Belinostat and Azacitidine in Treating Patients With Advanced Hematologic Cancers or Other Diseases

Inclusion Criteria:

• Histologically confirmed diagnosis of 1 of the following:

  • Relapsed or refractory acute myeloid leukemia (AML)
  • Relapsed or refractory acute promyelocytic leukemia (must have failed both tretinoin and arsenic trioxide)
  • Relapsed or refractory acute lymphoblastic leukemia
  • Secondary AML, including AML arising from antecedent hematologic diseases, such as myelodysplastic syndromes (MDS) or myeloproliferative disorders, OR therapy-related AML
  • Chronic myelogenous leukemia in accelerated or blast phase

  • Advanced phases of Philadelphia chromosome-negative (Ph-) chronic myeloproliferative disorders, as defined by ≥ 1 of the following:

    • Presence of anemia (hemoglobin < 10 g/dL and/or red blood cell transfusion dependent)
    • Presence of palpable splenomegaly

  • MDS, including chronic myelomonocytic leukemia

    • Must have intermediate or high-risk International Prognostic Scoring System (IPSS) scores (≥ 0.5)

    • Low-risk IPSS scores allowed provided ≥ 1 of the following criteria are met:

      • Hemoglobin < 10 g/dL and/or red blood cell transfusion dependent
      • Platelet count < 50,000/mm³
      • Absolute neutrophil count < 1,000/mm³
• Refractory disease OR no standard therapy exists
• Evidence of AML associated with dysplasia on bone marrow histology for elderly patients (i.e., > 60 years old) who are previously untreated and not candidates for or unwilling to undergoing induction therapy
• No known active CNS involvement with disease
• CALGB performance status (PS) 0-2 OR Karnofsky PS 60-100%
• Bilirubin ≤ 2.0 mg/dL (unless due to Gilbert's syndrome)
• ALT ≤ 3 times upper limit of normal (unless due to disease)
• Creatinine ≤ 2 mg/dL
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No history of allergic reactions attributed to compounds of similar chemical or biologic composition to PXD101 or Azacitidine
• No history of allergic reactions to mannitol
• No history of dose-limiting toxicity during prior treatment with Azacitidine

• No concurrent uncontrolled illness including, but not limited to, the following:

  • Ongoing or active infection
  • Symptomatic congestive heart failure
  • Unstable angina pectoris
  • Cardiac arrhythmia
  • Psychiatric illness or social situation that would preclude compliance with study requirements
• No marked baseline prolongation of QT/QTc interval (e.g., repeated demonstration of a QTc interval > 500 msec)
• No long QT syndrome

• No uncontrolled cardiovascular disease, including the following:

  • Severe uncontrolled hypertension
  • Uncontrolled congestive heart failure related to primary cardiac disease
  • Uncontrolled cardiac arrhythmia
  • Uncontrolled ischemic or severe valvular heart disease
  • Myocardial infarction within the past 6 months
• See Disease Characteristics
• Recovered from prior therapy
• At least 2 weeks since prior chemotherapy (6 weeks for mitomycin C or nitrosoureas)
• At least 2 weeks since prior radiotherapy
• At least 4 weeks since prior investigational agents
• At least 24 hours since prior hydroxyurea
• At least 2 weeks since prior valproic acid
• No concurrent combination antiretroviral therapy for HIV-positive patients
• No other concurrent investigational agents
• No concurrent medication that may cause torsade de pointes
• No other concurrent anticancer therapy, including chemotherapy, radiotherapy, or biological agents