The dosing regimen and maximally tolerated dose of Bexxar were established in a phase I/II single-center study conducted at the University of Michigan (Kaminski et al, 2000). The RIT-II-001 trial included 47 patients and was designed to validate the dosing methodology developed at Michigan (Vose et al, 2000). The RIT-II-002 trial randomized 78 patients to receive either the tositumomab and I 131-tositumomab regimen or the unlabeled tositumomab to determine the value added of the radionuclide component (Davis et al, 2001). Patients treated on the radiolabeled antibody arm showed a higher overall response rate (OR = 55% vs. 19%) and complete response rate (CR = 33% vs. 8%). The RIT-II-004 study enrolled 60 patients with chemotherapy-refractory disease (no response or response lasting less than 6 months to the last chemotherapy received) to assess the efficacy of the Bexxar therapeutic regimen in this patient population (Kaminski et al, 2001). The number of patients who achieved longer duration of response to Bexxar was about 5 times higher than the number of patients who had a longer duration to chemotherapy (p <0.001). In addition, patients treated with Bexxar achieved a higher overall response (OR) rate (47% vs. 12%) and complete response (CR) rate (20% vs. 2%) than patients treated with chemotherapy. In summary, all 4 initial studies, including the Phase I/II trial, showed high response rates and duration of responses in patients with relapsed or refractory low grade or follicular lymphoma, including transformed follicular lymphoma previously-treated with chemotherapy. Most remarkably, patients who achieved complete responses experienced often particularly long duration of responses lasting for years. In recognition of remarkable activity, the FDA approved an expanded indication for the Bexxar Therapeutic Regimen on January 3, 2005.