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| ID | Type | Description | Link |
|---|---|---|---|
| NCI-2009-00318 | Registry Identifier | CTRP (Clinical Trial Reporting Program) | |
| CDR0000492776 | Other Identifier | Clinical Trials.gov | |
| COG-AAML0431 | Other Identifier | Children's Oncology Group | |
| AAML0431 | Other Identifier | CTEP | |
| U10CA098543 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Cancer Institute (NCI) | NIH |
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This phase III trial is studying how well combination chemotherapy works in treating young patients with Down syndrome and acute myeloid leukemia or myelodysplastic syndromes. 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 more than one drug (combination chemotherapy) may kill more cancer cells.
PRIMARY OBJECTIVES:
I. Determine the event-free survival (EFS) and overall survival rates in pediatric patients with Down syndrome (DS) and acute myeloid leukemia AML or myelodysplastic syndromes MDS treated with induction therapy comprising cytarabine, daunorubicin hydrochloride, thioguanine, and asparaginase followed by intensification therapy comprising cytarabine and etoposide.
II. Determine if the EFS rate in these patients can be increased with an intensified course of cytarabine therapy during induction therapy, compared to the EFS rate of patients in protocol COG-A2971.
III. Determine if the number of intrathecal chemotherapy treatments can be reduced in these patients.
IV. Determine if the total cumulative anthracycline dose can be reduced in these patients.
SECONDARY OBJECTIVES:
I. Determine the type and degree of treatment-related toxicity in these patients.
II. Determine the prevalence of leukemia phenotype and globin transcription factor 1 (GATA1) mutations of DS patients < 4 years of age at diagnosis.
III. Determine the relationship of GATA1 mutations with leukemia phenotype and EFS rates of DS patients < 4 years of age at diagnosis.
IV. Determine the relationship of minimal residual disease monitored by flow cytometry and remission status during and after completion of therapy based on bone marrow morphology.
V. Examine parameters of in vitro drug sensitivity and in vivo Ara-C pharmacokinetics.
VI. Examine gene expression profiles by microarrays and the relationship to leukemia phenotype and outcome.
VII. Examine the relationship of functional polymorphisms in phase I and phase II detoxification genes and DNA repair pathways that may modify susceptibility to leukemia and outcome of therapy in DS children.
VIII. Assess the effect of karyotypic abnormalities on survival. IX. Establish a DS leukemia cell bank for future biological studies.
OUTLINE: This is a nonrandomized, multicenter study.
INDUCTION THERAPY: Patients undergo 4 courses of induction therapy. Each course is 28 days.
COURSE I: Patients receive intrathecal (IT) cytarabine on day 1* and cytarabine IV continuously over 96 hours, daunorubicin hydrochloride IV continuously over 96 hours, and oral thioguanine twice daily on days 1-4.
NOTE: *Patients with Central Nervous System (CNS) disease receive cytarabine IT twice weekly for up to 6 doses; patients with persistent CNS leukemia after 6 doses of IT cytarabine are removed from the study.
COURSE II: Patients receive high-dose cytarabine IV over 3 hours twice daily on days 1, 2, 8, and 9 and asparaginase intramuscularly (IM) on days 2 and 9.
COURSE III: Patients receive treatment as in course 1.
COURSE IV: Patients receive cytarabine IV, daunorubicin hydrochloride IV, and oral thioguanine as in course 1.
Induction therapy continues in the absence of disease progression or unacceptable toxicity. Patients with partial response, relapsed, or refractory disease after completion of course 4 are taken off study. Patients achieving complete response proceed to intensification therapy.
