Methotrexate With or Without Cyclophosphamide in Treating Patients With Lymphocytic Leukemia

Phase 2TerminatedNCT00003910

Eastern Cooperative Oncology Group59 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Leukemia

Interventions

CyclophosphamideDRUG

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.

MethotrexateDRUG

Initial treatment consisted of MTX given orally at 10 mg/m2 in divided doses once weekly.

PrednisoneDRUG

Prednisone was given orally at 1 mg/kg per day for 30 days and then tapered off in the subsequent 24 days.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Locations (68)

Outcomes

Primary Outcomes

Proportion of Patients With Complete or Partial Response to Treatment With MTX

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% improvement.

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.

Secondary Outcomes

Proportion of Patients With Complete or Partial Response to Treatment of CY Among Patients Failing to Respond to MTX

Time frame: Assessed during the first 4 months of treatment and followed until reaching full study stop date

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

Aurora Presbyterian Hospital

Aurora, Colorado, United States

Boulder Community Hospital

Boulder, Colorado, United States

Penrose Cancer Center at Penrose Hospital

Colorado Springs, Colorado, United States

St. Anthony Central Hospital