A Phase 2 Study of R115777 in Large Granular Lymphocyte (LGL) Leukemia
18 Years
N/A
Both
Leukemia, Lymphocytic, Neutropenia, Anemia
Trial Information
A Phase 2 Study of R115777 in Large Granular Lymphocyte (LGL) Leukemia
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.
Inclusion Criteria:
- Diagnosis of T-LGL leukemia or NK-LGL leukemia that is associated with at least one
of the following four conditions:
1. severe neutropenia less than 500/mm³
2. neutropenia associated with recurrent infections, including one severe infection
requiring hospitalization or two or more infections requiring antibiotic therapy
3. 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
4. transfusion-dependent anemia
- Participants with T-LGL leukemia: CD3+ or CD57+ cells greater than 300/mm³, or CD8+
cells greater than 650/mm³; and evidence of clonal T-cell receptor gene rearrangement
- Participants with NK-LGL leukemia: CD56+ or CD16+ NK cells greater than 750/mm³
- 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
- Willing to discontinue use of MTX, Cy, or cyclosporine for 1 month prior to study
entry
- Life expectancy of greater than 2 years
- Score of 0, 1, or 2 on ECOG Performance Status Scale (equivalent to at least 60% on
the Karnofsky Performance Scale)
- Willing to use contraception throughout the study
Exclusion Criteria:
- Previous or concurrent tumors (inactive non-melanoma skin cancer, in situ carcinoma
of the cervix, or disease-free cancer of more than 5 years is acceptable)
- Serious medical illness, other than leukemia, that would limit survival to less than
2 years
- Uncontrolled concurrent illness, including ongoing or active infection, symptomatic
congestive heart failure, unstable angina pectoris, or cardiac arrhythmia
- Psychiatric illness that may interfere with study participation
- HIV-infected and receiving antiretroviral therapy (HIV-infected individuals who are
not receiving retroviral therapy may participate)
- Receiving any other investigational study drugs
- Previously treated with tipifarnib or other inhibitors of MAPK signaling
intermediates
- History of allergic reaction to imidazoles, including clotrimazole, ketoconazole,
miconazole, econazole, fenticonazole, isoconazole, sulconazole, tioconazole, or
terconazole
- Pregnant or breastfeeding
Type of Study:
Interventional
Study Design:
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Clinical response to tipifarnib
Outcome Time Frame:
Measured at Months 4 and 8, and at follow-up evaluations performed twice a year for 5 years following treatment
Safety Issue:
Yes
Principal Investigator
Thomas P. Loughran, Jr., MD
Investigator Role:
Principal Investigator
Investigator Affiliation:
Penn State University
Authority:
United States: Food and Drug Administration
Study ID:
RDCRN 5402
NCT ID:
NCT00331591
Start Date:
May 2006
Completion Date:
May 2007
Related Keywords:
- Leukemia, Lymphocytic
- Neutropenia
- Anemia
- Large Granular Lymphocytic Leukemia
- Anemia
- Leukemia
- Leukemia, Lymphoid
- Neutropenia
- Leukemia, Large Granular Lymphocytic
Name | Location |
|---|---|
| H. Lee Moffitt Cancer Center | Tampa, Florida 33612 |
| The Cleveland Clinic Foundation | Cleveland, Ohio |
| Pennsylvania State University | Hershey, Pennsylvania 17033 |
