Trial Information

Phase III Trial of CHOP Versus CHOP and Chimeric Anti-CD20 Monoclonal Antibody (IDEC-C2B8) in Older Patients With Diffuse Mixed, Diffuse Large Cell and Immunoblastic Large Cell Histology Non-Hodgkin's Lymphoma

OBJECTIVES: I. Compare the efficacy of CHOP (cyclophosphamide, doxorubicin, vincristine, and
prednisone) with or without rituximab in older patients with diffuse mixed, diffuse large,
or immunoblastic large cell non-Hodgkin's lymphoma of B-cell lineage with respect to the
response rate, time to treatment failure, toxicity, and survival. II. Compare the efficacy
of maintenance therapy consisting of rituximab vs observation alone after initial therapy
with respect to the time to treatment failure, duration of response, toxicity, and survival
of this patient population. III. Determine if maintenance therapy with rituximab results in
the conversion of any partial response to complete response.

OUTLINE: This is a randomized study. For the first randomization, patients are stratified
according to the number of risk factors (0-1 vs 2-4). For the second randomization, in
addition to the number of risk factors, patients are stratified according to objective
response to initial induction therapy (partial response vs complete response) and induction
therapy (CHOP vs CHOP and rituximab). Patients are randomized to one of two treatment arms.
Arm I: Patients receive CHOP chemotherapy comprising cyclophosphamide IV, doxorubicin IV,
and vincristine IV on day 1 and oral prednisone on days 1-5. Treatment repeats every 21 days
in the absence of unacceptable toxicity. Arm II: Patients receive treatment as in arm I.
Patients also receive rituximab IV on days -7,-3, 41, and 83. Patients who achieve complete
response (CR) after 4 courses of CHOP and remain in CR after 6 courses of CHOP are further
randomized to one of two arms. Arm I (Maintenance therapy): Patients receive rituximab IV
weekly for 4 weeks. Courses repeat every 6 months for 2 years in the absence of unacceptable
toxicity. Arm II: Patients are observed. Patients who achieve partial response (PR) after 6
courses OR PR after 4 courses and then CR after 6 courses receive 2 additional courses of
CHOP therapy. Patients are then also randomized to receive either maintenance therapy or
observation as above. Patients with stable disease or disease progression are removed from
the study. Patients are followed every 3 months for 2 years, every 6 months for 3 years, and
then annually thereafter.

PROJECTED ACCRUAL: Approximately 630 patients will be accrued for this study within 4 years.