S0019 Combination Chemotherapy With or Without Rituximab in Treating Patients With Relapsed or Refractory Non-Hodgkin's Lymphoma

Overview

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Monoclonal antibodies such as rituximab can locate cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. It is not yet known whether combination chemotherapy is more effective with or without rituximab for non-Hodgkin's lymphoma. PURPOSE: Randomized phase III trial to compare the effectiveness of combination chemotherapy with or without rituximab in treating patients who have relapsed or refractory non-Hodgkin's lymphoma.

OBJECTIVES: I. Compare the progression-free and overall survival of patients with relapsed or refractory, CD20 expressing, aggressive, B-cell non-Hodgkin's lymphoma treated with ifosfamide, carboplatin, and etoposide with or without rituximab. II. Compare the unconfirmed response rate of patients treated with these regimens. III. Determine the toxicity of ifosfamide, carboplatin, and etoposide with rituximab in these patients. OUTLINE: This is a randomized study. Patients are stratified according to histology (large B-cell vs other) and risk group (low/low-intermediate vs high-intermediate/high). Patients are randomized to one of two treatment arms. Arm I: Patients receive etoposide IV over 1 hour on days 1-3, carboplatin IV over 1 hour on day 2, ifosfamide IV continuously for 24 hours on day 2, and filgrastim (G-CSF) subcutaneously (SC) on days 5-12. Treatment continues every 3 weeks for 3 courses in the absence of disease progression or unacceptable toxicity. Arm II: Patients receive rituximab IV on day 1, etoposide IV over 1 hour on days 2-4, carboplatin IV over 1 hour on day 3, ifosfamide IV continuously for 24 hours on day 3, and G-CSF SC on days 6-13. Patients also receive rituximab IV on day 8 of course 1. Treatment continues every 3 weeks for 3 courses in the absence of disease progression or unacceptable toxicity. Patients are followed every 3 months for 1 year, every 6 months for 2 years, and then annually for 5 years. PROJECTED ACCRUAL: A total of 376 patients (188 per arm) will be accrued for this study within 3 years.