Tipifarnib in Treating Older Patients With Previously Untreated Acute Myeloid Leukemia

PRIMARY OBJECTIVES:

I. To determine the complete response rate of R115777 (tipifarnib) in previously untreated acute myeloid leukemia (AML) in (a) elderly patients (age >= 75) and (b) patients (age >= 65) with AML preceded by myelodysplastic syndrome (MDS), using a chronic dosing schedule.

SECONDARY OBJECTIVES:

I. To determine progression-free and overall survival in patients with previously untreated AML treated with R115777, using a chronic dosing schedule.

II. To determine the duration of response in patients with previously untreated AML treated with R115777, using a chronic dosing schedule.

III. To determine the effect of R115777 on the phosphorylation of mitogen-activated protein kinase (MAPK) and phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PI3K) in leukemic cells.

IV. To determine the effect of R115777 on processing of the farnesylated protein HDJ-2.

V. To determine the toxicities of R115777 when given in a chronic dosing schedule.

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.

Inclusion criteria

• Pathologic confirmation of the diagnosis of AML (>= 20% marrow blasts)
• ECOG performance status 0 or 1
• Patients must be able to give informed consent
• SGOT and SGPT =< 2.5 x normal limits (grade 1)
• Serum creatinine =< 1.5 x normal limits (grade 1)
• AML (any of the following):

• Newly diagnosed AML in adults >= 75 years
• Newly diagnosed AML arising from MDS in adults >= 65 years
• Hyperleukocytosis with >= 30,000 leukemic blasts/uL

Exclusion criteria

• Acute promyelocytic (FAB M3) subtype
• Previously treated with chemotherapy for leukemia (except for hydroxyurea)
• Disseminated intravascular coagulation (laboratory or clinical)
• Active central nervous system leukemia
• Concomitant radiation therapy, chemotherapy, or immunotherapy; previous therapy for another malignancy is permitted, provided that at least 1 month has occurred since patient received any of these treatments
• Intrinsic impaired organ function (as stated above)
• Symptomatic neuropathy (grade 2 or worse)
• Known allergy to imidazole drugs, such as ketoconazole, miconazole, econazole, teconazole, clotrimazole, fenticonazole, isoconazole, sulconazole, or ticonazole
• Physical or psychiatric conditions that in the estimation of the principal investigator (PI) or designee place the patient at high risk of toxicity or non-compliance, e.g. severe congestive heart failure (CHF), unstable angina, or poorly controlled psychosis