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| Name | Class |
|---|---|
| Ambit Biosciences Corporation | INDUSTRY |
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This is a phase I study of the investigational drug AC220 combined with cytarabine and etoposide in pediatric patients with relapsed acute lymphoblastic leukemia (ALL) and acute myelogenous leukemia (AML).
This is a study for pediatric patients with relapsed acute lymphoblastic leukemia (ALL) or acute myelogenous leukemia (AML). Some people diagnosed with leukemia have changes in a receptor located on the surface of white blood cells called FLT3. This is known as a FLT3 mutation. FLT3 plays an important role in the way cells grow and divide. In normal cells, the FLT3 receptor is switched off most of the time and only switches on when it gets a chemical signal from outside. But cells with the FLT3 mutation have the grow signal permanently switched on. This means leukemia cells with the FLT3 mutation are growing and dividing all the time. Doctors have found that people with leukemia cells that carry FLT3 mutations are less likely to go into remission with chemotherapy and have a higher risk of the leukemia coming back after treatment.
This is a study of an investigational drug called AC220. AC220 is considered investigational because it has not been approved in the United States by the Food and Drug Administration (FDA). AC220 is a drug which is able to "turn off" the FLT3 grow signal. AC220 will be given with cytarabine and etoposide to treat the relapsed leukemia. This is a phase I study, which means that the study is being done to find the highest dose of AC220 that can be given safely with the drugs cytarabine and etoposide to children and young adults.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| ALL AC220 @ 25mg/m2/day (Dose Level 1) | Experimental | The starting dose is Dose Level 1 at 25 mg/m2/day. Dose escalation will proceed from level 1 to 2 to 3, and so on, assuming the maximum tolerated dose is not exceeded. Patients will received etoposide and cytarabine on Days 1-5, and AC220 on Day 7 through 28. IT Methotrexate will be given to patients with ALL on Day 0, dose assigned by age. |
|
| AML AC220 @ 25mg/m2/day (Dose Level 1) | Experimental | The starting dose is Dose Level 1 at 25 mg/m2/day. Dose escalation will proceed from level 1 to 2 to 3, and so on, assuming the maximum tolerated dose is not exceeded. Patients will received etoposide and cytarabine on Days 1-5, and AC220 on Day 7 through 28. IT cytarabine will be given to patients with AML on Day 0, dose assigned by age. |
|
| ALL AC220 @ 40mg/m2/day (Dose Level 2) | Experimental | Dose escalation will proceed from level 1 to level 2 for AC220 at 40mg/m2/day, assuming the maximum tolerated dose is not exceeded. Patients will received etoposide and cytarabine on Days 1-5, and AC220 on Day 7 through 28. IT Methotrexate will be given to patients with ALL on Day 0, dose assigned by age. |
|
| ALL AC220 @ 60mg/m2/day (Dose Level 3) | Experimental |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| AC220 | Drug | Dose assigned at study entry. AC220 will be given orally once daily on days 7-28. |
|
| Measure | Description | Time Frame |
|---|---|---|
| The Dose of AC220 That is Safe and Biologically Active When Given in Sequential Combination With Ara-C/Etoposide | The incidence of dose limiting toxicity (DLT) will be measured. The maximum tolerated dose will be the highest study dose at which 1 or fewer of six patients experience DLT during cycle 1 of therapy. Plasma inhibitor activity (PIA) will be measured Pre-treatment and on Days 7, 14, 21 and 28 of Course 1. For the MTD to be considered biologically active, we will require that 7 of 9 patients achieve PIA of > 90% at 3 of 4 trough time points. | 4 weeks from therapy start |
| Measure | Description | Time Frame |
|---|---|---|
| Disease Response | Possible outcomes are: Complete Remission (CR), Complete Remission without Platelet Recovery (CRp), complete response with incomplete hematologic recovery (CRi), Stable Disease, Progressive Disease, Induction Death, or Relapse | 10 weeks |
| Count of Participants According to Inhibition of FLT3 Phosphorylation |
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Inclusion Criteria:
Patients must be greater than 1 month and ≤ 21 years of age at study entry.
