Dasatinib and Vorinostat in Treating Patients With Accelerated Phase or Blastic Phase Chronic Myelogenous Leukemia or Acute Lymphoblastic Leukemia

DISEASE CHARACTERISTICS:

• Diagnosis of 1 of the following hematologic malignancies:

  • Chronic myelogenous leukemia meeting 1 of the following criteria:

    • In accelerated phase, defined by the presence of ≥ 1 of the following:

      • At least 15% but < 30% blasts in peripheral blood and/or bone marrow
      • At least 30% blasts plus promyelocytes in peripheral blood or bone marrow (providing that < 30% blasts are present in bone marrow)
      • At least 20% basophils in peripheral blood
      • Platelet count < 100,000/mm³ (unrelated to therapy) OR platelet count > 100,000/mm³ and unresponsive to therapy
      • Cytogenetic evidence of clonal evolution
      • Increasing spleen size and increasing WBC count and unresponsive to therapy

    • In blastic phase (blast crisis), defined by the presence of ≥ 1 of the following:

      • At least 30% blasts in peripheral blood and/or bone marrow
      • Extramedullary infiltrates of leukemic cells (other than liver or spleen involvement)

  • Philadelphia chromosome-positive acute lymphoblastic leukemia meeting any of the following criteria:

    • Newly diagnosed or relapsed disease
    • Previously treated with chemotherapy, stem cell transplantation, or tyrosine kinase inhibitors (TKIs)
• No active CNS involvement

PATIENT CHARACTERISTICS:

• ECOG performance status 0-2
• Total bilirubin < 2.0 times upper limit of normal (ULN)
• AST and ALT ≤ 2.5 times ULN
• Serum sodium, potassium, magnesium, phosphate, and calcium ≥ lower limit of normal
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for ≥ 4 weeks after discontinuation of study drug
• Able to take oral medication
• No active post-transplantation-related infections (e.g., fungal or viral infection)
• No active acute graft-versus-host disease (GVHD) of any grade
• No chronic GVHD (other than mild skin, oral, or ocular GVHD not requiring systemic immunosuppression)
• No other malignancy that required radiotherapy or systemic treatment within the past 5 years
• No concurrent medical condition that may increase the risk of toxicity, including pleural or pericardial effusion of any grade

• No cardiac conditions, including any of the following:

  • Uncontrolled angina, congestive heart failure, or myocardial infarction within the past 6 months
  • Diagnosed congenital long QT syndrome
  • History of clinically significant ventricular arrhythmias (e.g., ventricular tachycardia, ventricular fibrillation, or Torsades de pointes)
  • Prolonged QTc interval (i.e., QTc > 450 msec) on baseline EKG
• No hypokalemia or hypomagnesemia that cannot be corrected prior to dasatinib administration

• No history of significant bleeding disorder unrelated to cancer, including any of the following:

  • Diagnosed congenital bleeding disorder (e.g., von Willebrand's disease)
  • Acquired bleeding disorder diagnosed within the past year (e.g., acquired anti-factor VIII antibodies)
  • Ongoing or recent (i.e., within the past 3 months) significant gastrointestinal bleeding
• No prisoners or individuals who are compulsorily detained (i.e., involuntarily incarcerated) for treatment of either a psychiatric or physical (e.g., infectious) illness

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• Recovered from prior therapy

• No prior HDAC inhibitors or compounds with HDAC inhibitor-like activity (e.g., valproic acid) as anti-tumor therapy

  • Prior valproic acid for the treatment of seizures allowed provided it was not given within the past 30 days
• Prior allogeneic stem cell transplantation allowed
• More than 4 weeks since prior chemotherapy other than TKI (6 weeks for nitrosoureas and mitomycin)
• More than 2 weeks since prior radiotherapy

• At least 7 days since prior and no concurrent Category I drugs that are generally accepted to have a risk of causing Torsades de pointes, including any of the following:

  • Quinidine, procainamide, or disopyramide
  • Amiodarone, sotalol, ibutilide, or dofetilide
  • Erythromycin or clarithromycin
  • Chlorpromazine, haloperidol, mesoridazine, thioridazine, or pimozide
  • Cisapride, bepridil, droperidol, methadone, arsenic, chloroquine, domperidone, halofantrine, levomethadyl, pentamidine, sparfloxacin, or lidoflazine

• At least 7 days since prior and no concurrent medications that directly and durably inhibit platelet function, including any of the following:

  • Aspirin or aspirin-containing combinations, clopidogrel, or dipyridamole
  • Tirofiban, epoprostenol, eptifibatide, cilostazol, abciximab, ticlopidine, or cilostazol
• At least 5 days since prior and no concurrent St. John's wort
• No IV bisphosphonates during the first 8 weeks of dasatinib therapy