Methotrexate Followed by Fludarabine in Patients With T-Cell Large Granular Lymphocytic Leukemia

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy, such as methotrexate and fludarabine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. PURPOSE: This phase II trial is studying how well methotrexate works as first-line therapy and fludarabine works as second-line therapy in treating patients with T-cell large granular lymphocytic leukemia.

Detailed Description
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OBJECTIVES: Primary Determine remission rates and duration of remission in patients with T-cell large granular lymphocytic (T-LGL) leukemia needing intervention because of anemia or neutropenia and are treated with parenteral methotrexate (MTX) as first-line therapy Determine remission rate and duration of remission in patients who fail to respond to MTX therapy and are subsequently treated with fludarabine as second-line therapy. Secondary Determine the side effects of these drugs in these patients. Determine the rate of molecular remissions in patients treated with these drugs. OUTLINE: This is a nonrandomized, open-label, multicenter study. Patients receive methotrexate subcutaneously once weekly in the absence of disease progression or unacceptable toxicity. Patients not achieving a response to methotrexate receive fludarabine IV on days 1-3. Treatment with fludarabine repeats every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity. PROJECTED ACCRUAL: A total of 30 patients will be accrued for this study.

Official Title
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First Line Therapy With Methotrexate (MTX) and Second Line Therapy With Fludarabine of Patients With T-Cell Large Granular Lymphocyte Leukemia (T-LGL)

Conditions
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T-Cell Large Granular Lymphocytic Leukemia

Intervention / Treatment
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* Drug: MTX followed by fludarabine


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Confirmed diagnosis of T-cell large granular lymphocytic (T-LGL) leukemia Must have concurrent anemia or neutropenia PATIENT CHARACTERISTICS: Life expectancy ≥ 2 years Not pregnant Fertile patients must use effective contraception No other malignancy No active infection PRIOR CONCURRENT THERAPY: No prior immunosuppressive treatment No previous treatment with methotrexate or fludarabine

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MTX followed by fludarabine<br>MTX is given with a dose of 10-20mg weekly Fludarabine is dosed with 25mg/m2 day 1-3 of 28 days, up to 4 cycles | Drug: MTX followed by fludarabine<br>* MTX should be administered with 10-20mg weekly, calculated according to the body weight. Fludarabine should be administered with 25mg/m2 on day 1-3 of 28 days, up to 4 cycles<br>* Other names: methotrexate, fludarabine phosphate;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response rate | he remission status was assessed according to the guidelines of the National Cancer Institute Sponsored Working Group (NCI-WG) [20 Cheson BD, Bennett JM, Grever M, et al. National Cancer Institute-sponsored Working Group guidelines for chronic lymphocytic leukemia: revised guidelines for diagnosis and treatment. Blood 1996; 87: 4990-4997.]. Restaging after the end of treatment included evaluation of the peripheral blood and physical examination; use of imaging techniques (ultrasound and conventional radiography or computertomography) and evaluation of the bone marrow were mandatory to assign a complete remission | 12 months after inclusion in the study | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of remission | he remission status was assessed according to the guidelines of the National Cancer Institute Sponsored Working Group (NCI-WG) [20 Cheson BD, Bennett JM, Grever M, et al. National Cancer Institute-sponsored Working Group guidelines for chronic lymphocytic leukemia: revised guidelines for diagnosis and treatment. Blood 1996; 87: 4990-4997.]. Restaging after the end of treatment included evaluation of the peripheral blood and physical examination; use of imaging techniques (ultrasound and conventional radiography or computertomography) and evaluation of the bone marrow were mandatory to assign a complete remission | up to 24 months after inclusion in the study | 
| Molecular remission rate |  | 2 months after the last dose of study medication | 
| Adverse events rate and severity | Adverse events were reported according to the National Cancer Institute Common Toxicity Criteria (NCI-CTC version 2.0) | up to 28 days after the last dose of study medication | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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T-cell large granular lymphocyte leukemia, anemia, neutropenia