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

这是一项在131I-抗-B1RIT和未标记抗-B1单抗治疗化疗难治的低度B细胞淋巴瘤患者之间进行的多中心前瞻性随机研究。本研究的目的是在一项对照和随机试验中，以未标记的低度非霍奇金淋巴瘤(NHL)住院患者为对照，评价131I放射性标记鼠源性抗CD20单抗(抗-B1)的临床活性和毒性。这项研究是在化疗耐药(阿霉素耐药或烷化剂耐药)低级别非霍奇金淋巴瘤患者中进行的，他们在完成最后一次化疗方案后一年内进展。接受131I-抗-B1治疗的患者首先立即输注未标记的抗-B1，然后输注已标记有4mCI的131I的抗-B1。根据放射性清除数据计算示踪剂剂量在大约一周内对全身的辐射剂量。根据这些针对每个患者的具体计算，给出了131I-抗-B1的RIT剂量，以便提供75cGy的全身辐射剂量。在未标记抗体臂中，患者将接受等量的未标记B1。随着疾病的进展，部分单向交叉到抗B1 RIT臂的患者将有可能接受未标记的抗B1治疗。这种放射性标记的抗-B1治疗也将允许比较标记和未标记抗-B1治疗同一患者的反应。在最后一名患者入选后的两年内，将在6周后、12周后和此后每12周一次的间隔时间内评估双方的反应。在最后一名患者登记后21个月内可以进行交叉试验。到目前为止，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(所有患者都接受了131I-抗-B1剂量，估计可向全身提供75cGy射线)。4个CR和2个PR的有效率为100%。在这项随机研究中，有20名患者入选。当进行9/97的中期分析时，15名患者在接受治疗6周后可评估疗效，与单独使用抗B1抗体相比，131I-抗-B1有更好的疗效，有效率分别为75%和43%，CR率分别为25%和14%。此外，接受131I-抗-B1治疗的患者的反应持续时间一般更长。自那以后，没有进行过中期分析。这些治疗耐受性很好，唯一显著的毒性是如预期的可逆性肌球抑制。这项研究将继续进行，直到26名患者得到治疗(研究的每一组13人)，如方案中所述。

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.