Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

Methotrexate With or Without Cyclophosphamide in Treating Patients With Lymphocytic Leukemia

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II	Treatment	Closed	18 and over	NCI	ECOG-5998 E5998, NCT00003910

Objectives

1. Determine the complete, partial, and overall response rates to methotrexate in patients with large granular lymphocytic (LGL) leukemia presenting with neutropenia or anemia.
2. Determine the complete, partial, and overall response rates to cyclophosphamide in the patients who fail to respond to methotrexate.
3. Assess the association of clinical response with increased sensitivity of leukemic LGL to Fas-dependent apoptosis, reduction in levels of Fas ligand, and disappearance of leukemic clone.
4. Determine the toxic effects of methotrexate and cyclophosphamide in these patients.

Entry Criteria

Disease Characteristics:

• Cytologically proven T-cell large granular lymphocytic (LGL) leukemia
  • Absolute LGL count greater than 500/mm3 (peripheral blood only)
  • CD3+ and CD57+ cells greater than 400/mm3

    OR

  • CD8+ cells greater than 650/mm3
  • Clonal T-cell receptor gene rearrangement
  • At least 1 of the following:
    • Severe neutropenia (neutrophil count less than 500/mm3)
    • Neutropenia associated with recurrent infections
    • Symptomatic anemia
    • Transfusion dependent anemia

Prior/Concurrent Therapy:

• No prior oral methotrexate or cyclophosphamide

Patient Characteristics:

Age:

• 18 and over

Performance status:

• ECOG 0-2

Life expectancy:

• At least 2 years

Hematopoietic:

• See Disease Characteristics

Hepatic:

• Bilirubin no greater than 2.0 mg/dL
• SGOT no greater than 1.5 times normal

Renal:

• Creatinine no greater than 2.0 mg/dL

Other:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No prior or concurrent malignancy within past 5 years except inactive nonmelanomatous skin cancer or carcinoma in situ of the cervix
• No other serious medical illness
• No concurrent psychiatric condition

Expected Enrollment

A total of 38-88 patients will be accrued for this study.

Outcomes

Complete, partial, and overall response rates
Clinical response
Toxic effects

Outline

Patients are stratified according to symptom (neutropenia vs anemia).

Patients receive oral methotrexate once a week for 4 months and oral prednisone daily for 54 days. Patients who show a partial response to methotrexate may continue this therapy for up to 1 year. Patients who do not respond to this therapy after 4 months then receive oral cyclophosphamide daily for up to 1 year and oral prednisone daily for 54 days.

Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

Trial Contact Information

Trial Lead Organizations

Eastern Cooperative Oncology Group

Thomas Loughran, MD, Protocol chair		Ph: 717-531-4034 Email: tloughran@psu.edu

Registry Information
Official Title		A Phase II Study of Initial Treatment with Methotrexate in Large Granular Lymphocytic (LGL) Leukemia
Trial Start Date		1999-07-16
Trial Completion Date		2001-05-06 (estimated)
Registered in ClinicalTrials.gov		NCT00003910
Date Submitted to PDQ		1999-05-26
Information Last Verified		2009-03-24
NCI Grant/Contract Number		U10-CA21115

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