Patients must have a diagnosis of relapsed/refractory AML, ALL or acute leukemia of ambiguous lineage and meet the following criteria:
Karnofsky > 50% for patients >16 years of age and Lansky >50% for patients ≤16 years of age.
Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study.
Myelosuppressive chemotherapy:
Hematopoietic growth factors: At least 7 days since the completion of therapy with a growth factor.
Biologic (anti-neoplastic agent): At least 7 days since the completion of therapy with a biologic agent. For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur. The duration of this interval must be discussed with the study chair.
XRT: 2 wks must have elapsed since local palliative XRT for CNS chloromas; No washout period is necessary for other chloromas; at least 3 months must have elapsed if prior TBI, craniospinal XRT.
Hematopoetic Stem Cell Transplant: At least 90 days must have elapsed since hematopoietic stem cell transplant (HSCT) and patients must not have active GVHD.
Patient must have adequate renal and hepatic functions as indicated by the following laboratory values:
Patient must have a shortening fraction of ≥ 27% by echocardiogram, OR an ejection fraction of ≥ 50% by radionuclide angiogram.
Reproductive Function
Exclusion Criteria:
Patients will be excluded if they have CNS 3 disease.
Patients will be excluded if they have uncontrolled or significant cardiovascular disease, including:
Patients will be excluded if they have a systemic fungal, bacterial, viral or other infection that is exhibiting ongoing signs/symptoms related to the infection without improvement despite appropriate antibiotics or other treatment. The patient needs to be off pressors and have negative blood cultures for 48 hours.
Patient is receiving or plans to receive concomitant chemotherapy, radiation therapy, or immunotherapy other than as specified in the protocol.
Any significant concurrent disease, illness, psychiatric disorder or social issue that would compromise patient safety or compliance, interfere with consent, study participation, follow up, or interpretation of study results.
Patients who are concurrently receiving CYP3A4 and 5 inhibitors and inducers
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| Name | Affiliation | Role |
|---|---|---|
| Todd Cooper, MD | Children's Healthcare of Atlanta, Emory University | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Childrens Hospital Los Angeles | Los Angeles | California | 90027 | United States | ||
| Children's Hospital Central California |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 26920889 | Result | Cooper TM, Cassar J, Eckroth E, Malvar J, Sposto R, Gaynon P, Chang BH, Gore L, August K, Pollard JA, DuBois SG, Silverman LB, Oesterheld J, Gammon G, Magoon D, Annesley C, Brown PA. A Phase I Study of Quizartinib Combined with Chemotherapy in Relapsed Childhood Leukemia: A Therapeutic Advances in Childhood Leukemia & Lymphoma (TACL) Study. Clin Cancer Res. 2016 Aug 15;22(16):4014-22. doi: 10.1158/1078-0432.CCR-15-1998. Epub 2016 Feb 26. |
| Label | URL |
|---|---|
| Therapeutic Advances in Childhood Leukemia \& Lymphoma Consortium web site | View source |
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| ID | Title | Description |
|---|---|---|
| FG000 | ALL AC220 @ 25mg/m^2/Day (Dose Level 1) | The starting dose is Dose Level 1 at 25 mg/m^2/day. Dose escalation will proceed from level 1 to 2 to 3, and so on, assuming the maximum tolerated dose is not exceeded. Patients will received etoposide and cytarabine on Days 1-5, and AC220 on Day 7 through 28. IT Methotrexate will be given to patients with ALL on Day 0, dose assigned by age. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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Dose escalation will proceed from level 2 to 3 for AC220 at 60mg/m2/day, assuming the maximum tolerated dose is not exceeded. Patients will received etoposide and cytarabine on Days 1-5, and AC220 on Day 7 through 28. IT Methotrexate will be given to patients with ALL on Day 0, dose assigned by age. If toxicity at Dose Level 3 would allow further escalation, but demonstrated sufficient AC220 activity, no further dose escalation will be required.
