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:

- Age ≥ 65 with previously untreated AML (de novo or secondary)

- Deemed unsuitable for or refuses standard induction chemotherapy

- RASGRP1:APTX ratio ≥5, through bone marrow screening

- Eastern Cooperative Oncology Group (ECOG) performance status ≤2

- Patients must have normal organ function as defined below:

- 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 (CTC Grade 1), unless the increase is
unequivocally due to hemolysis or Gilbert's Syndrome

- Alanine transaminase (ALT) and aspartate transaminase (AST) less than 2.5 times ULN
(CTC Grade 1)

- Ability to understand and the willingness to sign a written informed consent document

- The effects of R115777 (ZARNESTRA) on the developing human fetus are unknown. For
this reason and because farnesyl transferase inhibitor (FTI) agents as well as other
therapeutic agents used in this trial are known to be teratogenic, 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.

Exclusion Criteria:

- Diagnosis of acute promyelocytic leukemia (APL)

- Patients who are receiving any other investigational agents

- Patients with known leukemic involvement of the central nervous system

- Patients with white blood cells (WBC) ≥ 30,000/uL (hydroxyurea permitted up to 24
hours prior to initiation of therapy)

- Symptomatic neuropathy of grade 2 or worse

- Uncompensated disseminated intravascular coagulation (DIC) or uncontrolled bleeding

- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to R115777, such as the imidazole drugs, including clotrimazole,
ketoconazole, miconazole, econazole, fenticonazole, isoconazole, sulconazole,
tioconazole or terconazole

- Use of enzyme-inducing anticonvulsants (e.g., phenytoin, fosphenytoin, phenobarbital,
primidone, carbamazepine, oxcarbazepine) while taking R115777 is contraindicated. If
clinically indicated, subjects may use nonenzyme-inducing anticonvulsants during
treatment with R115777.

- 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 human immunodeficiency virus (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/mm³ are
eligible.