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，131碘抗b1 RIT和未标记抗b1单克隆抗体治疗化疗难治性低级别b细胞淋巴瘤患者。本研究的目的是在一项对照和随机试验中评估131碘放射标记小鼠单克隆抗cd20抗体（抗b1）与未标记抗b1复发低级别非霍奇金淋巴瘤（NHL）住院患者的临床活性和毒性。这项研究是在化疗难治性（阿霉素耐药或烷基化剂耐药）低级别NHL患者中进行的，这些患者在完成最后一次化疗方案后一年内进展。接受131 i-抗- b1治疗的患者首先接受未标记的抗- b1输注，随后立即输注被标记为131 i的4mci的抗- b1。示踪剂在大约一周内对全身的辐射剂量是根据放射性清除数据计算的。根据每个患者的具体计算，给予131 I-Anti-B1的RIT剂量，从而提供75 cGy的全身辐射剂量。在未标记抗体组，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，部分单向交叉到抗- b1 RIT组将是可能的。使用放射性标记的抗- b1治疗还可以比较使用标记和未标记的抗- b1治疗的同一患者的反应。两组患者的反应将在最后一名患者入组后的6周后、12周后和12周后进行评估。交叉治疗可在最后一名患者入组后最多21个月内进行。迄今为止，结果相当令人鼓舞。在初步剂量学研究中接受治疗的6名患者中（所有患者均接受131 I-Anti-B1剂量，估计向全身输送75 cGy）。4个cr和2个pr的应答率为100%。在这项随机研究中，20名患者入组。1997年9月进行的中期分析显示，15名患者在治疗后6周内可评估反应，与单独使用抗b1抗体相比，131 I-Anti-B1有更大的疗效趋势，反应率为75%对43%，CR率为25%对14%。此外，接受131 I-Anti-B1治疗的患者的反应持续时间通常更长。此后再无中期分析。治疗的耐受性很好，唯一显著的毒性如预期的那样是可逆的骨髓抑制。这项研究将继续进行，直到26名患者接受治疗（研究每组13名）。

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.