RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die.

PURPOSE: This phase I trial is studying the side effects and best dose of decitabine in treating patients with myelodysplastic syndromes or acute myeloid leukemia.

OBJECTIVES:

• Determine the maximum tolerated dose of decitabine in patients with high-risk myelodysplastic syndromes or acute myeloid leukemia.
• Determine the minimum effective dose of this drug that produces demethylation of DNA with tolerable toxicity in these patients.
• Determine the minimum effective dose of this drug that augments in vitro responses to retinoids.
• Determine the pharmacokinetics of this drug in these patients.
• Determine the clinical response rate of patients treated with this drug.

OUTLINE: This is a dose-escalation, multicenter study.

Patients receive decitabine IV over 3 hours twice daily OR IV over 1 hour once daily on days 1-5. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of decitabine 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.

PROJECTED ACCRUAL: A maximum of 36 patients will be accrued for this study within 18 months.

• Leukemia
• Myelodysplastic Syndromes
• Myelodysplastic/Myeloproliferative Diseases

DISEASE CHARACTERISTICS:

• One of the following diagnoses:

  • High-risk myelodysplastic syndromes (MDS)

  • Acute myeloid leukemia (AML)

    • De novo, secondary, or relapsed disease
    • Any number of prior regimens for primary or relapsed disease
• Ineligible for or refuses aggressive management

• Measurable disease, defined as:

  • More than 5% blasts in bone marrow of patients with MDS
  • More than 30% blasts in bone marrow of patients with AML
• Involvement of cerebrospinal fluid allowed

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• ECOG 0-2 OR
• Karnofsky 60-100%

Life expectancy

• Not specified

Hematopoietic

• See Disease Characteristics

Hepatic

• Bilirubin no greater than 1.25 times upper limit of normal (ULN)
• AST and/or ALT no greater than 1.25 times ULN

Renal

• Creatinine less than 1.7 mg/dL OR
• Creatinine clearance at least 60 mL/min

Cardiovascular

• No symptomatic congestive heart failure
• No unstable angina pectoris
• No cardiac arrhythmia

Other

• No ongoing or active infection
• No other uncontrolled illness that would preclude study participation
• No psychiatric illness or social situation that would preclude study compliance
• No prior allergic reactions to compounds of similar chemical or biological composition to decitabine
• No other active malignancy
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy

• At least 4 weeks since prior biologic therapy (e.g., interferon, filgrastim [G-CSF], sargramostim [GM-CSF], thrombopoietin, or epoetin alfa)
• No concurrent hematopoietic growth factors (GM-CSF, thrombopoietin, or epoetin alfa)
• No concurrent prophylactic G-CSF

Chemotherapy

• Prior intrathecal cytarabine allowed for patients with cerebrospinal fluid involvement
• At least 4 weeks since prior chemotherapy (except low-dose chemotherapy administered to maintain WBC counts) (6 weeks for nitrosoureas or mitomycin) and recovered
• At least 24 hours since prior hydroxyurea
• Concurrent intrathecal cytarabine allowed for patients with cerebrospinal fluid involvement

Endocrine therapy

• Not specified

Radiotherapy

• No prior radiotherapy greater than 3,000 cGy to marrow-producing areas
• At least 4 weeks since prior radiotherapy and recovered

Surgery

• Not specified

Other

• Prior investigational therapy allowed
• No other concurrent investigational agents
• No concurrent combination antiretroviral therapy for HIV-positive patients
• No other concurrent anticancer therapy