This phase I trial is studying the side effects and best dose of decitabine and FR901228 in treating patients with relapsed or refractory leukemia, myelodysplastic syndromes or myeloproliferative disorders. Drugs used in chemotherapy, such as decitabine and FR901228, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. FR901228 may also stop the growth of cancer cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the cancer. Giving decitabine together with FR901228 may kill more cancer cells.

PRIMARY OBJECTIVES:

I. Determine the maximum tolerated dose and recommended phase II dose of decitabine and FR901228 (depsipeptide) in patients with relapsed or refractory leukemia, myelodysplastic syndromes, or myeloproliferative disease.

II. Determine the safety and tolerability of this regimen in these patients.

SECONDARY OBJECTIVES:

I. Determine the clinical activity of this regimen in these patients.

OUTLINE: This is a dose-escalation study.

Patients receive decitabine IV over 1 hour on days 1-5 and 8-12 and FR901228 (depsipeptide) IV over 4 hours on days 5 and 12 OR days 5, 12, and 19. Treatment repeats every 4-6 weeks for at least 2 courses in the absence of disease progression or unacceptable toxicity. Patients experiencing complete remission for 1 year are removed from the study.

Cohorts of 6 patients receive escalating doses of decitabine and FR901228 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity.

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