Tipifarnib may stop the growth of cancer cells by blocking the enzymes necessary for their
growth. Phase II trial to study the effectiveness of tipifarnib in treating older patients
who have previously untreated acute myeloid leukemia
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.
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
Patients are followed for survival.
PROJECTED ACCRUAL: A total of 125 patients will be accrued for this study within 11-17
- 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
- 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