d 1-5, sorafenib tosylate PO d 9-36. INTE I: Pts receive cytarabine IT and AE in Arm A, INT II, and sorafenib tosylate PO on daily d 6-28. INT II: Pts receive cytarabine IT on d 1, MA as in Arm A, IND II (HR pts), sorafenib tosylate PO d 7-34. SCT (HR patients with matched family [MFD] or unrelated donor): Pts receive fludarabine phosphate IV over 30 minutes once daily on d -5 to -2, busulfan IV over 2 hours 4 times daily d -5 to -2. Pts undergo allogeneic SCT within 36-48 hours after last busulfan dose. Pts receive GVHD prophylaxis. MAINTENANCE: Pts receive sorafenib tosylate PO starting d 40-100 after INT II or SCT for 1 year. |
| OG004 | Arm C (Cohort 3) | IND I: Pts receive cytarabine IT & ADE as in Arm A, IND I & sorafenib tosylate PO days 11-28. IND II: Pts receive cytarabine IT day 1, cytarabine IV over 1-30 minutes on days 1-8, daunorubicin hydrochloride IV over 1-15 minutes days 1, 3, 5, etoposide IV over 1-2 hours days 1-5, sorafenib tosylate PO days 9-36. INT I: Pts receive cytarabine IT & AE as in Arm A, INT II, & sorafenib tosylate PO daily days 6-28. INT II: Pts receive cytarabine IT day 1, MA as in Arm A, IND II (HR patients), & sorafenib tosylate PO days 7-34. SCT (HR patients with matched family [MFD] or unrelated donor): Pts receive fludarabine phosphate IV over 30 minutes once daily on days -5 to -2 and busulfan IV over 2 hours 4 times daily days -5 to -2. Pts undergo allogeneic SCT within 36 to 48 hours after last busulfan dose. Pts receive GVHD prophylaxis. MAINTENANCE: Pts receive sorafenib tosylate PO starting day 40-100 after INT II or SCT for 1 year. |
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