Clinical Trial: Decitabine, Vorinostat, and Cytarabine in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Phase I Study of Decitabine, Vorinostat, and Cytarabine in Acute Myeloid Leukemia

Brief Summary: This phase I trial is studying the side effects and the best dose of cytarabine when given together with decitabine and vorinostat in treating patients with relapsed or refractory acute myeloid leukemia. Drugs used in chemotherapy, such as cytarabine and decitabine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Vorinostat may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving cytarabine together with decitabine and vorinostat may kill more cancer cells.

Detailed Summary:

PRIMARY OBJECTIVES:

I. To determine the maximum tolerated dose (MTD) of the combination of decitabine, vorinostat, and cytarabine in patients with relapsed/refractory acute myeloid leukemia (AML) and select subsets of high risk leukemia/myelodysplastic syndromes (MDS).

II. To define the specific toxicities and the dose limiting toxicity (DLT) of the combination.

SECONDARY OBJECTIVES:

I. To develop a platform for specifically targeting MLL PTD, for future efficacy studies.

II. To determine the overall response rate (ORR) of this regimen in relapsed/ refractory AML.

III. To examine the role of decitabine and vorinostat in re-expression of MLL- WT in patients with MLL PTD via correlative studies specific to patients with MLL PTD and the preliminary relationship of this to clinical response in patients with MLL PTD+ AML.

IV. To correlate the biological activity of decitabine as demethylating agent (changes in target gene methylation and gene expression, DNMT1 protein expression, global methylation) with clinical endpoints V. To explore the biologic role of microRNAs in determining clinical response to the combination and achievement of the other pharmacodynamic endpoints.

OUTLINE: This is a dose-escalation study of cytarabine.

INDUCTION THERAPY: Patients receive decitabine IV over 1 hour on days 1-10; oral vorinostat on days 5-10; and high-dose cytarabine IV over 2 hours on days 12, 14, and 16 in the absence of disease progression or unacceptable toxicity. Patients who achieve comple
Sponsor: National Cancer Institute (NCI)

Current Primary Outcome:

  • MTD of decitabine and vorinostat, determined according to incidence of DLT graded using NCI CTCAE version 4.0 [ Time Frame: 28 days ]
  • Toxicity, graded according to NCI CTCAE version 4.0 [ Time Frame: Up to 30 days after completion of study treatment ]


Original Primary Outcome:

  • Maximum-tolerated dose
  • Toxicity
  • Dose-limiting toxicity


Current Secondary Outcome: Overall response rate, assessed using International Working Group criteria [ Time Frame: Up to 30 days after completion of study treatment ]

Original Secondary Outcome:

  • Overall response rate
  • Role of decitabine and vorinostat in re-expression of MLL- WT in patients with MLL PTD
  • Correlation between biological activity of decitabine with clinical endpoints


Information By: National Cancer Institute (NCI)

Dates:
Date Received: May 25, 2010
Date Started: May 2010
Date Completion:
Last Updated: December 19, 2014
Last Verified: June 2014