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. 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
de Novo Myelodysplastic Syndromes
Previously Treated Myelodysplastic Syndromes
Untreated Adult Acute Myeloid Leukemia
|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|
- The complete response rate, partial response rate, and trilineage response rate [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]Graded according to standard international response criteria.
- Overall response rate (complete response and partial response) [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]Graded according to standard international response criteria. Summarized by treatment arm in each cohort.
- Rate of grade 3 or 4 non-hematologic toxicity thought to be possibly or likely related to study drugs, graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 [ Time Frame: Up to 5 years ] [ Designated as safety issue: Yes ]Summarized by treatment arm in each cohort.
- Percentage of patients treated and become appropriate candidates for allogeneic transplant [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]Summarized by treatment arm in each cohort.
|Study Start Date:||August 2006|
|Estimated Primary Completion Date:||January 2100 (Final data collection date for primary outcome measure)|
Experimental: Arm I
Patients receive azacitidine subcutaneously once daily on days 1-10.
Experimental: Arm II
Patients receive azacitidine as in arm I and oral entinostat on days 3 and 10.
Other Names:Drug: azacitidine
I. Compare the overall response rate (complete, partial, and hematologic improvement-major by International Working Group [IWG] criteria) in patients with treatment-induced or non-treatment-induced myelodysplastic syndromes (MDS), chronic myelomonocytic leukemia (dysplastic), or acute myeloid leukemia with multilineage dysplasia treated with azacitidine with vs without entinostat.
II. Compare the major response rate (complete and partial responses by IWG criteria) in patients treated with these regimens.
I. Evaluate the toxicity of azacitidine and entinostatin 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. Patients are first stratified according to treatment-related disease (yes vs no), followed by a second stratification 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). Patients are randomized to 1 of 2 treatment arms.
ARM I: Patients receive azacitidine subcutaneously once daily on days 1-10.
ARM II: Patients receive azacitidine as in arm I 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.