INTENSIFICATION THERAPY: Patients receive cytarabine IV continuously over 168 hours on days 1-7 and etoposide IV over 1 hour on days 1-3. Treatment repeats every 28 days for 2 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up periodically for 5 years and then annually thereafter.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Treatment (combination chemotherapy) | Experimental | INDUCTION THERAPY COURSE I: Patients receive cytarabine IT on day 1 and cytarabine IV continuously over 96 hours, daunorubicin hydrochloride IV continuously, and oral thioguanine BID on days 1-4. COURSE II: Patients receive high-dose cytarabine IV over 3 hours BID on days 1, 2, 8, and 9 and asparaginase (IM) on days 2 and 9. COURSE III: Patients receive treatment as in course I. COURSE IV: Patients receive cytarabine IV, daunorubicin hydrochloride IV, and oral thioguanine as in course I INTENSIFICATION THERAPY: Patients receive cytarabine IV continuously over 168 hours on days 1-7 and etoposide IV over 1 hour on days 1-3. Treatment repeats every 28 days for 2 courses in the absence of disease progression or unacceptable toxicity. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| asparaginase | Drug | Given IM |
|
|
| Measure | Description | Time Frame |
|---|---|---|
| Event-free Survival (EFS) at 3 Years | Time from study entry to induction failure, relapse, or death assessed at 3 years. | |
| Overall Survival (OS) at 3 Years | Time from study entry to death, assessed at 3 years. |
| Measure | Description | Time Frame |
|---|---|---|
| Induction Remission Rate | Proportion of participants with a remission after four courses of Induction therapy. | End of induction therapy (day 112) |
| Percentage of Patients Experiencing Grade 3 or 4 Toxicity Assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 |
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Inclusion Criteria:
Diagnosis DS or DS mosaicism by karyotype or chromosomal analysis
Diagnosis of myelodysplastic syndromes (MDS) with < 30% blasts or acute myeloid leukemia (AML)
Patients with a history of transient myeloproliferative disorder (TMD) are eligible provided the patient is diagnosed with AML or MDS at > 90 days of age AND meets either of the following criteria:
Immunophenotype required for study entry
No promyelocytic leukemia
Shortening fraction ≥ 27% by echocardiogram OR ejection fraction ≥ 50% by radionuclide angiogram
Bilirubin ≤ 1.5 times upper limit of normal (ULN)
AST or ALT < 2.5 times ULN
Creatinine adjusted according to age as follows:
Creatinine clearance or radioisotope glomerular filtration rate at least 70 mL/min
No evidence of dyspnea at rest
No exercise intolerance
Pulse oximetry > 94%
No prior chemotherapy, radiotherapy, or any antileukemic therapy
Prior therapy for TMD allowed
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| Name | Affiliation | Role |
|---|---|---|
| Jeffrey Taub, MD | Children's Oncology Group | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Phoenix Childrens Hospital | Phoenix | Arizona | 85016 | United States | ||
| Southern California Permanente Medical Group |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 28389462 | Derived | Taub JW, Berman JN, Hitzler JK, Sorrell AD, Lacayo NJ, Mast K, Head D, Raimondi S, Hirsch B, Ge Y, Gerbing RB, Wang YC, Alonzo TA, Campana D, Coustan-Smith E, Mathew P, Gamis AS. Improved outcomes for myeloid leukemia of Down syndrome: a report from the Children's Oncology Group AAML0431 trial. Blood. 2017 Jun 22;129(25):3304-3313. doi: 10.1182/blood-2017-01-764324. Epub 2017 Apr 7. |
| 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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| ID | Title | Description |
|---|---|---|
| FG000 | Treatment (Combination Chemotherapy) | INDUCTION THERAPY COURSE I: Patients receive cytarabine IT on day 1 and cytarabine IV continuously over 96 hours, daunorubicin hydrochloride IV continuously, and oral thioguanine BID on days 1-4. COURSE II: Patients receive high-dose cytarabine IV over 3 hours BID on days 1, 2, 8, and 9 and asparaginase (IM) on days 2 and 9. COURSE III: Patients receive treatment as in course I. COURSE IV: Patients receive cytarabine IV, daunorubicin hydrochloride IV, and oral thioguanine as in course I INTENSIFICATION THERAPY: Patients receive cytarabine IV continuously over 168 hours on days 1-7 and etoposide IV over 1 hour on days 1-3. Treatment repeats every 28 days for 2 courses in the absence of disease progression or unacceptable toxicity. asparaginase: Given IM daunorubicin hydrochloride: Given IV cytarabine: Given IV or IT thioguanine: Given orally etoposide: Given IV laboratory biomarker analysis: Correlative studies |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| daunorubicin hydrochloride | Drug | Given IV |