|
| ALL AC220 @ 90mg/m2/day (Dose Level 4) | Experimental | If the study dose of 60 mg/m2/day at Dose Level 3 is well tolerated but does not show sufficient AC220 activity, the study may proceed to Dose Level 4 at 90 mg/m2/day. Patients will received etoposide and cytarabine on Days 1-5, and AC220 on Day 7 through 28. IT Methotrexate will be given to patients with ALL on Day 0, dose assigned by age. If toxicity at Dose Level 4 would allow further escalation, but demonstrated sufficient AC220 activity, no further dose escalation will be required. |
|
| ALL AC220 @ 130 mg/m2/day (Dose Level 5) | Experimental | If the study dose of 90 mg/m2/day at Dose Level 4 is well tolerated but does not show sufficient AC220 activity, the study may proceed to Dose Level 5 at 130 mg/m2/day. Patients will received etoposide and cytarabine on Days 1-5, and AC220 on Day 7 through 28. IT Methotrexate will be given to patients with ALL on Day 0, dose assigned by age. Dose Level 5 is the highest dose for this study. |
|
| AML AC220 @ 40mg/m2/day (Dose Level 2) | Experimental | Dose escalation will proceed from level 1 to level 2 for AC220 at 40mg/m2/day, assuming the maximum tolerated dose is not exceeded. Patients will received etoposide and cytarabine on Days 1-5, and AC220 on Day 7 through 28. IT cytarabine will be given to patients with AML on Day 0, dose assigned by age. |
|
| AML AC220 @ 60mg/m2/day (Dose Level 3) | Experimental | Dose escalation will proceed from level 2 to 3 for AC220 at 60mg/m2/day, assuming the maximum tolerated dose is not exceeded. Patients will received etoposide and cytarabine on Days 1-5, and AC220 on Day 7 through 28. IT cytarabine will be given to patients with AML on Day 0, dose assigned by age. If toxicity at Dose Level 3 would allow further escalation, but demonstrated sufficient AC220 activity, no further dose escalation will be required. |
|
| AML AC220 @ 90mg/m2/day (Dose Level 4) | Experimental | If the study dose of 60 mg/m2/day at Dose Level 3 is well tolerated but does not show sufficient AC220 activity, the study may proceed to Dose Level 4 at 90 mg/m2/day. Patients will received etoposide and cytarabine on Days 1-5, and AC220 on Day 7 through 28. IT cytarabine will be given to patients with AML on Day 0, dose assigned by age. If toxicity at Dose Level 4 would allow further escalation, but demonstrated sufficient AC220 activity, no further dose escalation will be required. |
|
| AML AC220 @ 130mg/m2/day (Dose Level 5) | Experimental | If the study dose of 90 mg/m2/day at Dose Level 4 is well tolerated but does not show sufficient AC220 activity, the study may proceed to Dose Level 5 at 130 mg/m2/day. Patients will received etoposide and cytarabine on Days 1-5, and AC220 on Day 7 through 28. IT cytarabine will be given to patients with AML on Day 0, dose assigned by age. Dose Level 5 is the highest dose for this study. |
|
|
| Cytarabine | Drug | All patients receive 1000 mg/m2/day IV given every 12 hours on days 1 through 5. Additionally, AML patients and patients with ambiguous leukemia receive cytarabine intrathecally on day "1" of course 1 and 2. Dose defined by age:
|
|
|
| Etoposide | Drug | 150 mg/m2/day IV on days 1 through 5. |
|
|
| Methotrexate | Drug | IT methotrexate given intrathecally to patients with ALL on day "0" of course 1 and 2. Dose defined by age
|
|
|
PIA samples will be collected pre-treatment and on Days 7, 14, 21 and 28 of Course 1. |
| 4 weeks from therapy start |
| Madera |
| California |
| 93636 |
| United States |
| UCSF School of Medicine | San Francisco | California | 94143-0106 | United States |
| The Children's Hospital, University of Colorado | Aurora | Colorado | 80045 | United States |
| Children's Healthcare of Atlanta, Emory University | Atlanta | Georgia | 30322 | United States |
| Johns Hopkins University | Baltimore | Maryland | 21231 | United States |
| Dana Farber | Boston | Massachusetts | 02215 | United States |
| Children's Mercy Hospitals and Clinics | Kansas City | Missouri | 64108 | United States |
| Levine Children's Hospital at Carolinas Medical Center | Charlotte | North Carolina | 28203 | United States |
