OBJECTIVES:

Primary

• Determine the complete response rate in older patients with previously untreated poor-risk acute myeloid leukemia treated with tipifarnib.

Secondary

• Determine the progression-free and overall survival of patients treated with this drug.
• Determine the duration of response in patients treated with this drug.
• Determine the effect of this drug on the phosphorylation of mitogen-activated protein kinase (MAPK) and phosphatidyl inositol 3 kinase (PI3K) in leukemic cells in these patients.
• Determine the toxic effects of this drug in these patients.

OUTLINE: This is a multicenter study.

Patients receive oral tipifarnib twice daily on days 1-21. Patients with a complete or partial response, hematologic improvement, or stable disease continue treatment every 29-63 days in the absence of disease progression or unacceptable toxicity. Patients with a complete response after the second course of therapy receive 2 additional courses of therapy.

Patients are followed for survival.

PROJECTED ACCRUAL: A total of 125 patients will be accrued for this study within 11-17 months.

DISEASE CHARACTERISTICS:

• Histologically confirmed newly diagnosed acute myeloid leukemia (AML)

  • At least 20% blasts in bone marrow
• AML arising from myelodysplastic syndromes (MDS)
• No acute promyelocytic leukemia (M3)
• No hyperleukocytosis (at least 30,000 leukemic blasts/mm^3)
• No active CNS leukemia
• Ineligible for curative allogeneic stem cell transplantation

PATIENT CHARACTERISTICS:

Age:

• 65 and over

Performance status:

• ECOG 0-2

Life expectancy:

• Not specified

Hematopoietic:

• No disseminated intravascular coagulation (laboratory or clinical)

Hepatic:

• Bilirubin normal
• SGOT and SGPT no greater than 2.5 times normal

Renal:

• Creatinine no greater than 1.5 times normal

Cardiovascular:

• No severe congestive heart failure
• No unstable angina

Other:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No active systemic infection
• No known allergy to imidazole drugs (e.g., ketoconazole, miconazole, econazole, terconazole, clotrimazole, fenticonazole, isoconazole, sulconazole, or tioconazole))
• No physical or psychiatric condition that would preclude study compliance
• No poorly controlled psychosis
• No symptomatic neuropathy grade 2 or greater

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• See Disease Characteristics
• No concurrent immunotherapy

Chemotherapy:

• No prior chemotherapy for leukemia except hydroxyurea
• No concurrent chemotherapy

Endocrine therapy:

• Not specified

Radiotherapy:

• No concurrent radiotherapy

Surgery:

• Not specified

Other:

• At least 1 month since prior therapy for another malignancy