Tipifarnib in Treating Patients With Anemia or Neutropenia and Large Granular Lymphocyte Leukemia

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