|
|
| cytarabine | Drug | Given IV or IT |
|
|
| thioguanine | Drug | Given orally |
|
|
| etoposide | Drug | Given IV |
|
|
| laboratory biomarker analysis | Other | Correlative studies |
|
Proportion of participants with at least one grade 3 or higher adverse event during therapy. |
| From the beginning of induction therapy to the end of intensification therapy |
| Prevalence of Leukemia Phenotype of DS Patients < 4 Years of Age at Diagnosis by Flow Cytometry | Proportion of participants having megakaryoblastic subtype (AMkL) phenotype among patients with phenotype data available. | At the start of therapy |
| Prevalence of of GATA1 Mutations of DS Patients < 4 Years of Age at Diagnosis | Proportion of participants having GATA1 mutation among patients with phenotype data available. | At baseline and at the end of therapy (intensification) or disease relapse |
| Proportions of Patients in Morphologic Remission With Positive MRD by Flow Cytometry | Proportion of participants in complete remission by morphology and with positive MRD by flow cytometry among patients having evaluable remission and MRD assessment. | After Induction I therapy (day 28 from start of therapy) |
| Cytarabine Drug Sensitivity by R-Strip (MicroMath) Curve Fitting Program | Mean and standard deviation of peak plasma concentration. Specimen draws were performed only with dose 1, day 1 of induction II of AraC. First sample drawn pre-infusion, then drawn 30 mins prior to the end of the infusion, and then drawn for 6 time periods post infusion up to 8 hours post infusion (and before the 2nd dose of AraC). Results are based from these multiple time points on Day 1 of Induction II only. | Days 1, 2, 8, and 9 of induction II |
| Cytarabine Drug Sensitivity by R-Strip (MicroMath) Curve Fitting Program | Mean and standard deviation of area under the concentration time curve. Specimen draws were performed only with dose 1, day 1 of induction II of AraC. First sample drawn pre-infusion, then drawn 30 mins prior to the end of the infusion, and then drawn for 6 time periods post infusion up to 8 hours post infusion (and before the 2nd dose of AraC). Results are based from these multiple time points on Day 1 of Induction II only. | Days 1, 2, 8, and 9 of induction II |
| Cytarabine Drug Sensitivity by R-Strip (MicroMath) Curve Fitting Program | Mean and standard deviation of half-life of elimination. Specimen draws were performed only with dose 1, day 1 of induction II of AraC. First sample drawn pre-infusion, then drawn 30 mins prior to the end of the infusion, and then drawn for 6 time periods post infusion up to 8 hours post infusion (and before the 2nd dose of AraC). Results are based from these multiple time points on Day 1 of Induction II only. | Days 1, 2, 8, and 9 of induction II |
| Gene Expression Profiles by Microarrays | A hierarchical clustering algorithm is used to assemble the genes into a dendrogram or tree structure with branches containing genes with similar patterns of expression. This ordered representation can be graphically displayed with colors that reflect the qualitative and quantitative relationships of the expressed genes. | At baseline and at the time of relapse (if available) |
| Downey |
| California |
| 90242 |
| United States |
| Miller Children's Hospital | Long Beach | California | 90806 | United States |
| Children's Hospital Los Angeles | Los Angeles | California | 90027 | United States |
| Children's Hospital Central California | Madera | California | 93636-8762 | United States |
| Children's Hospital and Research Center at Oakland | Oakland | California | 94609-1809 | United States |
| Kaiser Permanente-Oakland | Oakland | California | 94611 | United States |
| Childrens Hospital of Orange County | Orange | California | 92868-3874 | United States |
| Lucile Packard Children's Hospital Stanford University | Palo Alto | California | 94304 | United States |
| Rady Children's Hospital - San Diego | San Diego | California | 92123 | United States |
| University of California San Francisco Medical Center-Parnassus | San Francisco | California | 94143 | United States |
| Children's Hospital Colorado | Aurora | Colorado | 80045 | United States |
| Alfred I duPont Hospital for Children | Wilmington | Delaware | 19803 | United States |
