Inclusion Criteria:

- Diagnosis of T-cell-large granular lymphocyte (LGL) leukemia or natural killer
(NK)-LGL leukemia associated with ≥ 1 of the following clinical manifestations:

- Severe neutropenia (i.e., < 500/mm³)

- Neutropenia associated with recurrent infections, meeting 1 of the following
criteria: one severe infection requiring hospitalization or at least 2
infections requiring antibiotic therapy

- Symptomatic anemia with significant fatigue with a score of greater than 1 on
the Eastern Cooperative Oncology Group (ECOG) Performance Status Scale; dyspnea
on exertion, but able to walk one flight of stairs without stopping (less than
grade 1 respiratory symptoms); cardiac symptoms including worsening of angina or
new onset of chest pain

- Transfusion-dependent anemia

- Willing to discontinue use of MTX, Cy, or cyclosporine for 1 month prior to study
entry

- T-cell-LGL leukemia must meet all of the following criteria: CD3+ and CD57+ cells >
300/mm³ or CD8+ cells > 650/mm³ by phenotypic studies of peripheral blood, evidence
for clonal T-cell receptor gene rearrangement based on positive flow cytometric
analysis, T-cell receptor (TCR)-γ chain polymerase chain reaction (PCR), TCR-Vβ PCR,
or by Southern blot analysis

- NK-LGL leukemia must have CD56+ or CD16+ NK cells > 750/mm³ by phenotypic studies of
peripheral blood

- Life expectancy > 2 years

- ECOG performance status (PS) 0-2 OR Karnofsky PS 60-100%

- Fertile patients must use effective contraception prior to and during study

- Negative pregnancy test

- Normal kidney and liver function, as determined by the following laboratory results:
total bilirubin less than or equal to 2.0 mg/dl; AST (SGOT) and ALT (SGPT) less than
or equal to 2.5 times the upper limit of normal; and creatinine less than or equal to
2.0 mg/dl

Exclusion Criteria:

- Not pregnant or nursing

- No history of allergic reactions attributed to compounds of similar chemical or
biologic composition to tipifarnib

- No allergies to imidazoles (e.g., clotrimazole, ketoconazole, miconazole, econazole,
fenticonazole, isoconazole, sulconazole, tioconazole, or terconazole)

- No uncontrolled concurrent illness including, but not limited to, any of the
following: ongoing or active infection, symptomatic congestive heart failure,
unstable angina pectoris, cardiac arrhythmia, psychiatric illness or social
situations that would limit study compliance

- No other serious medical illness that would limit survival to < 2 years

- No other malignancy within the past 5 years except inactive nonmelanoma skin cancer
or carcinoma in situ of the cervix

- Psychiatric illness that may interfere with study participation

- No other anticancer agents or therapies

- No concurrent antiretroviral therapy for HIV-positive patients

- No other concurrent investigational agents

- No prior tipifarnib or other inhibitors of MAPK signaling intermediates