Phase 2 Trial of R115777 in Previously Untreated Older Adults With AML and Baseline Presence of a Specific 2-Gene Expression Signature Ratio

Inclusion Criteria:

- Previously untreated acute myeloid leukemia (AML) (de novo or secondary)

- No diagnosis of acute promyelocytic leukemia (APL)

- Deemed unsuitable for or refuses standard induction chemotherapy

- RASGRP1:APTX ratio >= 5, through bone marrow screening

- No patients with known leukemic involvement of the central nervous system

- ECOG performance status =< 2

- No WBC >= 30,000/uL (hydroxyurea permitted up to 24 hours prior to initiation of
therapy)

- Serum creatinine less than 1.5 times the upper limit of the normal range (ULN)
(National Cancer Institute [NCI] Common Toxicity Criteria [CTC] Grade 1)

- Total bilirubin less than 1.5 times ULN (unless the increase is unequivocally due to
hemolysis or Gilbert syndrome)

- ALT and AST less than 2.5 times ULN (NCI CTC Grade 1)

- Men must agree to use adequate contraception (hormonal or barrier method of birth
control; abstinence) prior to study entry and for the duration of study participation

- No symptomatic neuropathy of grade 2 or worse

- No uncompensated disseminated intravascular coagulation (DIC) or uncontrolled
bleeding

- No history of allergic reactions attributed to compounds of similar chemical or
biologic composition to tipifarnib (R115777), such as the imidazole drugs, including
clotrimazole, ketoconazole, miconazole, econazole, fenticonazole, isoconazole,
sulconazole, ticonazole, or terconazole

- No uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit compliance with
study requirements

- Known HIV-positive patients on combination antiretroviral therapy are ineligible
because of the potential for pharmacokinetic interactions with R115777; in addition,
these patients are at increased risk of lethal infections when treated with
marrow-suppressive therapy; known HIV-positive patients NOT on antiretroviral therapy
AND with a CD4 cell count >= 400/mm^3 are eligible

- No other concurrent cytotoxic or biologic antileukemic therapy

- No patients who are receiving any other investigational agents

- Use of enzyme-inducing anticonvulsants (e.g., phenytoin, fosphenytoin, phenobarbital,
primidone, carbamazepine, oxcarbazepine) while taking tipifarnib (R115777) is
contraindicated

- If clinically indicated, subjects may use non-enzyme-inducing anticonvulsants
during treatment with R115777