| Children's National Medical Center | Washington D.C. | District of Columbia | 20010 | United States |
| Lombardi Comprehensive Cancer Center at Georgetown University | Washington D.C. | District of Columbia | 20057 | United States |
| Broward Health Medical Center | Fort Lauderdale | Florida | 33316 | United States |
| Memorial Healthcare System - Joe DiMaggio Children's Hospital | Hollywood | Florida | 33021 | United States |
| Nemours Children's Clinic - Jacksonville | Jacksonville | Florida | 32207-8426 | United States |
| Florida Hospital | Orlando | Florida | 32803 | United States |
| All Children's Hospital | St. Petersburg | Florida | 33701 | United States |
| Children's Healthcare of Atlanta - Egleston | Atlanta | Georgia | 30322 | United States |
| University of Hawaii | Honolulu | Hawaii | 96813 | United States |
| Saint Luke's Mountain States Tumor Institute | Boise | Idaho | 83712 | United States |
| Lurie Children's Hospital-Chicago | Chicago | Illinois | 60614 | United States |
| Loyola University Medical Center | Maywood | Illinois | 60153 | United States |
| Advocate Lutheran General Hospital. | Park Ridge | Illinois | 60068 | United States |
| Saint Jude Midwest Affiliate | Peoria | Illinois | 61602 | United States |
| Southern Illinois University | Springfield | Illinois | 62702 | United States |
| Indiana University Medical Center | Indianapolis | Indiana | 46202 | United States |
| Riley Hospital for Children | Indianapolis | Indiana | 46202 | United States |
| Saint Vincent Hospital and Health Services | Indianapolis | Indiana | 46260 | United States |
| Kosair Children's Hospital | Louisville | Kentucky | 40202 | United States |
| Tulane University Health Sciences Center | New Orleans | Louisiana | 70112 | United States |
| Eastern Maine Medical Center | Bangor | Maine | 04401 | 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 |
| C S Mott Children's Hospital | Ann Arbor | Michigan | 48109 | United States |
| Wayne State University-Karmanos Cancer Institute | Detroit | Michigan | 48201 | United States |
| Saint John Hospital and Medical Center | Detroit | Michigan | 48236 | United States |
| Hurley Medical Center | Flint | Michigan | 48502 | United States |
| Helen DeVos Children's Hospital at Spectrum Health | Grand Rapids | Michigan | 49503 | United States |
| Children's Hospitals and Clinics of Minnesota - Minneapolis | Minneapolis | Minnesota | 55404 | United States |
| University of Minnesota Medical Center-Fairview | Minneapolis | Minnesota | 55455 | United States |
| University of Mississippi Medical Center | Jackson | Mississippi | 39216 | United States |
| The Childrens Mercy Hospital | Kansas City | Missouri | 64108 | 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 |
| Nevada Cancer Research Foundation CCOP | Las Vegas | Nevada | 89106 | United States |
| Hackensack University Medical Center | Hackensack | New Jersey | 07601 | United States |
| Saint Peter's University Hospital | New Brunswick | New Jersey | 08901 | United States |
| UMDNJ - Robert Wood Johnson University Hospital | New Brunswick | New Jersey | 08903 | United States |
| Newark Beth Israel Medical Center | Newark | New Jersey | 07112 | United States |
| Roswell Park Cancer Institute | Buffalo | New York | 14263 | United States |
| Columbia University Medical Center | New York | New York | 10032 | United States |
| Memorial Sloan-Kettering Cancer Center | New York | New York | 10065 | United States |
| University of Rochester | Rochester | New York | 14642 | United States |
| State University of New York Upstate Medical University | Syracuse | New York | 13210 | United States |
| Ny Cancer% | Valhalla | New York | 10595 | United States |
| University of North Carolina | Chapel Hill | North Carolina | 27599 | United States |
| Carolinas Medical Center | Charlotte | North Carolina | 28203 | United States |
| Duke University Medical Center | Durham | North Carolina | 27710 | United States |
| Sanford Medical Center-Fargo | Fargo | North Dakota | 58122 | United States |
| Children's Hospital Medical Center of Akron | Akron | Ohio | 44308 | United States |
| Cleveland Clinic Foundation | Cleveland | Ohio | 44195 | United States |
| Nationwide Children's Hospital | Columbus | Ohio | 43205 | United States |
| University of Oklahoma Health Sciences Center | Oklahoma City | Oklahoma | 73104 | United States |
| Legacy Emanuel Hospital and Health Center | Portland | Oregon | 97227 | United States |
| Oregon Health and Science University | Portland | Oregon | 97239 | United States |
| Penn State Hershey 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 |
