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

Overview

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.

Full Title of Study: “First Line Therapy With Methotrexate (MTX) and Second Line Therapy With Fludarabine of Patients With T-Cell Large Granular Lymphocyte Leukemia (T-LGL)”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: N/A
    • Intervention Model: Single Group Assignment
    • Primary Purpose: Treatment
    • Masking: None (Open Label)
  • Study Primary Completion Date: December 2009

Detailed Description

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.

Interventions

  • Drug: MTX followed by fludarabine
    • 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

Arms, Groups and Cohorts

  • Experimental: MTX followed by fludarabine
    • 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

Clinical Trial Outcome Measures

Primary Measures

  • Response rate
    • Time Frame: 12 months after inclusion in the study
    • 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

Secondary Measures

  • Duration of remission
    • Time Frame: up to 24 months after inclusion in the study
    • 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
  • Molecular remission rate
    • Time Frame: 2 months after the last dose of study medication
  • Adverse events rate and severity
    • Time Frame: up to 28 days after the last dose of study medication
    • Adverse events were reported according to the National Cancer Institute Common Toxicity Criteria (NCI-CTC version 2.0)

Participating in This Clinical Trial

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

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • German CLL Study Group
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Michael Kneba, Study Chair, University Hospital Schleswig-Holstein

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