| Oregon Health and Science University | Portland | Oregon | 97239 | United States |
| Seattle Children's Hospital | Seattle | Washington | 98105 | United States |
| FG001 | AML AC220 @ 25mg/m^2/Day (Dose Level 1) | The starting dose is Dose Level 1 at 25 mg/m^2/day. Dose escalation will proceed from level 1 to 2 to 3, and so on, assuming the maximum tolerated dose is not exceeded. Patients will received etoposide and cytarabine on Days 1-5, and AC220 on Day 7 through 28. IT cytarabine will be given to patients with AML on Day 0, dose assigned by age. |
| FG002 | ALL AC220 @ 40mg/m^2/Day (Dose Level 2) | Dose escalation will proceed from level 1 to level 2 for AC220 at 40mg/m^2/day, assuming the maximum tolerated dose is not exceeded. Patients will received etoposide and cytarabine on Days 1-5, and AC220 on Day 7 through 28. IT Methotrexate will be given to patients with ALL on Day 0, dose assigned by age. |
| FG003 | AML AC220 @ 40mg/m^2/Day (Dose Level 2) | Dose escalation will proceed from level 1 to level 2 for AC220 at 40mg/m^2/day, assuming the maximum tolerated dose is not exceeded. Patients will received etoposide and cytarabine on Days 1-5, and AC220 on Day 7 through 28. IT cytarabine will be given to patients with AML on Day 0, dose assigned by age. |
| FG004 | ALL AC220 @ 60mg/m^2/Day (Dose Level 3) | Dose escalation will proceed from level 2 to 3 for AC220 at 60mg/m^2/day, assuming the maximum tolerated dose is not exceeded. Patients will received etoposide and cytarabine on Days 1-5, and AC220 on Day 7 through 28. IT Methotrexate will be given to patients with ALL on Day 0, dose assigned by age. If toxicity at Dose Level 3 would allow further escalation, but demonstrated sufficient AC220 activity, no further dose escalation will be required. |
| FG005 | AML AC220 @ 60mg/m^2/Day (Dose Level 3) | Dose escalation will proceed from level 2 to 3 for AC220 at 60mg/m^2/day, assuming the maximum tolerated dose is not exceeded. Patients will received etoposide and cytarabine on Days 1-5, and AC220 on Day 7 through 28. IT cytarabine will be given to patients with AML on Day 0, dose assigned by age. If toxicity at Dose Level 3 would allow further escalation, but demonstrated sufficient AC220 activity, no further dose escalation will be required. |
| FG006 | ALL AC220 @ 90mg/m^2/Day (Dose Level 4) | If the study dose of 60 mg/m^2/day at Dose Level 3 is well tolerated but does not show sufficient AC220 activity, the study may proceed to Dose Level 4 at 90 mg/m2/day. Patients will received etoposide and cytarabine on Days 1-5, and AC220 on Day 7 through 28. IT Methotrexate will be given to patients with ALL on Day 0, dose assigned by age. If toxicity at Dose Level 4 would allow further escalation, but demonstrated sufficient AC220 activity, no further dose escalation will be required. |
| FG007 | AML AC220 @ 90mg/m^2/Day (Dose Level 4) | If the study dose of 60 mg/m^2/day at Dose Level 3 is well tolerated but does not show sufficient AC220 activity, the study may proceed to Dose Level 4 at 90 mg/m^2/day. Patients will received etoposide and cytarabine on Days 1-5, and AC220 on Day 7 through 28. IT cytarabine will be given to patients with AML on Day 0, dose assigned by age. If toxicity at Dose Level 4 would allow further escalation, but demonstrated sufficient AC220 activity, no further dose escalation will be required. |
| FG008 | ALL AC220 @ 130mg/m^2/Day (Dose Level 5) | If the study dose of 90 mg/m^2/day at Dose Level 4 is well tolerated but does not show sufficient AC220 activity, the study may proceed to Dose Level 5 at 130 mg/m^2/day. Patients will received etoposide and cytarabine on Days 1-5, and AC220 on Day 7 through 28. IT Methotrexate will be given to patients with ALL on Day 0, dose assigned by age. Dose Level 5 is the highest dose for this study. |
| FG009 | AML AC220 @ 130mg/m^2/Day (Dose Level 5) | If the study dose of 90 mg/m^2/day at Dose Level 4 is well tolerated but does not show sufficient AC220 activity, the study may proceed to Dose Level 5 at 130 mg/m^2/day. Patients will received etoposide and cytarabine on Days 1-5, and AC220 on Day 7 through 28. IT cytarabine will be given to patients with AML on Day 0, dose assigned by age. Dose Level 5 is the highest dose for this study. |
