This is a multicenter prospectively randomized study between 131 Iodine-Anti-B1 RIT and unlabeled Anti-B1 monoclonal antibody therapy for patients with chemotherapy-refractory low-grade B-cell lymphomas. The objectives of this study are to assess the incremental clinical activity and toxicity of radiolabeling murine monoclonal Anti-CD20 antibody (Anti-B1) with 131 Iodine as compared to unlabeled Anti-B1 inpatients with relapsed low-grade non-Hodgkin's lymphoma (NHL) in a controlled and randomized trial. This study is being conducted in patients with chemotherapy-refractory (doxiorubicin-resistant or alkylator-resistant) low-grade NHL who have progressed within one year after completing the last chemotherapy regimen. Patients treated with 131 I-Anti-B1 first received an infusion of unlabeled Anti-B1 immediately followed by an infusion of Anti-B1 which has been trace labeled with 4 mCi of 131I. The radiation dose to the whole body delivered by the tracer dose over approximately one week is calculated from the radioactivity clearance data. Based upon these calculations specific for each individual patient, a RIT dose of 131 I-Anti-B1 is given so that a whole body radiation dose of 75 cGy is delivered. In the unlabeled antibody arm, patients will received an equivalent amount of unlabeled B1. Partial one-way crossover to the Anti-B1 RIT arm will be possible for patients treated with unlabeled Anti-B1 following progression of the disease. This treatment with radiolabeled Anti-B1 will also allow for comparison of responses in the same patient treated with both labeled and unlabeled Anti-B1. Response in both arms will be assessed after six weeks, after 12 weeks and in 12 weekly intervals thereafter up to two years following enrollment of the last patient. Crossover can take place up to 21 months following the enrollment of the last patient. To date, the results have been quite encouraging. In six patients treated on the preliminary dosimetry study (all received a dose of 131 I-Anti-B1 estimated to deliver 75 cGy to the whole body). The response rate is 100% with four CRs and 2 PRs. In the randomized study, 20 patients have been enrolled. When an interim analysis was performed 9/97, of fifteen patients > 6 weeks out from treatment and evaluable for response, there is a trend towards greater efficacy with 131 I-Anti-B1 as compared to Anti-B1 antibody alone with response of 75% vs. 43% and CR rates of 25% vs. 14%. In addition, the duration of response is generally higher in patients treated with 131 I-Anti-B1. There has been no interim analysis since. The treatments have been very well tolerated and the only significant toxicity has been reversible mylosuppression as expected. This study will be continued until 26 patients have been treated (13 in each arm of the study) as described in the protocol.
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