Randomized Phase III Study in Low Grade Lymphoma Comparing Maintenance Anti-CD20 Antibody Versus Observation Following Induction Therapy
I. To compare the response rate, time to progression, time to treatment failure, and
survival for patients with low grade lymphoma treated with the cyclophosphamide -
fludarabine regimen with a control arm consisting of standard treatment with CVP.
II. To determine the effect of maintenance with anti-CD20 (IDEC C2B8) on time to
progression, time to treatment failure, and survival and its effects on lymphocyte number,
subsets, and quantitative immunoglobulin levels over time.
OUTLINE: This a two step, stratified, randomized study. Patients are stratified for arms I
and II (step 1) by age (under 60 vs 60 and over), tumor burden (high vs low), histology
(follicular vs other), and B symptoms (present vs absent). After arms I and II have been
completed, patients are stratified in arms III and IV (step 2) by extent of residual disease
(minimal vs gross), histology (follicular vs other), and initial tumor burden.
ARM I (CLOSED AS OF 9/2000): Patients receive cyclophosphamide IV over 30-45 minutes on day
1 and fludarabine IV over 10-20 minutes on days 1-5. Treatment repeats every 28 days in the
absence of disease progression for a minimum of 4 courses and a maximum of 6 courses.
ARM II: Patients receive cyclophosphamide IV over 30-45 minutes and vincristine IV on day 1,
and oral prednisone on days 1-5. Treatment repeats every 21 days in the absence of disease
progression for a minimum of 6 courses and a maximum of 8 courses.
After completion of therapy on arm I or II, patients are randomized into step 2 of this
study comprising arms III and IV.
ARM III: Patients receive maintenance therapy with rituximab (IDEC-C2B8 monoclonal antibody)
IV weekly for 4 weeks. Courses repeat every 6 months for 2 years. Maintenance therapy begins
4 weeks after the last chemotherapy.
ARM IV: Patients undergo no maintenance therapy and are observed.
Patients are followed every 3 months for 2 years, every 6 months for the next 3 years, and
then annually thereafter.
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Time to treatment failure
This comparison will be made using a one-sided logrank test with a 5% type I error rate.
From maintenance randomization to the earlier of progression or death, assessed up to 5 years
Eastern Cooperative Oncology Group
United States: Food and Drug Administration
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