| COMPLETED |
|
| NOT COMPLETED |
|
No patients with ALL were enrolled into Dose Level 1
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| ID | Title | Description |
|---|---|---|
| BG000 | ALL AC220 @ 25mg/m2/Day (Dose Level 1) | The starting dose is Dose Level 1 at 25 mg/m^2/day. Dose escalation will proceed from level 1 to 2 to 3, and so on, assuming the maximum tolerated dose is not exceeded. Patients will received etoposide and cytarabine on Days 1-5, and AC220 on Day 7 through 28. IT Methotrexate will be given to patients with ALL on Day 0, dose assigned by age. |
| BG001 | AML AC220 @ 25mg/m2/Day (Dose Level 1) | The starting dose is Dose Level 1 at 25 mg/m^2/day. Dose escalation will proceed from level 1 to 2 to 3, and so on, assuming the maximum tolerated dose is not exceeded. Patients will received etoposide and cytarabine on Days 1-5, and AC220 on Day 7 through 28. IT cytarabine will be given to patients with AML on Day 0, dose assigned by age. |
| BG002 | ALL AC220 @ 40mg/m2/Day (Dose Level 2) | Dose escalation will proceed from level 1 to level 2 for AC220 at 40mg/m^2/day, assuming the maximum tolerated dose is not exceeded. Patients will received etoposide and cytarabine on Days 1-5, and AC220 on Day 7 through 28. IT Methotrexate will be given to patients with ALL on Day 0, dose assigned by age. |
| BG003 | AML AC220 @ 40mg/m2/Day (Dose Level 2) | Dose escalation will proceed from level 1 to level 2 for AC220 at 40mg/m^2/day, assuming the maximum tolerated dose is not exceeded. Patients will received etoposide and cytarabine on Days 1-5, and AC220 on Day 7 through 28. IT Cytarabine will be given to patients with AML on Day 0, dose assigned by age. |
| BG004 | ALL AC220 @ 60mg/m2/Day (Dose Level 3) | Dose escalation will proceed from level 2 to 3 for AC220 at 60mg/m^2/day, assuming the maximum tolerated dose is not exceeded. Patients will received etoposide and cytarabine on Days 1-5, and AC220 on Day 7 through 28. IT Methotrexate will be given to patients with ALL on Day 0, dose assigned by age. If toxicity at Dose Level 3 would allow further escalation, but demonstrated sufficient AC220 activity, no further dose escalation will be required. |
| BG005 | AML AC220 @ 60mg/m2/Day (Dose Level 3) | Dose escalation will proceed from level 2 to 3 for AC220 at 60mg/m^2/day, assuming the maximum tolerated dose is not exceeded. Patients will received etoposide and cytarabine on Days 1-5, and AC220 on Day 7 through 28. IT cytarabine will be given to patients with AML on Day 0, dose assigned by age. If toxicity at Dose Level 3 would allow further escalation, but demonstrated sufficient AC220 activity, no further dose escalation will be required. |
| 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 | Median | Full Range | years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| Race (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| # Patients with Prior HSCT | Count of Participants | Participants |
| ||||||||||||||||
| FLT3/ITD+ (FLT3-internal tandem duplication mutation) | Count of Participants | 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 | The Dose of AC220 That is Safe and Biologically Active When Given in Sequential Combination With Ara-C/Etoposide | The incidence of dose limiting toxicity (DLT) will be measured. The maximum tolerated dose will be the highest study dose at which 1 or fewer of six patients experience DLT during cycle 1 of therapy. Plasma inhibitor activity (PIA) will be measured Pre-treatment and on Days 7, 14, 21 and 28 of Course 1. For the MTD to be considered biologically active, we will require that 7 of 9 patients achieve PIA of > 90% at 3 of 4 trough time points. | No patients with ALL were enrolled during Dose Level 1. | Posted | Count of Participants | Participants | 4 weeks from therapy start |
|
|
| |||||||||||||||||||||||||||||||||||||||||
