Decitabine and FR901228 in Treating Patients With Relapsed or Refractory Leukemia, Myelodysplastic Syndromes, or Myeloproliferative Disorders

DISEASE CHARACTERISTICS:

• Histologically confirmed diagnosis of 1 of the following hematologic malignancies:

  • Acute myeloid leukemia

    • Previously untreated patients > 60 years of age who are not eligible for front-line therapy are eligible for this study
  • Acute lymphoblastic leukemia

  • Chronic myelogenous leukemia (CML)

    • Documented hematologic resistance to imatinib mesylate OR no cytogenetic response after 12 months of prior treatment with imatinib mesylate
    • Philadelphia chromosome-negative CML allowed provided disease is resistant to standard therapy (e.g., hydroxyurea) OR disease progressed (blasts > 5% and platelet count < 100,000/mm^3) during standard therapy

  • Myelodysplastic syndromes

    • International Prognostic Scoring System risk category ≥ intermediate-1
    • Patients who are not eligible for front-line therapy are eligible for this study
  • Myeloproliferative disease

  • Chronic lymphocytic leukemia

    • Failed or progressed during ≥ 1 prior fludarabine-based therapy AND alemtuzmab

  • Acute promyelocytic leukemia

    • Progressed after prior treatment with standard chemotherapy, tretinoin, and arsenic trioxide

  • Chronic myelomonocytic leukemia

    • Resistant to standard therapy (e.g., hydroxyurea) OR disease progressed (blasts > 5% and platelet count < 100,000/mm^3) during standard therapy
• Relapsed or refractory disease
• No known brain or meningeal disease

PATIENT CHARACTERISTICS:

Age

• Over 18

Performance status

• ECOG 0-1

Life expectancy

• More than 8 weeks

Hepatic

• Bilirubin < 2 mg/dL
• AST and ALT ≤ 2.5 times upper limit of normal

Renal

• Creatinine < 2 mg/dL

Cardiovascular

• QTc < 500 msec
• LVEF > 40% by MUGA
• No New York Heart Association class III or IV congestive heart failure
• No myocardial infarction within the past year
• No uncontrolled dysrhythmias
• No uncontrolled angina
• No left ventricular hypertrophy by EKG
• No history of serious ventricular arrhythmia (e.g., ventricular tachycardia or ventricular fibrillation ≥ 3 beats in a row)
• No other significant cardiac disease

Immunologic

• No history of allergic reaction attributed to compounds of similar chemical or biologic composition to study drugs
• No ongoing or active infection
• No HIV positivity

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No psychiatric illness or social situation that would preclude study compliance
• No other uncontrolled illness

PRIOR CONCURRENT THERAPY:

Chemotherapy

• Recovered from prior chemotherapy
• At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) unless there is evidence of rapidly progressive disease

Radiotherapy

• At least 4 weeks since prior radiotherapy and recovered

Other

• No concurrent agents that cause QTc prolongation
• No other concurrent investigational or commercial agents or therapies for the malignancy

• No concurrent hydrochlorothiazide

  • Concurrent potassium-conserving combinations (e.g., Maxide® or Dyazide®) or other antihypertensive agents allowed