Trial Information

Iodine-131-Labeled Monoclonal Anti-B1 Antibody (I-131 Tositumomab) in Combination With Cyclophosphamide, Doxorubicin, Vincristine, Prednisone and Rituximab Therapy for Patients ≥ Age 60 With Advanced Stage Diffuse Large B-Cell NHL: A Phase II Study

OBJECTIVES:

- Determine the 2-year progression-free survival of older patients with previously
untreated bulky stage II or stage III or IV diffuse large B-cell non-Hodgkin's lymphoma
treated with iodine I 131 tositumomab in combination with rituximab, cyclophosphamide,
doxorubicin, vincristine, and prednisone.

- Determine the response rate (partial response, complete unconfirmed response, and
complete response) in patients treated with this regimen.

- Determine the 2-year progression-free survival and response rate (partial response,
complete unconfirmed response, and complete response) in BCL-2 positive patients
treated with this regimen.

OUTLINE: This is a multicenter study.

- Rituximab and chemotherapy: Patients receive R-CHOP comprising rituximab IV over 6
hours; cyclophosphamide IV over 15-45 minutes; doxorubicin IV over 5-20 minutes; and
vincristine IV over 5-15 minutes on day 1 and oral prednisone on days 1-5. Treatment
repeats every 21 days for up to 6 courses in the absence of disease progression or
unacceptable toxicity. Patients then undergo a restaging evaluation. Patients without
progressive disease receive CHOP chemotherapy comprising cyclophosphamide, doxorubicin,
vincristine, and prednisone as outlined above. Treatment with CHOP chemotherapy repeats
every 21 days for 2 courses.

- Radiolabeled monoclonal antibody therapy: Approximately 4-8 weeks after completion of
chemotherapy, patients receive tositumomab IV over 1 hour followed by a dosimetric dose
of iodine I 131 tositumomab IV over 20 minutes. Patients then undergo gamma scans over
a 1-week period in order to determine the correct treatment dose of iodine I 131
tositumomab. No more than 2 weeks after administration of the dosimetric dose, patients
receive tositumomab IV over 1 hour followed by a treatment dose of iodine I 131
tositumomab IV over 20 minutes.

After completion of study treatment, patients are followed periodically for up to 5 years.

PROJECTED ACCRUAL: A total of 80 patients will be accrued for this study within 15 months.