| Secondary | Disease Response | Possible outcomes are: Complete Remission (CR), Complete Remission without Platelet Recovery (CRp), complete response with incomplete hematologic recovery (CRi), Stable Disease, Progressive Disease, Induction Death, or Relapse | Five of 22 patients were not evaluable for response per protocol because they were removed from protocol therapy prior to disease assessment without meeting PD criteria | Posted | Count of Participants | Participants | 10 weeks |
|
| ||||||||||||||||||||||||||||||||||||||||||
| Secondary | Count of Participants According to Inhibition of FLT3 Phosphorylation | PIA samples will be collected pre-treatment and on Days 7, 14, 21 and 28 of Course 1. | Nineteen of 22 patients had PIA assessment. | Posted | Count of Participants | Participants | 4 weeks from therapy start |
|
|
Adverse events and suspected adverse reactions will be collected and reported on the electronic CRFs beginning with the first dose of study therapy until 30 days following the last dose of study therapy (a period of approximately 90 days).
The definitions of AE and SAE do not differ from the clinicaltrials.gov definitions.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | ALL Dose Level 1 | The starting dose is Dose Level 1 at 25 mg/m^2/day. Dose escalation will proceed from level 1 to 2 to 3, and so on, assuming the maximum tolerated dose is not exceeded. Patients will received etoposide and cytarabine on Days 1-5, and AC220 on Day 7 through 28. IT Methotrexate will be given to patients with ALL on Day 0, dose assigned by age. | 0 | 0 | 0 | 0 | 0 | 0 |
| EG001 | AML Dose Level 1 | The starting dose is Dose Level 1 at 25 mg/m^2/day. Dose escalation will proceed from level 1 to 2 to 3, and so on, assuming the maximum tolerated dose is not exceeded. Patients will received etoposide and cytarabine on Days 1-5, and AC220 on Day 7 through 28. IT cytarabine will be given to patients with AML on Day 0, dose assigned by age. | 2 | 3 | 2 | 3 | 3 | 3 |
| EG002 | ALL Dose Level 2 | Dose escalation will proceed from level 1 to level 2 for AC220 at 40mg/m^2/day, assuming the maximum tolerated dose is not exceeded. Patients will received etoposide and cytarabine on Days 1-5, and AC220 on Day 7 through 28. IT Methotrexate will be given to patients with ALL on Day 0, dose assigned by age. | 2 | 2 | 1 | 2 | 2 | 2 |
| EG003 | AML Dose Level 2 | Dose escalation will proceed from level 1 to level 2 for AC220 at 40mg/m^2/day, assuming the maximum tolerated dose is not exceeded. Patients will received etoposide and cytarabine on Days 1-5, and AC220 on Day 7 through 28. IT Cytarabine will be given to patients with AML on Day 0, dose assigned by age. | 3 | 5 | 3 | 5 | 5 | 5 |
| EG004 | ALL Dose Level 3 | Dose escalation will proceed from level 2 to 3 for AC220 at 60mg/m^2/day, assuming the maximum tolerated dose is not exceeded. Patients will received etoposide and cytarabine on Days 1-5, and AC220 on Day 7 through 28. IT Methotrexate will be given to patients with ALL on Day 0, dose assigned by age. If toxicity at Dose Level 3 would allow further escalation, but demonstrated sufficient AC220 activity, no further dose escalation will be required. | 1 | 2 | 0 | 2 | 2 | 2 |
| EG005 | AML Dose Level 3 | Dose escalation will proceed from level 2 to 3 for AC220 at 60mg/m^2/day, assuming the maximum tolerated dose is not exceeded. Patients will received etoposide and cytarabine on Days 1-5, and AC220 on Day 7 through 28. IT Cytarabine will be given to patients with AML on Day 0, dose assigned by age. If toxicity at Dose Level 3 would allow further escalation, but demonstrated sufficient AC220 activity, no further dose escalation will be required. | 3 | 10 | 4 | 10 | 10 | 10 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaphylaxis | Immune system disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Blood bilirubin increased | Investigations | CTCAE (4.0) | Systematic Assessment |
| |