| Palmetto Health Richland | Columbia | South Carolina | 29203 | United States |
| St. Jude Children's Research Hospital | Memphis | Tennessee | 38105 | United States |
| Vanderbilt-Ingram Cancer Center | Nashville | Tennessee | 37232 | United States |
| University of Texas Southwestern Medical Center | Dallas | Texas | 75390 | United States |
| Cook Children's Medical Center | Fort Worth | Texas | 76104 | United States |
| Baylor College of Medicine | Houston | Texas | 77030 | United States |
| Covenant Children's Hospital | Lubbock | Texas | 79410 | United States |
| University of Texas Health Science Center at San Antonio | San Antonio | Texas | 78229-3900 | United States |
| Primary Children's Hospital | Salt Lake City | Utah | 84113 | United States |
| University of Vermont | Burlington | Vermont | 05401 | United States |
| Childrens Hospital-King's Daughters | Norfolk | Virginia | 23507 | United States |
| Seattle Children's Hospital | Seattle | Washington | 98105 | United States |
| Mary Bridge Children's Hospital and Health Center | Tacoma | Washington | 98405 | United States |
| Midwest Children's Cancer Center | Milwaukee | Wisconsin | 53226 | United States |
| Princess Margaret Hospital for Children | Perth | Western Australia | 6008 | Australia |
| 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 |
| Cancer Centre of Southeastern Ontario at Kingston General Hospital | Kingston | Ontario | K7L 5P9 | 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 |
| San Jorge Children's Hospital | Santurce | 00912 | Puerto Rico |
| COMPLETED |
|
| NOT COMPLETED |
|
|
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Treatment (Combination Chemotherapy) | INDUCTION THERAPY COURSE I: Patients receive cytarabine IT on day 1 and cytarabine IV continuously over 96 hours, daunorubicin hydrochloride IV continuously, and oral thioguanine BID on days 1-4. COURSE II: Patients receive high-dose cytarabine IV over 3 hours BID on days 1, 2, 8, and 9 and asparaginase (IM) on days 2 and 9. COURSE III: Patients receive treatment as in course I. COURSE IV: Patients receive cytarabine IV, daunorubicin hydrochloride IV, and oral thioguanine as in course I INTENSIFICATION THERAPY: Patients receive cytarabine IV continuously over 168 hours on days 1-7 and etoposide IV over 1 hour on days 1-3. Treatment repeats every 28 days for 2 courses in the absence of disease progression or unacceptable toxicity. asparaginase: Given IM daunorubicin hydrochloride: Given IV cytarabine: Given IV or IT thioguanine: Given orally etoposide: Given IV laboratory biomarker analysis: Correlative studies |
| 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 | days |
| ||||||||||||||||||||||
| Age, Categorical | Count of Participants | Participants |
| |||||||||||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| |||||||||||||||||||||||
| Race (NIH/OMB) | Count of Participants | Participants |
| |||||||||||||||||||||||
| Ethnicity (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) at 3 Years | Ineligible patients are excluded from analyses of event free survival and overall survival. | Posted | Number | 95% Confidence Interval | percentage | Time from study entry to induction failure, relapse, or death assessed at 3 years. |
|
|
| ||||||||||||||||||||||||||
| Primary | Overall Survival (OS) at 3 Years | Ineligible patients are excluded from analyses of overall survival and event free survival. | Posted | Number | 95% Confidence Interval | percentage | Time from study entry to death, assessed at 3 years. |
|
| |||||||||||||||||||||||||||
| Secondary | Induction Remission Rate | Proportion of participants with a remission after four courses of Induction therapy. | Ineligible (n=1) patients are excluded. Patients who withdrew from therapy before completing 4 courses of Induction and did not die or relapse are not evaluable (n=9) for Induction remission rate. | Posted | Number | Proportion of participants | End of induction therapy (day 112) |
|
| |||||||||||||||||||||||||||
| Secondary | Percentage of Patients Experiencing Grade 3 or 4 Toxicity Assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 | Proportion of participants with at least one grade 3 or higher adverse event during therapy. | Ineligible patients (n=1) are excluded. | Posted | Number | Proportion of participants | From the beginning of induction therapy to the end of intensification therapy |
|
| |||||||||||||||||||||||||||
