• Clinical response to tipifarnib [ Time Frame: Measured at Months 4 and 8, and at follow-up evaluations performed twice a year for 5 years following treatment ] [ Designated as safety issue: Yes ]
  

• Sensitivity of leukemic LGL to Fas-dependent apoptosis [ Time Frame: Measured at Months 4 and 8, and at follow-up evaluations performed twice a year for 5 years following treatment ] [ Designated as safety issue: Yes ]
  
• Levels of activated Ras, ERK, and other proteins [ Time Frame: Measured at Months 4 and 8, and at follow-up evaluations performed twice a year for 5 years following treatment ] [ Designated as safety issue: Yes ]
  

LGL leukemia is a rare form of cancer that negatively affects either T lymphocyte cells (T-LGL leukemia) or natural killer cells (NK-LGL leukemia). Both cell types are examples of white blood cells that originate in the lymph system and bone marrow. T lymphocytes help fight infection and natural killer cells help attack tumors, both of which are important to the body's defense system. Individuals with LGL leukemia frequently suffer from low red blood cell levels (anemia) and low white blood cell levels (neutropenia). Anemic individuals often feel tired and fatigued because less oxygen is being carried in the blood. Neutropenia places the body at high risk for developing infections. Currently, individuals with LGL leukemia are usually treated with immunosuppressive drugs. However, no standard therapy has been established and some individuals do not respond well to these drugs. Tipifarnib (R115777), a drug that blocks enzymes needed for the activation of cancer-promoting proteins, holds potential for treating LGL leukemia. This study will examine the effects of tipifarnib in individuals diagnosed with T-LGL and NK-LGL leukemia who have anemia and/or neutropenia.

This study will enroll individuals with a diagnosis of T-LGL leukemia or NK-LGL leukemia. At an initial screening visit, participants will undergo a physical exam and an electrocardiogram. Medical histories will be reviewed and blood will be drawn for laboratory tests. A bone marrow sample will also be taken prior to treatment. Treatment will consist of a 28-day medication cycle in which participants will receive 300 mg of tipifarnib twice a day for 21 days, followed by no medication for 7 days. If the initial group of participants responds favorably to the medication, additional participants will be enrolled into the study and receive the same treatment dose. If the initial group of participants does not respond favorably, then additional participants enrolled into the study will receive 600 mg of tipifarnib. The same 28-day medication dosing schedule will follow.

Study visits will take place once a week. During the first 2 months, blood will be collected at each visit. Physical exams will occur on a monthly basis throughout the study. After four months of treatment, each participant's response to the medication will be evaluated. Participants who have responded well will continue in the study for 1 additional month; participants who have not responded well will continue in the study for 4 additional months. All participants will be asked to keep a daily log to record medication use. Follow-up evaluations will occur every 6 months for 5 years following the end of treatment. At each follow-up visit, participants will undergo a physical exam and blood collection.