| Chest wall pain | General disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Febrile neutropenia | Blood and lymphatic system disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Fever | General disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Hypokalemia | Metabolism and nutrition disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Hypotension | Vascular disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Infections and infestations - Other, Not Specified | Infections and infestations | CTCAE (4.0) | Systematic Assessment | Blood infections of non-specified lineage |
|
| Lipase increased | Investigations | CTCAE (4.0) | Systematic Assessment |
| |
| Lung infection | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
| |
| Pancreatitis | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Pulmonary edema | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Respiratory failure | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Sepsis | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
| |
| Skin & subcutaneous tissue disorder-Other | Skin and subcutaneous tissue disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Skin infection | Skin and subcutaneous tissue disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Infection and Infestations - Rhinovirus | Blood and lymphatic system disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Infections and Infestations - Staphylococcus epidermidis | Blood and lymphatic system disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Infections and Infestations - streptococcal pharyngitis | Blood and lymphatic system disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Infections and Infestations - Pseudomonas | Blood and lymphatic system disorders | CTCAE (4.0) | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Activated partial thromboplastin time prolonged | Investigations | CTCAE (4.0) | Systematic Assessment |
| |
| Alanine aminotransferase increased | Investigations | CTCAE (4.0) | Systematic Assessment |
| |
| Alkaline phosphatase increased | Investigations | CTCAE (4.0) | Systematic Assessment |
| |
| Anemia | Blood and lymphatic system disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Anorexia | Metabolism and nutrition disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Aspartate aminotransferase increased | Investigations | CTCAE (4.0) | Systematic Assessment |
| |
| Blood bilirubin increased | Investigations | CTCAE (4.0) | Systematic Assessment |
| |
| Catheter related infection | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Creatinine increased | Investigations | CTCAE (4.0) | Systematic Assessment |
| |
| Diarrhea | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Dyspnea | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Febrile neutropenia | Blood and lymphatic system disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Fever | General disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Hyperglycemia | Metabolism and nutrition disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Hypermagnesemia | Metabolism and nutrition disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Hypertension | Vascular disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Hypoalbuminemia | Metabolism and nutrition disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Hypocalcemia | Metabolism and nutrition disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Hypokalemia | Metabolism and nutrition disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Hypomagnesemia | Metabolism and nutrition disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Hyponatremia | Metabolism and nutrition disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Hypophosphatemia | Metabolism and nutrition disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Hypotension | Vascular disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Hypoxia | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Infections and infestations - Other - Not otherwise Specified | Infections and infestations | CTCAE (4.0) | Systematic Assessment | The lineage of the infection was not recorded nor specified |
|
| Lung infection | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
| |