| Secondary | Prevalence of Leukemia Phenotype of DS Patients < 4 Years of Age at Diagnosis by Flow Cytometry | Proportion of participants having megakaryoblastic subtype (AMkL) phenotype among patients with phenotype data available. | Ineligible patients (n=1) are excluded. Patients without available or evaluable phenotype data are excluded (n=40). Data are not available at end of therapy or relapse. | Posted | Number | Proportion of participants | At the start of therapy |
|
| |||||||||||||||||||||||||||
| Secondary | Prevalence of of GATA1 Mutations of DS Patients < 4 Years of Age at Diagnosis | Proportion of participants having GATA1 mutation among patients with phenotype data available. | Ineligible patients (n=1) are excluded. Patients without available or evaluable phenotype data are excluded (n=158). Data are not available at end of therapy or relapse. | Posted | Number | Proportion of participants | At baseline and at the end of therapy (intensification) or disease relapse |
|
| |||||||||||||||||||||||||||
| Secondary | Proportions of Patients in Morphologic Remission With Positive MRD by Flow Cytometry | Proportion of participants in complete remission by morphology and with positive MRD by flow cytometry among patients having evaluable remission and MRD assessment. | Ineligible patients (n=1) are excluded. Patients without available MRD at end of Induction I (n=58) or not evaluable for morphologic remission assessment (n=7) are excluded. MRD data are not available at end of Induction IV or after completion of Intensification therapy. | Posted | Number | Proportion of participants | After Induction I therapy (day 28 from start of therapy) |
| ||||||||||||||||||||||||||||
| Secondary | Cytarabine Drug Sensitivity by R-Strip (MicroMath) Curve Fitting Program | Mean and standard deviation of peak plasma concentration. Specimen draws were performed only with dose 1, day 1 of induction II of AraC. First sample drawn pre-infusion, then drawn 30 mins prior to the end of the infusion, and then drawn for 6 time periods post infusion up to 8 hours post infusion (and before the 2nd dose of AraC). Results are based from these multiple time points on Day 1 of Induction II only. | Ineligible patients (n=1) are excluded. Patients without available data from peak plasma concentration (n=146) are excluded. | Posted | Mean | Standard Deviation | Mean micromolar | Days 1, 2, 8, and 9 of induction II |
| |||||||||||||||||||||||||||
| Secondary | Cytarabine Drug Sensitivity by R-Strip (MicroMath) Curve Fitting Program | Mean and standard deviation of area under the concentration time curve. Specimen draws were performed only with dose 1, day 1 of induction II of AraC. First sample drawn pre-infusion, then drawn 30 mins prior to the end of the infusion, and then drawn for 6 time periods post infusion up to 8 hours post infusion (and before the 2nd dose of AraC). Results are based from these multiple time points on Day 1 of Induction II only. | Ineligible patients (n=1) are excluded. Patients without available data for area under the concentration time curve (n=146) are excluded. | Posted | Mean | Standard Deviation | Mean micromolar x minutes | Days 1, 2, 8, and 9 of induction II |
| |||||||||||||||||||||||||||
| Secondary | Cytarabine Drug Sensitivity by R-Strip (MicroMath) Curve Fitting Program | Mean and standard deviation of half-life of elimination. Specimen draws were performed only with dose 1, day 1 of induction II of AraC. First sample drawn pre-infusion, then drawn 30 mins prior to the end of the infusion, and then drawn for 6 time periods post infusion up to 8 hours post infusion (and before the 2nd dose of AraC). Results are based from these multiple time points on Day 1 of Induction II only. | Ineligible patients (n=1) are excluded. Patients without available data for half-life of elimination (n=146) are excluded. | Posted | Mean | Standard Deviation | Mean minutes | Days 1, 2, 8, and 9 of induction II |
| |||||||||||||||||||||||||||
| Secondary | Gene Expression Profiles by Microarrays | A hierarchical clustering algorithm is used to assemble the genes into a dendrogram or tree structure with branches containing genes with similar patterns of expression. This ordered representation can be graphically displayed with colors that reflect the qualitative and quantitative relationships of the expressed genes. | The Microarray analysis secondary outcome is not available because the number of specimens with good quality wasn't sufficient to yield meaningful results. | Posted | At baseline and at the time of relapse (if available) |
|
Not provided
SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.
