Clinical trial NCT00313586
Conditions: 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
Sponsor: National Cancer Institute (NCI)
Start date: 2006-08-01; Completion date: 2013-07-01
Enrollment: 197 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
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.

Detailed description:
PRIMARY OBJECTIVES:

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.

SECONDARY OBJECTIVES:

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.

Arms: arm 1: 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. arm 2: 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.
Interventions: intervention 1: Azacitidine intervention 2: Entinostat intervention 3: Laboratory Biomarker Analysis
Intervention descriptions: intervention 1: Given SC intervention 2: Given PO intervention 3: Correlative studies

Protocol documents: