A Phase II Study of Initial Treatment With Methotrexate in Large Granular Lymphocytic (LGL) Leukemia
Cyclophosphamide
+ Methotrexate
+ Prednisone
Chronic Disease+15
+ Hematologic Diseases
+ Hemic and Lymphatic Diseases
Treatment Study
Summary
Study start date: September 15, 1999
Actual date on which the first participant was enrolled.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.
Protocol
This section provides details of the study plan, including how the study is designed and what the study is measuring.59 patients to be enrolled
Total number of participants that the clinical trial aims to recruit.Treatment Study
Eligibility
Researchers look for people who fit a certain description, called eligibility criteria: person's general health condition or prior treatments.Any sex
Biological sex of participants that are eligible to enroll.Over 18 Years
Range of ages for which participants are eligible to join.Healthy volunteers not allowed
If individuals who are healthy and do not have the condition being studied can participate.Conditions
Pathology
Criteria
Inclusion: Phenotypic studies from peripheral blood showing CD3+, CD57+ cells greater than 400/mm3 or CD8+ cells greater than 650/mm3 within eight weeks prior to registration Evidence for clonal T-cell receptor gene rearrangement within one year prior to registration At least one of the following: Severe neutropenia less than 500/mm3, neutropenia associated with recurrent infections, symptomatic anemia, or transfusion-dependent anemia Bilirubin ≤ 2.0 mg/dl, SGOT(AST) ≤ 1.5 times normal, and Creatinine ≤ 2.0 mg/dl within 4 weeks prior to registration ECOG performance status of 0-2 At least 18 years of age Written informed consent Exclusion: Prior therapy with oral MTX or oral Cy Previous or concurrent malignancies except inactive non-melanoma skin cancer, in situ carcinoma of the cervix, or other cancer if the patient has been disease free for over 5 years Pregnant or breast-feeding for female patients Serious medical illness, other than that treated by the study, which would limit survival to less than 2 years, or psychiatric condition which would prevent informed consent Note: to be eligible for step 2 of this study, patients were required to have no response after at least 4 months of methotrexate treatment.
Study Plan
Find out more about all the medication administered in this study, their detailed description and what they involve.One single intervention group is designated in this study
This study does not include a placebo group
Treatment Groups
Group I
ExperimentalStudy Objectives
Primary Objectives
Secondary Objectives
Study Centers
These are the hospitals, clinics, or research facilities where the trial is being conducted. You can find the location closest to you and its status.This study has 68 locations
Boulder Community Hospital
Boulder, United StatesPenrose Cancer Center at Penrose Hospital
Colorado Springs, United StatesSt. Anthony Central Hospital
Denver, United States