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

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

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.

Study Overview

• Status: Terminated
• Conditions: T-Cell Large Granular Lymphocytic Leukemia
• Intervention / Treatment: Drug: MTX followed by fludarabine

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.

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 2

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany, D-13125
    • Robert Roessle Comprehensive Cancer Center - Charite Campus Buch
  • Kiel, Germany, D-24105
    • University Hospital Schleswig-Holstein - Kiel Campus
  • Munich, Germany, D-80337
    • I. Frauenklinik und Hebammenschule der Ludwig-Maximillians Universitaet Muenchen
  • Mutlangen, Germany, D-73557
    • Klinikum Schwaebisch Gmuend Stauferklinik
  • Norderstedt, Germany, 22844
    • Praxis fuer Haematologie und Interne Onkologie
  • Siegen, Germany, D-57072
    • St. Marien - Krankenhaus Siegen GMBH
  • Ulm, Germany, D-89081
    • Comprehensive Cancer Center Ulm at Universitaetsklinikum Ulm

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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	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; Other Names: methotrexate, fludarabine phosphate

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: German CLL Study Group
• Investigators: Study Chair: Michael Kneba, University Hospital Schleswig-Holstein

Publications and helpful links

Helpful Links

• Click here for more information about this study: LGL1 (German CLL Study Group)

Study record dates

Study Major Dates

• Study Start: June 1, 2005
• Primary Completion (Actual): December 1, 2009
• Study Completion (Actual): December 1, 2009

Study Registration Dates

• First Submitted: January 16, 2006
• First Submitted That Met QC Criteria: January 16, 2006
• First Posted (Estimate): January 18, 2006

Study Record Updates

• Last Update Posted (Estimate): October 3, 2016
• Last Update Submitted That Met QC Criteria: September 30, 2016
• Last Verified: September 1, 2016

More Information

Terms related to this study

• Keywords: anemia; neutropenia; T-cell large granular lymphocyte leukemia
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Leukemia, T-Cell; Leukemia; Leukemia, Lymphoid; Leukemia, Large Granular Lymphocytic; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antirheumatic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Dermatologic Agents; Reproductive Control Agents; Abortifacient Agents, Nonsteroidal; Abortifacient Agents; Folic Acid Antagonists; Fludarabine; Fludarabine phosphate; Methotrexate
• Other Study ID Numbers: LGL1; GCLLSG-LGL1; EU-20564; CDR0000454596 (Other Identifier: Clinical Data Repository)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No