ANTI-B1 (MURINE) IN CHEMOTHERAPY-REFRACTORY LOW GRADE NONHODGKIN'S LYMPHOMA

这是一项多中心、前瞻性、随机研究，比较了131例化疗难治性低度B细胞淋巴瘤患者接受碘-抗B1 RIT和未标记抗B1单克隆抗体治疗的情况。本研究的目的是在一项对照和随机试验中评估放射性标记鼠单克隆抗CD 20抗体（抗B1）与未标记抗B1相比对复发性低度非霍奇金淋巴瘤（NHL）住院患者的增量临床活性和毒性。本研究在完成最后一次化疗方案后一年内进展的化疗难治性（阿霉素耐药或烷化剂耐药）低度NHL患者中进行。接受131 I-抗B1治疗的患者首先接受未标记抗B1输注，随后立即输注已用4 mCi 131 I进行痕量标记的抗B1。根据放射性清除数据计算约一周内由示踪剂剂量递送至全身的辐射剂量。根据这些针对每个患者的计算，给予131 I-抗B1的RIT剂量，从而输送75 cGy的全身辐射剂量。在未标记抗体组中，患者将接受等量的未标记B1。对于疾病进展后接受未标记抗B1治疗的患者，可以部分单向交叉至抗B1 RIT组。放射性标记抗B1治疗还将允许比较同一患者接受标记和未标记抗B1治疗的反应。将在6周后、12周后和此后每隔12周评估一次两组的缓解，直至最后一例患者入组后2年。交叉可以在最后一例患者入组后21个月内进行。迄今为止，结果相当令人鼓舞。在初步剂量测定研究中接受治疗的6名患者中（所有患者均接受了131 I-抗B1剂量，估计全身剂量为75 cGy）。有效率为100%，4例CR和2例PR。在随机化研究中，入组了20例患者。当对9/97例治疗后> 6周且可评价应答的15例患者进行中期分析时，与单独抗B1抗体相比，131 I-抗B1抗体有更大疗效的趋势，应答率为75%对43%，CR率为25%对14%。此外，接受131 I-抗B1治疗的患者的缓解持续时间通常更长。此后未进行中期分析。治疗耐受性良好，唯一显著的毒性是可逆的骨髓抑制，如预期。本研究将持续至26例患者接受治疗（研究每组13例），如方案所述。

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.