Azacitidine With or Without Entinostat in Treating Patients With Myelodysplastic Syndromes, Chronic Myelomonocytic Leukemia, or Acute Myeloid Leukemia
This randomized phase II trial studies azacitidine with or without 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, by stopping them from dividing, or by stopping them from spreading. Entinostat may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving azacitidine together with entinostat may work better in treating patients with myelodysplastic syndromes, chronic myelomonocytic leukemia, or acute myeloid leukemia.
Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome
Adult Acute Myeloid Leukemia in Remission
Adult Acute Myeloid Leukemia With Inv(16)(p13.1q22); CBFB-MYH11
Adult Acute Myeloid Leukemia With t(16;16)(p13.1;q22); CBFB-MYH11
Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); RUNX1-RUNX1T1
Adult Acute Myeloid Leukemia With t(9;11)(p22;q23); MLLT3-MLL
Adult Acute Promyelocytic Leukemia With t(15;17)(q22;q12); PML-RARA
Alkylating Agent-Related Acute Myeloid Leukemia
Chronic Myelomonocytic Leukemia
de Novo Myelodysplastic Syndrome
Previously Treated Myelodysplastic Syndrome
Recurrent Adult Acute Myeloid Leukemia
Secondary Acute Myeloid Leukemia
Secondary Myelodysplastic Syndrome
Untreated Adult Acute Myeloid Leukemia
Other: Laboratory Biomarker Analysis
|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 (azacitidine)
Patients receive azacitidine SC QD on days 1-10. Treatment repeats every 28 days for 6-24 courses in the absence of disease progression or unacceptable toxicity.
Other Names:Other: Laboratory Biomarker Analysis
Experimental: Arm B (azacitidine, entinostat)
Patients receive azacitidine as in Arm A and entinostat PO on days 3 and 10. Treatment repeats every 28 days for 6-24 courses in the absence of disease progression or unacceptable toxicity.
Other Names:Drug: Entinostat
Other Names:Other: Laboratory Biomarker Analysis
I. To estimate the overall response rate (complete, partial, and hematologic improvement-major by International Working Group [IWG] criteria) in response to azacitidine and entinostat.
II. To estimate the major response rate (complete and partial responses by the IWG response criteria) to a 10-day regimen of azacitidine and to the same regimen of azacitidine in combination with entinostat administered orally on days 3 and 10 of each cycle in patients with de novo myelodysplastic syndromes (MDS), chronic myelomonocytic leukemia (CMMoL) (dysplastic) and acute myeloid leukemia with trilineage dysplasia (AML-TLD), as well as in patients with treatment-induced MDS, CMMoL (dysplastic) and AML-TLD.
I. To evaluate the toxicity of azacitidine and entinostat in this patient population.
II. To identify changes in gene promoter methylation and gene expression which may be associated with response to azacitidine and entinostat.
III. To identify other molecular mechanisms (such as deoxyribonucleic acid [DNA] damage) which may be associated with response to azacitidine and entinostat.
OUTLINE: Patients are randomized to 1 of 2 treatment arms.
ARM A: Patients receive azacitidine subcutaneously (SC) once daily (QD) on days 1-10.
ARM B: Patients receive azacitidine as in Arm A and entinostat orally (PO) on days 3 and 10.
In both arms, treatment repeats every 28 days for 6-24 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for 5 years.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00313586
Show 234 Study Locations
|Principal Investigator:||Steven Gore||ECOG-ACRIN Cancer Research Group|