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

Study Status: Terminated
Recruit Status: Terminated
Study Type: Interventional

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

Brief 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

Detailed Summary:

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
Sponsor: National Cancer Institute (NCI)

Current Primary Outcome: MTD defined as the highest dose at which fewer than one-third of patients experience DLT assessed using CTC version 2.0 [ Time Frame: 4 weeks ]

Original Primary Outcome:

Current Secondary Outcome:

  • CR rate [ Time Frame: Up to 3 years ]
    Will be estimated by proportions.
  • PR rate [ Time Frame: Up to 3 years ]
    Will be estimated by proportions.
  • DNA methylation [ Time Frame: Up to 3 years ]
    Pearson correlation will be used.
  • Gene expression profiles [ Time Frame: Up to 3 years ]
    Will be analyzed using hierarchical clustering.
  • HDAC/HAT activity [ Time Frame: Up to 3 years ]
    Pearson correlation coefficient analysis will be used.
  • Presence of mutant helicases [ Time Frame: Up to 3 years ]


Original Secondary Outcome:

Information By: National Cancer Institute (NCI)

Dates:
Date Received: August 5, 2002
Date Started: December 2002
Date Completion:
Last Updated: January 22, 2013
Last Verified: January 2013