• 6-month disease-free survival [ Designated as safety issue: No ]
  

• Tolerability and toxicity [ Designated as safety issue: Yes ]
  

OBJECTIVES:

• Determine the duration of disease-free survival and overall survival of patients with poor-risk acute myeloid leukemia or high-risk myelodysplastic syndromes in early first complete remission treated with tipifarnib.
• Determine the tolerability and toxic effects of this drug in these patients.

OUTLINE: This is a multicenter study.

Patients receive oral tipifarnib twice daily on days 1-14. Treatment repeats every 21 days for up to 16 courses in the absence of disease progression or unacceptable toxicity.

PROJECTED ACCRUAL: A total of 14-44 patients will be accrued for this study within 11-15 months.

DISEASE CHARACTERISTICS:

• Histologically confirmed diagnosis of 1 of the following:

  • Poor-risk acute myeloid leukemia (AML), defined as any of the following:

    • Antecedent hematologic disorder
    • AML arising from myelodysplastic syndromes (MDS)
    • Therapy-related AML
    • 60 years of age or over (in absence of favorable cytogenetics)
    • Adverse cytogenetics (e.g., -5/5q, -7/7q, 20q-, or 11q23 abnormalities or complex karyotype)
    • Hyperleukocytosis at diagnosis (e.g., blasts at least 50,000/mm^3 in absence of favorable cytogenetics)
    • No acute promyelocytic leukemia (FAB M3 subtype)

  • High-risk myelodysplastic syndromes (MDS), defined as any of the following:

    • Chronic myelomonocytic leukemia with more than 5% marrow blasts
    • Therapy-related MDS
    • Refractory anemia with excess blasts (RAEB) with IPSS score at least 1.5
    • RAEB in transformation with IPSS score at least 1.5

• In early first complete remission after completing induction and consolidation chemotherapy

  • No more than 21-35 days since hospital discharge after marrow recovery from consolidation therapy
  • No more than 120 days since initiation of the final course of consolidation therapy
• No presence of residual AML (more than 5% marrow blasts) or MDS by morphology, flow cytometry, and/or cytogenetics
• No active CNS leukemia
• No presence of (8;21) translocation or inversion 16 genotype as sole abnormality
• Ineligible for curative allogeneic stem cell transplantation

PATIENT CHARACTERISTICS:

Age

• See Disease Characteristics
• 18 and over

Performance status

• ECOG 0-2

Life expectancy

• Not specified

Hematopoietic

• Polymorphonuclear cell count at least 1,000/mm^3
• Platelet count at least 30,000/mm^3*
• Hemoglobin at least 9 g/dL*
• Hematocrit at least 27%* NOTE: *Unsupported

Hepatic

• Bilirubin no greater than 1.5 times normal
• AST and ALT no greater than 2.5 times normal
• Alkaline phosphatase no greater than 2.5 times normal

Renal

• Creatinine no greater than 2.0 mg/dL OR
• Creatinine clearance at least 40 mL/min

Cardiovascular

• No disseminated intravascular coagulation
• LVEF at least 25%

Other

• No active uncontrolled infection
• No known allergy to imidazole drugs (e.g., ketoconazole or miconazole)
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy

• No concurrent immunotherapy

Chemotherapy

• See Disease Characteristics
• No concurrent chemotherapy

Endocrine therapy

• Not specified

Radiotherapy

• No concurrent radiotherapy

Surgery

• Not specified

Other

• No prior tipifarnib
• No concurrent participation in another phase II or phase III study in which disease-free survival and overall survival are primary endpoints