NCT00369317

Combination Chemotherapy in Treating Young Patients With Down Syndrome and Acute Myeloid Leukemia or Myelodysplastic Syndromes

The Treatment of Down Syndrome Children With Acute Myeloid Leukemia (AML) and Myelodysplastic Syndromes (MDS) Under the Age of 4 Years

• Status: Completed
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 205 (actual)
• Sponsor: Children's Oncology Group · Network
• Sex: All
• Age: 4 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

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.

Conditions

• 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

Interventions

Type	Name	Description
DRUG	asparaginase	Given IM
DRUG	daunorubicin hydrochloride	Given IV
DRUG	cytarabine	Given IV or IT
DRUG	thioguanine	Given orally
DRUG	etoposide	Given IV
OTHER	laboratory biomarker analysis	Correlative studies

Timeline

• Start date: 2007-03-01
• Primary completion: 2013-12-01
• Completion: 2021-12-31
• First posted: 2006-08-29
• Last updated: 2022-01-28
• Results posted: 2015-01-13

Locations

97 sites across 4 countries: United States, Australia, Canada, Puerto Rico