Decitabine in Treating Children With Relapsed or Refractory Acute Myeloid Leukemia or Acute Lymphoblastic Leukemia

Secondary Acute Myeloid Leukemia Clinical Trial

Official title: A Phase I Study Of Decitabine (DAC) (IND # 50733) In Children With Relapsed Or Refractory Acute Leukemia

Status Terminated

Clinical Trial Summary

Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. This phase I trial is studying the side effects and best dose of decitabine in treating children with relapsed or refractory acute myeloid leukemia or acute lymphoblastic leukemia

Clinical Trial Description

PRIMARY OBJECTIVES:

I. Determine the maximum tolerated dose of decitabine that is associated with consistent evidence of deoxyribonucleic acid (DNA) demethylation in children with relapsed or refractory acute myeloid leukemia or acute lymphoblastic leukemia.

II. Determine the dose-limiting toxicity, pharmacokinetics, and antitumor activity of this drug in these patients.

III. Determine the biologic correlates of decitabine-induced DNA demethylation by characterizing, before and after treatment, global and specific DNA methylation status (using methylation microarrays) and hemoglobin F levels in these patients.

IV. Determine the biologic correlates of decitabine-induced DNA demethylation by characterizing, before and after treatment, global changes in gene expression profiles using cDNA microarrays and drug sensitivity of blast cells by MTT assays in these patients.

V. Determine the biologic correlates of decitabine-induced DNA demethylation by characterizing, before and after treatment, deletions and single nucleotide polymorphisms in genomic DNA of deoxycytidine kinase and cytidine deaminase genes in these patients.

VI. Determine the biologic correlates of decitabine-induced DNA demethylation by characterizing, before and after treatment, acetylation and methylation of histones H3 and H4 and helicase protein expression in these patients.

OUTLINE: This is a dose-escalation, multicenter study. Patients are stratified according to disease type (acute myeloid leukemia vs acute lymphoblastic leukemia).

Patients receive decitabine IV over 1 hour on days 1-5 and 8-12. Treatment repeats every 4-6 weeks for a minimum of 4 courses in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of decitabine until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

PROJECTED ACCRUAL: A total of 15-21 patients will be accrued for this study within 7.5-21 months. ;

Study Design

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Childhood Acute Myeloblastic Leukemia With Maturation (M2)
• Childhood Acute Promyelocytic Leukemia (M3)
• Leukemia
• Leukemia, Lymphoid
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Leukemia, Promyelocytic, Acute
• Precursor Cell Lymphoblastic Leukemia-Lymphoma
• Recurrent Childhood Acute Lymphoblastic Leukemia
• Recurrent Childhood Acute Myeloid Leukemia
• Secondary Acute Myeloid Leukemia

• NCT number: NCT00042796
• Study type: Interventional
• Source: National Cancer Institute (NCI)
• Status: Terminated
• Phase: Phase 1
• Start date: December 2002