Combination Chemotherapy in Treating Young Patients With Down Syndrome and Acute Myeloid Leukemia or Myelodysplastic Syndromes
|Childhood Acute Basophilic Leukemia Childhood Acute Eosinophilic Leukemia Childhood Acute Erythroleukemia (M6) Childhood Acute Megakaryocytic Leukemia (M7) Childhood Acute Minimally Differentiated Myeloid Leukemia (M0) Childhood Acute Monoblastic Leukemia (M5a) Childhood Acute Monocytic Leukemia (M5b) Childhood Acute Myeloblastic Leukemia With Maturation (M2) Childhood Acute Myeloblastic Leukemia Without Maturation (M1) Childhood Acute Myelomonocytic Leukemia (M4) Childhood Myelodysplastic Syndromes de Novo Myelodysplastic Syndromes Secondary Acute Myeloid Leukemia Secondary Myelodysplastic Syndromes Untreated Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies||Drug: asparaginase Drug: daunorubicin hydrochloride Drug: cytarabine Drug: thioguanine Drug: etoposide Other: laboratory biomarker analysis||Phase 3|
|Study Design:||Intervention Model: Single Group Assignment
Masking: No masking
Primary Purpose: Treatment
|Official Title:||The Treatment of Down Syndrome Children With Acute Myeloid Leukemia (AML) and Myelodysplastic Syndromes (MDS) Under the Age of 4 Years|
- Event-free Survival (EFS) at 3 Years [ Time Frame: Time from study entry to induction failure, relapse, or death assessed at 3 years. ]
- Overall Survival (OS) at 3 Years [ Time Frame: Time from study entry to death, assessed at 3 years. ]
- Induction Remission Rate [ Time Frame: End of induction therapy ]
- 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 [ Time Frame: 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 [ Time Frame: At baseline and at the end of therapy (intensification) or disease relapse ]The prevalence of megakaryoblastic subtype (AMkL) phenotype will be estimated as the proportion of patients with phenotype data available determined to have the AMkL phenotype. EFS will be estimated for those with and without AMkL using the approach of Kaplan and Meier. Differences in these estimates will be tested for significance using the log-rank statistic test.
- Prevalence of of GATA1 Mutations of DS Patients < 4 Years of Age at Diagnosis [ Time Frame: At baseline and at the end of therapy (intensification) or disease relapse ]The prevalence of GATA1 mutations will be estimated as the proportion of patients with phenotype data available determined to have the GATA1 mutations.
- Proportions of Patients in Morphologic Remission With Positive MRD by Flow Cytometry [ Time Frame: After completion of induction therapy (I, IV) and after completion of intensification therapy ]Differences in the cumulative incidence of relapse for those with and without MRD will be tested using Gray's test.
- Cytarabine Drug Sensitivity by R-Strip (MicroMath) Curve Fitting Program. [ Time Frame: Days 1, 2, 8, and 9 of induction II ]Descriptive statistics will be used to summarize pharmacokinetic parameters, such as peak plasma concentration, area under the concentration time curve, and half-life of elimination
- Gene Expression Profiles by Microarrays [ Time Frame: At baseline and at the time of relapse (if available) ]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.
|Study Start Date:||March 2007|
|Study Completion Date:||December 2013|
|Primary Completion Date:||December 2013 (Final data collection date for primary outcome measure)|
Experimental: 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.
Other Names:Drug: daunorubicin hydrochloride
Other Names:Drug: cytarabine
Given IV or IT
Other Names:Drug: thioguanine
Other Name: 6-TGDrug: etoposide
Other Names:Other: laboratory biomarker analysis
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00369317
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|Principal Investigator:||Jeffrey Taub, MD||Children's Oncology Group|