Clinical trial NCT00003910
Conditions: Leukemia
Keywords: stage I chronic lymphocytic leukemia stage II chronic lymphocytic leukemia stage III chronic lymphocytic leukemia stage IV chronic lymphocytic leukemia T-cell large granular lymphocyte leukemia LGL clone
Sponsor: Eastern Cooperative Oncology Group
Start date: 1999-09-15; Completion date: 2012-03-01
Enrollment: 59 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
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.

Detailed description:
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.

Arms: arm 1: 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.
Interventions: intervention 1: Cyclophosphamide intervention 2: Methotrexate intervention 3: Prednisone
Intervention descriptions: intervention 1: 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. intervention 2: Initial treatment consisted of MTX given orally at 10 mg/m2 in divided doses once weekly. intervention 3: Prednisone was given orally at 1 mg/kg per day for 30 days and then tapered off in the subsequent 24 days.

Protocol documents: