Clinical Trial: Decitabine, Cytarabine, and Daunorubicin Hydrochloride in Treating Patients With Acute Myeloid Leukemia

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

Official Title: Randomized Phase II Study of Epigenetic Priming Using Decitabine With Induction Chemotherapy in Patients With Acute Myelogenous Leukemia (AML)

Brief Summary: This randomized phase II trial studies how well decitabine works when given together with daunorubicin hydrochloride and cytarabine in treating patients with acute myeloid leukemia. Drugs used in chemotherapy, such as decitabine, daunorubicin hydrochloride, and cytarabine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Decitabine may help daunorubicin hydrochloride and cytarabine kill more cancer cells by making them more sensitive to the drugs. It is not yet known whether low-dose decitabine is more effective than high-dose decitabine when giving together with daunorubicin hydrochloride and cytarabine in treating acute myeloid leukemia.

Detailed Summary:

OBJECTIVES: Primary I. To "Pick a Winner" by deciding whether further development of epigenetic priming with decitabine prior to standard "7+3" induction chemotherapy should be pursued.

Secondary I. To determine whether epigenetic priming with decitabine prior to standard cytarabine and daunorubicin hydrochloride "7+3" induction chemotherapy has sufficient efficacy to warrant further development as assessed by an overall CR1 rate ≥ 50%.

II. To establish the safety and expected toxicities of decitabine when used as priming for cytarabine and daunorubicin hydrochloride "7+3" induction chemotherapy in acute myeloid leukemia (AML).

III. To assess the pharmacodynamics of deoxyribonucleic acid (DNA) hypomethylation when decitabine is administered as a short infusion.

IV. To investigate, in selected cases, the molecular and cellular consequences of decitabine-induced hypomethylation by assessing the effects of decitabine-mediated hypomethylation on transcriptional patterns in AML cells, and by determining the effect of hypomethylation on the differentiation and/or apoptosis of leukemic blasts. (exploratory) V. To identify biomolecular correlates of treatment response (biomarkers) to induction chemotherapy in AML based upon the epigenetic pattern of DNA methylation in AML specimens obtained prior to treatment. (exploratory)

OUTLINE: This is a multicenter study. Patients are stratified according to age (less than 50 years vs 50-65 years), white blood cell count (≤ 30 K/mL vs greater than 30 K/mL), cytogenetic risk group (intermediate vs adverse risk), and antecedent hematological condition preceding the diagnosis of acute myeloid leu
Sponsor: National Cancer Institute (NCI)

Current Primary Outcome: Complete remission rate (CR1) [ Time Frame: After 1 course of decitabine-primed induction chemotherapy ]

Original Primary Outcome: Complete remission rate after one course of induction chemotherapy

Current Secondary Outcome:

  • Complete remission rate (CR1 + CR2) [ Time Frame: After up to 2 courses of decitabine-primed induction chemotherapy ]
  • Event-free survival [ Time Frame: Time from entry on study until treatment failure (no CR with up to two study induction cycles), AML relapse, or death from any cause, assessed up to 10 years ]
  • Overall survival [ Time Frame: Time from entry on study to time of death from any cause, assessed up to 10 years ]
  • Relapse-free survival [ Time Frame: Time from CR documentation to either AML relapse or death from any cause, assessed up to 10 years ]
  • Remission duration [ Time Frame: Time from CR documentation to either AML relapse, assessed up to 10 years ]
  • Time to complete response determined according to the International Working Group (IWG) criterion [ Time Frame: Time from entry on study until documentation of CR, up to second course of induction chemotherapy ]
    95% confidence limits will be provided.


Original Secondary Outcome:

  • Complete remission rate after up to two courses of induction chemotherapy
  • Overall survival
  • Relapse-free survival
  • Event-free survival
  • Time to complete response
  • Remission duration
  • Toxicity


Information By: National Cancer Institute (NCI)

Dates:
Date Received: June 21, 2012
Date Started: September 2011
Date Completion:
Last Updated: May 11, 2017
Last Verified: May 2017