Advanced-Stage Follicular Non-Hodgkin Lymphoma

 SWOG 0801 – A Phase II Study of Iodine-131-Labeled Tositumomab in Combination With Cyclophosphamide, Doxorubicin, Vincristine, Prednisone, and Rituximab (RCHOP) Therapy for Patients With Advanced-Stage Follicular Non-Hodgkin Lymphoma

 Southwest Oncology Group (SWOG) with NCI collaboration

 NCT00770224

 125 SWOG-affiliated centers throughout the United States

 80 patients

 A Phase II study design in which patients with bulky-stage II or advanced-stage (III/IV) follicular lymphoma (low grade and grade III) in need of treatment will receive RCHOP induction, consolidation with I-131 tositumomab (radiolabeled anti-CD20), and maintenance therapy with rituximab.

 Follicular lymphoma (FL) is the most common indolent B-cell lymphoproliferative disorder diagnosed in the United States. Generally, the initial response to treatment of FL is excellent, but relapses are considered inevitable, and progressive shortening of response duration characterizes the course of subsequent treatments. The high degree of sensitivity of FL to a variety of chemotherapeutic agents suggests the possibility of cure, but that goal has proven to be frustratingly elusive. Until the addition of rituximab, most cooperative group studies, including those sponsored by SWOG, failed to show improvement in overall survival despite the use of a number of different therapeutic strategies. Rituximab, a mouse/human chimeric anti-CD20 humanized antibody, has remarkable efficacy in FL, and its use in combination with chemotherapy regimens has improved overall survival in both upfront and relapsed/refractory settings. Additionally, maintenance therapy with rituximab has been reported to prolong progression-free survival (PFS) in patients with FL when added to initial treatment regimens that included rituximab. Single-agent radioimmunotherapy is efficacious as treatment for FL as both initial and salvage therapy, and previous SWOG studies showed that CHOP + I-131 tositumomab is a feasible and effective treatment for FL. Additionally, that group showed that RCHOP followed by radioimmunotherapy could be given safely to patients with diffuse large B-cell lymphoma. Together, these observations suggested a logical next step in the pursuit of improved treatment of FL. In SWOG 0801, patients are treated with RCHOP for six cycles, consolidated with I-131 tositumomab, and then given maintenance therapy with rituximab every three months for four years. The primary endpoint of the study is determination of three-year PFS, with PFS of 79 percent or better being the predetermined benchmark that if reached would trigger further investigation. Secondary endpoints are response rate, five-year PFS, and overall survival.

 This regimen represents an aggressive initial treatment strategy for FL. If no clear benefit compared with historical data is observed, a phase III trial that uses radioimmunotherapy in combination with RCHOP and rituximab would be difficult to support. A positive outcome, however, would serve as the foundation for phase III studies, with the goal of answering a number of questions, including: What is the optimal chemotherapy regimen; what is the optimal dose and length of rituximab maintenance therapy; what is the impact on overall survival; what is the cost of the regimen; and what are the long-term consequences of treatment?