Zarnestra in Newly Diagnosed Acute Myelogenous Leukemia (AML)With 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.