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

2014-08-27 03:13:26 | BioPortfolio


RATIONALE: 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

PURPOSE: 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.




- To determine the maximum-tolerated dose of the combination of decitabine, vorinostat, and cytarabine in patients with relapsed or refractory acute myeloid leukemia (AML).

- To define the specific toxicities and the dose-limiting toxicity of this regimen in these patients.


- To determine the overall response rate in patients treated with this regimen.

- To develop a platform for specifically targeting mixed lineage leukemia partial tandem duplication (MLL PTD) for future efficacy studies.

- To examine the role of decitabine and vorinostat in re-expression of MLL- WT in patients with AML and MLL PTD.

- To determine the preliminary relationship of re-expression of MLL- WT to clinical response in these patients.

- 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.

- To explore the biologic role of microRNAs in determining clinical response to this regimen and achievement of the other pharmacodynamic endpoints.

OUTLINE: This 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 complete response (CR) proceed to maintenance therapy. Patients who achieve CR with incomplete blood count recovery undergo bone marrow aspiration and biopsy at count recovery or day 42 before proceeding to maintenance therapy.

- Maintenance therapy: Patients receive decitabine IV over 1 hour on days 1-5 and oral vorinostat on days 5-10. Treatment repeats every 28 days for up to 11 courses in the absence of disease progression or unacceptable toxicity.

Blood samples and additional bone marrow aspirate and biopsy are collected at baseline and during study for re-expression of MLL- WT, changes in target gene methylation and gene expression, DNMT1 protein expression, global methylation, and other pharmacodynamic studies.

After completion of study therapy, patients are followed up for 30 days.

Study Design

Masking: Open Label, Primary Purpose: Treatment




cytarabine, decitabine, vorinostat, gene expression analysis, protein expression analysis, laboratory biomarker analysis, pharmacological study


Not yet recruiting


National Cancer Institute (NCI)

Results (where available)

View Results


Published on BioPortfolio: 2014-08-27T03:13:26-0400

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