Zarnestra in Newly Diagnosed Acute Myelogenous Leukemia (AML)With 2 Gene Expression Signature Ratio

• Median Overall Survival (OS) Rate [ Time Frame: From first treatment through follow up period, an expected average of 12 months ] [ Designated as safety issue: No ]
  Overall survival is calculated from the first day of R115777 treatment and lasts until the date of death recorded on the case report form (CRF).
• Median 1-Year Survival Rate [ Time Frame: Up to 12 months per participant ] [ Designated as safety issue: No ]
  One year survival will be calculated from Kaplan Meier estimates.
• Number of Serious Adverse Events Reported That May be Related to Study Treatment [ Time Frame: From first treatment through follow up period, an expected average of 7 months ] [ Designated as safety issue: Yes ]
  All patients receiving R115777 will be evaluable for toxicity from the time of their first treatment with R115777, up through the 30-day follow up period after treatment termination, or until the initiation of subsequent therapy, whichever comes first.

• Median Overall Survival (OS) Rate [ Time Frame: From first treatment through follow up period, an expected average of 12 months ] [ Designated as safety issue: No ]
  Overall survival is calculated from the first day of R115777 treatment and lasts until the date of death recorded on the CRF.
• Median 1-Year Survival Rate [ Time Frame: Up to 12 months per participant ] [ Designated as safety issue: No ]
  One year survival will be calculated from Kaplan Meier estimates.
• Number of Serious Adverse Events Reported That May be Related to Study Treatment [ Time Frame: From first treatment through follow up period, an expected average of 7 months ] [ Designated as safety issue: Yes ]
  All patients receiving R115777 will be evaluable for toxicity from the time of their first treatment with R115777, up through the 30-day follow up period after treatment termination, or until the initiation of subsequent therapy, whichever comes first.

The purpose of this study is to determine the ability of a new test to predict whether patients will benefit from treatment with R115777 (ZARNESTRA, also called Tipifarnib). R115777 is an orally dosed, medication that inhibits the activity of the Farnesyl Transferase protein. Scientific experiments have suggested that R115777 can inhibit the function of proteins that play a role in the development of leukemia, and clinical studies of R115777 in humans has demonstrated that it can induce complete remissions (CR) in approximately 8-20% of patients with AML. R115777 is an investigational or experimental anticancer agent that has not yet been approved by the Food and Drug Administration for use in Acute Myelogenous Leukemia (AML).

This study will test the ability of a newly developed screening test, the RASGRP1:aprataxin (APTX) ratio, to identify patients who are more likely to benefit from R115777 therapy. RASGRP1 and APTX are genes that are expressed in leukemia cells. This test is performed on a sample of bone marrow tissue, and determines the ratio of RASGRP1 and APTX expression in the bone marrow. Ratios that are C5 are will be considered as a positive result, and these patients will be eligible for treatment with R115777. The ratio of C5 is expected to be found in about 30% of patients. This screening test is still considered an experimental procedure.

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.