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Clinical Trials (PDQ®)

Azacitidine With or Without Entinostat in Treating Patients With Myelodysplastic Syndromes, Chronic Myelomonocytic Leukemia, or Acute Myeloid Leukemia

Basic Trial Information
Trial Description
     Summary
     Further Trial Information
     Eligibility Criteria
Trial Contact Information

Basic Trial Information

PhaseTypeStatusAgeSponsorProtocol IDs
Phase IITreatmentClosed18 and overNCINCI-2009-01077
E1905, U10CA021115, ECOG-E1905, NCT00313586

Trial Description

Summary

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.

Further Study Information

PRIMARY OBJECTIVES:

I. To estimate the response rate (complete, partial, and trilineage response) in both treatment arms for the two cohorts

SECONDARY OBJECTIVES:

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.

Eligibility Criteria

Inclusion Criteria:

  • Bone marrow aspirate and/or biopsy-confirmed diagnosis of 1 of the following:
  • Myelodysplastic syndromes (MDS)
  • Any International Prognostic Score (IPSS) eligible
  • Patients with low or intermediate-1 IPSS must have platelet count < 50,000/mm³ and/or absolute neutrophil count < 500/mm³
  • Blast count < 20%
  • Chronic myelomonocytic leukemia (CMMoL; dysplastic subtype)
  • White blood cells (WBC) < 12,000/mm³ (measured twice within the past 4 weeks, 2 weeks apart)
  • Acute myeloid leukemia with multilineage dysplasia (AML-TLD)
  • Formerly diagnosed refractory anemia with excess blasts in transformation by French-American-British (FAB) criteria allowed
  • AML-TLD by World Health Organization (WHO) criteria allowed in patients with no history of antecedent hematologic disorder
  • WBC ≤ 30,000/mm³ (measured twice within the past 4 weeks, 2 weeks apart)
  • WBC that has doubled over 4 weeks and > 20,000/mm³ is not eligible
  • Evidence of ≥ 20% blasts on review of the bone marrow aspirate and/or biopsy
  • Therapy-induced MDS, AML-TLD, or chronic myelomonocytic leukemia (dysplastic subtype) allowed
  • Age ≥ 18 years.
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • ECOG performance status 0-2
  • Creatinine < 2.0 mg/dL
  • Bilirubin normal (unless due to intramedullary or extramedullary hemolysis, or Gilbert's syndrome)
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 times upper limit of normal
  • Life expectancy ≥ 6 months
  • SWOG (Southwest Oncology Group) patients must be enrolled in research study trial SWOG-9007

Exclusion Criteria:

  • Pregnant or nursing
  • Prior treatment with azacitidine, decitabine or entinostat
  • Active infections
  • Prior induction chemotherapy for AML or stem cell transplantation
  • Clinical evidence of central nervous system (CNS) or pulmonary leukostasis or disseminated intravascular coagulation or CNS leukemia
  • Serious or uncontrolled medical conditions
  • Advanced malignant hepatic tumors
  • Known hypersensitivity to azacitidine or mannitol

Trial Contact Information

Trial Lead Organizations/Sponsors

National Cancer Institute

Steven Gore, M.D.Study Chair

Link to the current ClinicalTrials.gov record.
NLM Identifer NCT00313586
ClinicalTrials.gov processed this data on November 24, 2014

Note: Information about this trial is from the ClinicalTrials.gov database. The versions designated for health professionals and patients contain the same text. Minor changes may be made to the ClinicalTrials.gov record to standardize the names of study sponsors, sites, and contacts. Cancer.gov only lists sites that are recruiting patients for active trials, whereas ClinicalTrials.gov lists all sites for all trials. Questions and comments regarding the presented information should be directed to ClinicalTrials.gov.

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