Azacitidine With or Without Entinostat in Treating Patients With Myelodysplastic Syndromes, Chronic Myelomonocytic Leukemia, or Acute Myeloid Leukemia
This randomized phase II trial is studying azacitidine and entinostat to see how well they work compared to azacitidine alone in treating patients with myelodysplastic syndromes, chronic myelomonocytic leukemia, or acute myeloid leukemia. Both treatment-induced and non-treatment-induced cohorts are allowed. Drugs used in chemotherapy, such as azacitidine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Entinostat may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving azacitidine together with entinostat may kill more cancer cells.
Chronic Myelomonocytic Leukemia (Dysplastic Type)
Acute Myeloid Leukemia With Multilineage Dysplasia
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Randomized Phase II Trial of Azacitidine With or Without the Histone Deacetylase Inhibitor Entinostat for the Treatment of Myelodysplastic Syndrome, Chronic Myelomonocytic Leukemia (Dysplastic Type), and Acute Myeloid Leukemia With Multilineage Dysplasia|
- Proportion of Patients With Clinical Response [ Time Frame: Assessed every 3 months if patient is < 2 years from study entry, every 6 months if patient is 2 - 5 years from study entry. ] [ Designated as safety issue: No ]
Clinical response is defined as a complete response (CR), partial response (PR) or trilineage response (TR) graded according to the following criteria:
- World Health Organization classification of the acute leukemias and myelodysplastic syndrome (by Bennett)
- Myelodysplastic syndromes standardized response criteria: further definition (by Cheson et al.)
- Report of an international working group to standardize response criteria for myelodysplastic syndromes (by Cheson et al.)
|Study Start Date:||August 2006|
|Estimated Study Completion Date:||April 2016|
|Primary Completion Date:||July 2013 (Final data collection date for primary outcome measure)|
Experimental: Arm A
Patients receive azacitidine (50 mg/m2) subcutaneously once daily on days 1-10 in a 28-day cycle.
Experimental: Arm B
Patients receive azacitidine as in arm A and oral entinostat (4 mg/m2) on days 3 and 10 of each 28-day cycle.
Other Names:Drug: azacitidine
I. To estimate the response rate (complete, partial, and trilineage response) in both treatment arms for the two cohorts
I. Evaluate the toxicity of azacitidine and entinostat in these patients.
II. Identify changes in gene promoter methylation and gene expression that may be associated with response to azacitidine and entinostat.
III. Identify other molecular mechanisms (such as DNA damage) that may be associated with response to azacitidine and entinostat.
OUTLINE: This is a randomized, multicenter study. Two groups of patients, treatment-induced cohort and non-treatment-induced cohort, are enrolled on this study. Patients are stratified according to disease (myelodysplastic syndromes [MDS] high/intermediate-2 vs MDS low/intermediate-1 vs chronic myelomonocytic leukemia vs acute myeloid leukemia with multilineage dysplasia). Both cohorts are randomized to 1 of 2 treatment arms.
ARM A: Patients receive azacitidine subcutaneously once daily on days 1-10.
ARM B: Patients receive azacitidine as in arm A and oral entinostat on days 3 and 10.
Treatment in both arms repeats every 28 days for at least 6 and up to 24 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed periodically for 5 years.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00313586
Show 232 Study Locations
|Study Chair:||Steven Gore, M.D.||Sidney Kimmel Comprehensive Cancer Center|