Azacitidine With or Without Entinostat in Treating Patients With Myelodysplastic Syndromes, Chronic Myelomonocytic Leukemia, or Acute Myeloid Leukemia
Condition: 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
MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Preleukemia; Neoplasm Metastasis; Leukemia, Myelomonocytic, Acute; Leukemia, Myelomonocytic, Chronic; Leukemia, Myelomonocytic, Juvenile; Leukemia, Promyelocytic, Acute; Myelodysplastic Syndromes; Syndrome
Intervention: Azacitidine; Entinostat; Laboratory Biomarker Analysis
Intervention description: Given SC; Given PO; Correlative studies
Intervention MeSH terms: Azacitidine; Entinostat; Histone Deacetylase Inhibitors
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 197.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

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.
    

Eligibility criteria:

        Inclusion Criteria:

          -  The following diagnoses will be eligible for this study:

          -  Myelodysplastic syndromes: the diagnosis of MDS must be confirmed by a bone marrow
             aspirate and/or biopsy within two weeks prior to registration; NOTE: blast count must
             be < 20%; patients with any International Prognostic Score (IPSS) are eligible;
             patients with low or intermediate (INT)-1 IPSS must have a platelet count <
             50,000/mm^3 and/or absolute neutrophil count (ANC) < 500/mm^3 within seven days prior
             to registration

          -  Chronic myelomonocytic leukemia (dysplastic subtype): the diagnosis of CMMoL must be
             confirmed by a bone marrow aspirate and/or biopsy within two weeks prior to
             registration; patients with CMMoL must have a WBC < 12,000/mm^3, documented within 4
             weeks prior to study entry (two sets of counts that are 2 weeks apart will be taken)

          -  Acute myeloid leukemia with multilineage dysplasia: the diagnosis of AML-TLD must be
             confirmed by a bone marrow aspirate and/or biopsy within two weeks prior to
             registration; NOTE: there must be evidence of >= 20% blasts on the review of the bone
             marrow aspirate and/or biopsy; AML-TLD will be interpreted to include patients
             formerly diagnosed by French-American-British (FAB) criteria as refractory anemia with
             excess blasts in transformation (RAEB-t), as well as patients with no history of
             antecedent hematologic disorder who have AML which meets criteria for AML-TLD by World
             Health Organization (WHO) criteria; patients with AML-TLD must have a white blood cell
             (WBC) =< 30,000/mm^3 documented within 4 weeks prior to study entry (two sets of
             counts that are 2 weeks apart will be taken); patients whose WBC has doubled within
             this period of time and is greater than 20,000/mm^3 at the time of screening will not
             be eligible

          -  Women must not be pregnant or breast-feeding; all females of childbearing potential
             must have a blood test or urine study within two weeks prior to registration to rule
             out pregnancy

          -  Women of childbearing potential and sexually active males must be strongly advised to
             use an accepted and effective method of contraception

          -  Patient must have Eastern Cooperative Oncology Group (ECOG) performance status between
             0-2

          -  Patient must have no prior treatment with azacitidine, decitabine or entinostat

          -  Patients must not have active infections at the time of registration

          -  Serum creatinine < 2.0 mg/dL; test must be done within seven days prior to
             registration

          -  Total serum bilirubin within institutional limits unless due to intra- or
             extramedullary hemolysis or Gilbert's syndrome; test must be done within seven days
             prior to registration

          -  Aspartate transaminase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and
             alanine transaminase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x
             institutional upper limit of normal (ULN); tests must be done within seven days prior
             to registration

          -  Patients must not have received any AML induction chemotherapy or stem cell
             transplantation; any other treatment for their disease, including hematopoietic growth
             factors may not be given, within three weeks prior to registration, and should have
             recovered from all toxicities of prior therapy (to grade 0 or 1)

          -  Patients must have no clinical evidence of central nervous system (CNS) or pulmonary
             leukostasis, disseminated intravascular coagulation, or CNS leukemia

          -  Patients must have no serious or uncontrolled medical conditions

          -  Patients who have therapy-induced MDS, CMMoL (dysplastic) and AML-TLD are eligible and
             will be treated as separate cohorts from the patients with de novo MDS, CMMoL
             (dysplastic) and AML-TLD

          -  Patients should have a life expectancy of at least six months

          -  Patients must not have advanced malignant hepatic tumors

          -  Patients must not have a known hypersensitivity to azacitidine or mannitol

          -  Southwest Oncology Group (SWOG) ONLY: all SWOG patients must be registered on
             SWOG-9007 ("Cytogenetic Studies in Leukemia Patients"); collection of the pretreatment
             bone marrow specimen (or of peripheral blood if the marrow is not aspirable) must be
             completed within 28 days before registration; the pretreatment specimen must be
             submitted to a SWOG-approved cytogenetics laboratory as described in protocol
             SWOG-9007; note that submission of bone marrow cytogenetic studies are required to
             calculate the IPSS score (stratification issue); in addition, cytogenetic response
             will be measured at follow-up requiring a second cytogenetic study at the end of
             protocol treatment; NOTE: In addition to SWOG-9007, SWOG patients must be offered
             participation in S9910, the leukemia centralized reference laboratories and tissue
             repositories ancillary study; If consent is given, collection of pretreatment blood
             and/or marrow specimens must be completed within 14 days prior to registration. If the
             patient consents to participate in S9910, pretreatment specimens of marrow and/or
             peripheral blood must be submitted to the Southwest Oncology Group Myeloid Repository
             at the University of New Mexico for cellular and molecular studies; S9910 also
             requests submission of remission and relapse specimens