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 | Treatment (Combination Chemotherapy) | INDUCTION THERAPY COURSE I: Patients receive cytarabine IT on day 1 and cytarabine IV continuously over 96 hours, daunorubicin hydrochloride IV continuously, and oral thioguanine BID on days 1-4. COURSE II: Patients receive high-dose cytarabine IV over 3 hours BID on days 1, 2, 8, and 9 and asparaginase (IM) on days 2 and 9. COURSE III: Patients receive treatment as in course I. COURSE IV: Patients receive cytarabine IV, daunorubicin hydrochloride IV, and oral thioguanine as in course I INTENSIFICATION THERAPY: Patients receive cytarabine IV continuously over 168 hours on days 1-7 and etoposide IV over 1 hour on days 1-3. Treatment repeats every 28 days for 2 courses in the absence of disease progression or unacceptable toxicity. asparaginase: Given IM daunorubicin hydrochloride: Given IV cytarabine: Given IV or IT thioguanine: Given orally etoposide: Given IV laboratory biomarker analysis: Correlative studies | 3 | 204 | 185 | 204 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Ascites | Gastrointestinal disorders |
| |||
| Hepatic failure | Hepatobiliary disorders |
| |||
| Hypoxia | Respiratory, thoracic and mediastinal disorders |
| |||
| Immune system disorders - Other | Immune system disorders |
| |||
| Respiratory, thoracic and mediastinal disorders - Other | Respiratory, thoracic and mediastinal disorders |
| |||
| Typhlitis | Gastrointestinal disorders |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abdominal pain | Gastrointestinal disorders |
| |||
| Acidosis | Metabolism and nutrition disorders |
| |||
| Activated partial thromboplastin time prolonged | Investigations |
| |||
| Acute kidney injury | Renal and urinary disorders |
| |||
| Adult respiratory distress syndrome | Respiratory, thoracic and mediastinal disorders |
| |||
| Alanine aminotransferase increased | Investigations |
| |||
| Alkalosis | Metabolism and nutrition disorders |
| |||
| Anal pain | Gastrointestinal disorders |
| |||
| Anaphylaxis | Immune system disorders |
| |||
| Anemia | Blood and lymphatic system disorders |
| |||
| Anorectal infection | Infections and infestations |
| |||
| Anorexia | Metabolism and nutrition disorders |
| |||
| Apnea | Respiratory, thoracic and mediastinal disorders |
| |||
| Aspartate aminotransferase increased | Investigations |
| |||
| Aspiration | Respiratory, thoracic and mediastinal disorders |
| |||
| Bladder infection | Infections and infestations |
| |||
| Blood and lymphatic system disorders - Other | Blood and lymphatic system disorders |
| |||
| Blood bilirubin increased | Investigations |
| |||
| Cardiac arrest | Cardiac disorders |
| |||
| Cardiac disorders - Other | Cardiac disorders |
| |||
| Catheter related infection | Infections and infestations |
| |||
| Colitis | Gastrointestinal disorders |
| |||
| Conjunctivitis infective | Infections and infestations |
| |||
| Dehydration | Metabolism and nutrition disorders |
| |||
| Device related infection | Infections and infestations |
| |||
| Diarrhea | Gastrointestinal disorders |
| |||
| Disseminated intravascular coagulation | Blood and lymphatic system disorders |
| |||
| Dysphagia | Gastrointestinal disorders |
| |||
| Dyspnea | Respiratory, thoracic and mediastinal disorders |
| |||
| Electrocardiogram QT corrected interval prolonged | Investigations |
| |||
| Encephalopathy | Nervous system disorders |
| |||
| Endocarditis infective | Infections and infestations |
| |||
| Enterocolitis infectious | Infections and infestations |
| |||
| Epistaxis | Respiratory, thoracic and mediastinal disorders |
| |||
| Esophagitis | Gastrointestinal disorders |
| |||
| Eye infection | Infections and infestations |
| |||
| Fatigue | General disorders |
| |||
| Febrile neutropenia | Blood and lymphatic system disorders |
| |||
| Fever | General disorders |
| |||
| Gastritis | Gastrointestinal disorders |
| |||
| Gastrointestinal disorders - Other | Gastrointestinal disorders |
| |||
| GGT increased | Investigations |
| |||
| Gum infection | Infections and infestations |
| |||
| Hyperglycemia | Metabolism and nutrition disorders |
| |||
| Hyperkalemia | Metabolism and nutrition disorders |
| |||
| Hypertension | Vascular disorders |
| |||
| Hypoalbuminemia | Metabolism and nutrition disorders |
| |||
| Hypocalcemia | Metabolism and nutrition disorders |
| |||
| Hypoglycemia | Metabolism and nutrition disorders |
| |||
