Azacitidine With or Without Entinostat in Treating Patients With Myelodysplastic Syndromes, Chronic Myelomonocytic Leukemia, or Acute Myeloid Leukemia
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|ClinicalTrials.gov Identifier: NCT00313586|
Recruitment Status : Completed
First Posted : April 12, 2006
Results First Posted : November 25, 2014
Last Update Posted : February 2, 2017
|Condition or disease||Intervention/treatment||Phase|
|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||Drug: Azacitidine Drug: Entinostat Other: Laboratory Biomarker Analysis||Phase 2|
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||197 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|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|
|Study Start Date :||August 2006|
|Actual Primary Completion Date :||July 2013|
|Actual Study Completion Date :||July 2013|
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: 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: Laboratory Biomarker Analysis
- 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. ]
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.)
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00313586
|Principal Investigator:||Steven Gore||ECOG-ACRIN Cancer Research Group|