| Lymphocyte count decreased | Blood and lymphatic system disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Mucositis oral | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Neutrophil count decreased | Blood and lymphatic system disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Pain | General disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Pain in extremity | Musculoskeletal and connective tissue disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Platelet count decreased | Blood and lymphatic system disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Rash maculo-papular | Skin and subcutaneous tissue disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Rectal pain | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Skin & subcutaneous tissue disorder-Other - Not otherwise specified | Skin and subcutaneous tissue disorders | CTCAE (4.0) | Systematic Assessment | The lineage of these skin and subcutaneous tissue disorders were not specified |
|
| Sore throat | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
| |
| White blood cell decreased | Investigations | CTCAE (4.0) | Systematic Assessment |
| |
| Device related infection | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
| |
| Pancreatitis | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Perirectal Abcess | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
| |
| Pilonidal cyst | Skin and subcutaneous tissue disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Blood Culture infection | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
| |
| Headache | General disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Tachypnea | General disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Rhinorrhea | General disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Erythmea | Skin and subcutaneous tissue disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Irritation to central line site | General disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Left neck peeling | Skin and subcutaneous tissue disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Drainage & reddened skin at Hickman CL site | Skin and subcutaneous tissue disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Ara-C Skin Rash | Skin and subcutaneous tissue disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Skin Nodules - Not otherwise specified | Skin and subcutaneous tissue disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Strep Veridans Bacteremia | Blood and lymphatic system disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Rash on Chest and Upper Arms | Skin and subcutaneous tissue disorders | CTCAE (4.0) | Systematic Assessment |
|
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Peggy Romano, BA, CCRP | Therapeutic Advances in Childhood Leukemia & Lymphoma (TACL) / Children's Hospital Los Angeles | 323-361-5505 | promano@chla.usc.edu |
| ID | Term |
|---|---|
| D054198 | Precursor Cell Lymphoblastic Leukemia-Lymphoma |
| D007951 | Leukemia, Myeloid |
| D012008 | Recurrence |
| D007938 | Leukemia |
| ID | Term |
|---|---|
| D007945 | Leukemia, Lymphoid |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D008232 | Lymphoproliferative Disorders |
| D008206 | Lymphatic Diseases |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
Not provided
Not provided
| ID | Term |
|---|---|
| C544967 | quizartinib |
| D003561 | Cytarabine |
| D005047 | Etoposide |
| C061400 | etoposide phosphate |
| D008727 | Methotrexate |
| ID | Term |
|---|---|
| D003562 | Cytidine |
| D011741 | Pyrimidine Nucleosides |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D001087 | Arabinonucleosides |
| D009705 | Nucleosides |
| D009706 | Nucleic Acids, Nucleotides, and Nucleosides |
| D011034 | Podophyllotoxin |
| D013764 | Tetrahydronaphthalenes |
| D009281 | Naphthalenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D011083 | Polycyclic Compounds |
| D005960 | Glucosides |
| D006027 | Glycosides |
| D002241 | Carbohydrates |
| D000630 | Aminopterin |
| D011622 | Pterins |
| D011621 | Pteridines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
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 |
|
| patients experienced DLT |
|
| patients withdrew or not evaluable |
|
| Participants |
|
|
| Title | Denominators | Categories |
|---|
|