| Hypokalemia | Metabolism and nutrition disorders |
| |||
| Hypomagnesemia | Metabolism and nutrition disorders |
| |||
| Hyponatremia | Metabolism and nutrition disorders |
| |||
| Hypophosphatemia | Metabolism and nutrition disorders |
| |||
| Hypotension | Vascular disorders |
| |||
| Hypoxia | Respiratory, thoracic and mediastinal disorders |
| |||
| Infections and infestations - Other | Infections and infestations |
| |||
| Investigations - Other | Investigations |
| |||
| Irritability | General disorders |
| |||
| Laryngeal edema | Respiratory, thoracic and mediastinal disorders |
| |||
| Lipase increased | Investigations |
| |||
| Lung infection | Infections and infestations |
| |||
| Lymphocyte count decreased | Investigations |
| |||
| Malabsorption | Gastrointestinal disorders |
| |||
| Metabolism and nutrition disorders - Other | Metabolism and nutrition disorders |
| |||
| Mucositis oral | Gastrointestinal disorders |
| |||
| Nausea | Gastrointestinal disorders |
| |||
| Nervous system disorders - Other | Nervous system disorders |
| |||
| Neutrophil count decreased | Investigations |
| |||
| Oral hemorrhage | Gastrointestinal disorders |
| |||
| Oral pain | Gastrointestinal disorders |
| |||
| Otitis externa | Infections and infestations |
| |||
| Otitis media | Infections and infestations |
| |||
| Pain | General disorders |
| |||
| Pain of skin | Skin and subcutaneous tissue disorders |
| |||
| Pericardial effusion | Cardiac disorders |
| |||
| Pharyngeal mucositis | Respiratory, thoracic and mediastinal disorders |
| |||
| Photophobia | Eye disorders |
| |||
| Platelet count decreased | Investigations |
| |||
| Pleural effusion | Respiratory, thoracic and mediastinal disorders |
| |||
| Pneumonitis | Respiratory, thoracic and mediastinal disorders |
| |||
| Purpura | Skin and subcutaneous tissue disorders |
| |||
| Rash maculo-papular | Skin and subcutaneous tissue disorders |
| |||
| Respiratory, thoracic and mediastinal disorders - Other | Respiratory, thoracic and mediastinal disorders |
| |||
| Seizure | Nervous system disorders |
| |||
| Sepsis | Infections and infestations |
| |||
| Serum amylase increased | Investigations |
| |||
| Sinus tachycardia | Cardiac disorders |
| |||
| Sinusitis | Infections and infestations |
| |||
| Skin infection | Infections and infestations |
| |||
| Small intestine infection | Infections and infestations |
| |||
| Soft tissue infection | Infections and infestations |
| |||
| Stridor | Respiratory, thoracic and mediastinal disorders |
| |||
| Typhlitis | Gastrointestinal disorders |
| |||
| Upper gastrointestinal hemorrhage | Gastrointestinal disorders |
| |||
| Upper respiratory infection | Infections and infestations |
| |||
| Urinary tract infection | Infections and infestations |
| |||
| Vascular access complication | Injury, poisoning and procedural complications |
| |||
| Vomiting | Gastrointestinal disorders |
| |||
| Vulval infection | Infections and infestations |
| |||
| Weight loss | Investigations |
| |||
| White blood cell decreased | Investigations |
|
Must obtain prior Sponsor approval.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Results Reporting Coordinator | Children's Oncology Group | 626-447-0064 | resultsreportingcoordintator@childrensoncologygroup.org |
| ID | Term |
|---|---|
| D015472 | Leukemia, Eosinophilic, Acute |
| ID | Term |
|---|---|
| D015470 | Leukemia, Myeloid, Acute |
| D007951 | Leukemia, Myeloid |
| D007938 | Leukemia |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| D001215 | Asparaginase |
| C087753 | palmitoyl-L-asparaginase |
| D003630 | Daunorubicin |
| D003561 | Cytarabine |
| D013866 | Thioguanine |
| D005047 | Etoposide |
| ID | Term |
|---|---|
| D000581 | Amidohydrolases |
| D006867 | Hydrolases |
| D004798 | Enzymes |
| D045762 | Enzymes and Coenzymes |
| D018943 | Anthracyclines |
| D009279 | Naphthacenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D011083 | Polycyclic Compounds |
| D000617 | Aminoglycosides |
| D006027 | Glycosides |
| D002241 | Carbohydrates |
| 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 |
| D011687 | Purines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D011034 | Podophyllotoxin |
| D013764 | Tetrahydronaphthalenes |
| D009281 | Naphthalenes |
| D005960 | Glucosides |
Not provided
Not provided
| >=65 years |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
| Unknown or Not Reported |
|
| Australia |
|
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