Methotrexate With or Without Cyclophosphamide in Treating Patients With Lymphocytic Leukemia
RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die.
PURPOSE: Phase II trial to study the effectiveness of methotrexate with or without cyclophosphamide in treating patients who have lymphocytic leukemia with neutropenia or anemia.
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase II Study of Initial Treatment With Methotrexate in Large Granular Lymphocytic (LGL) Leukemia|
- Complete, Partial, and Overall Response Rates of Treatment With MTX, and Also With CY for Patients Failing to Respond to MTX [ Time Frame: Assessed during the first 4 months, then at least every three months for two years. Then every six months until five years after study entry, and every 12 months thereafter until full study stop date. ] [ Designated as safety issue: No ]We will report the overall response rate below. Complete remission requires that all of the following be present for at least four weeks: The patient must have a normal CBC including neutrophil count > 1500/mm3, lymphocyte count< 4000/mm3, hemoglobin > 11 g/dl, and platelet count > 100,000/mm3. In addition, the patient must have a normal LGL count. A complete response will be attained if CD8+ cells were less than 760/mm³. A partial response will be defined as achievement of any one of the following in the absence of CR. The response must last for at least four weeks:In patients being treated for severe neutropenia (less than 500 neutrophils/mm3) an improvement to over 500 neutrophils/mm3 will be considered a partial response, as long as that improvement represents at least a 50% impr
- Clinical Response [ Time Frame: Assessed during the first 4 months of treatment and followed until reaching full study stop date ] [ Designated as safety issue: No ]
|Study Start Date:||July 1999|
|Study Completion Date:||March 2012|
|Primary Completion Date:||December 2010 (Final data collection date for primary outcome measure)|
Experimental: Methotrexate (Cy if no response to MTX)
MTX given orally at 10 mg/m2 in divided doses once weekly. Prednisone was given orally at 1 mg/kg per day for 30 days and then tapered off in the subsequent 24 days. Patients not responding to MTX after 4 months received Cy orally at 100 mg daily in step two with the same prednisone schedule.
Patients not responding to MTX after 4 months received Cy orally at 100 mg daily in step two with the same prednisone schedule. In patients showing a partial response, but not a CR, the maximum period of therapy was 1 year.Drug: Methotrexate
Initial treatment consisted of MTX given orally at 10 mg/m2 in divided doses once weekly.Drug: Prednisone
Prednisone was given orally at 1 mg/kg per day for 30 days and then tapered off in the subsequent 24 days.
LGL leukemia is characterized by clonal expansion of cytotoxic T cells. Prominent clinical features include neutropenia, anemia, and rheumatoid arthritis. The terminal effector memory phenotype (CD3+/CD8+/CD57+/CD45RA+/CD62L-) of leukemic LGL suggest a pivotal chronic antigen driven immune response. LGL survival is then promoted by PDGF and IL-15, resulting in global dysregulation of apoptosis and resistance to normal pathways of activation-induced death. These pathogenic features explain why treatment of LGL leukemia is based on immunosuppression therapy. However, no standard therapy has been established due to the absence of large prospective trials.
Oral low dose MTX has been shown to be efficacious in the treatment of neutropenia. However, response to MTX is slow, requiring several months for the neutrophil count to increase above 500/mm3. Also, complete clinical remission may not be achieved until after one year of MTX therapy. Oral Cy has been the primary drug used for the treatment of severe transfusion-dependent anemia. Beneficial clinical effects are seen despite this treatment having no apparent effect on the abnormal LGL clone. Normal hematocrits are maintained after cessation of Cy and these results contrast the effects seen with MTX, in which clinical remissions are often associated with the disappearance of the clone.
This phase II trial undertaken by the Eastern Cooperative Group (ECOG) was initiated to investigate the mechanism of treatment response in patients with LGL leukemia, who need treatment for anemia or neutropenia.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00003910
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|Study Chair:||Thomas P. Loughran, MD||Milton S. Hershey Medical Center|