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

这是一项单机构前瞻性随机研究， 碘-抗B1 RIT和未标记抗B1单克隆抗体治疗 化疗难治性低度恶性B细胞淋巴瘤患者。 的 本研究的目的是评估增量临床活动 放射性标记鼠抗CD 20单克隆抗体的毒性 （抗B1）与131碘相比，患者中未标记的抗B1 在对照组中， 随机试验 本研究在以下患者中进行： 化疗难治性（多柔比星耐药或烷化剂耐药） 低级别NHL谁已经完成后一年内进展， 末次化疗方案。 首先接受131 I-抗B1治疗的患者 接受未标记抗B1输注，然后立即 输注抗Bi，其已被5 mCi的131 I标记。 由示踪剂剂量传递到全身的辐射剂量超过 根据放射性清除率计算约1周 数据 根据这些针对每个人的计算 患者，给予131 I-抗Bi的RIT剂量，使得全身 输送75 cGy的辐射剂量。 在未标记的抗体臂中， 患者将接受等量的未标记的 B1. 部分 患者可能单向交叉至抗B1 RIT组 在疾病进展后接受未标记抗B1治疗。 放射性标记抗B1再治疗还将允许 比较用两种标记药物治疗的同一患者的反应 和未标记的抗B1抗体两组的反应将在6小时后进行评估。 12周后和12周后间隔， 最后一名患者入组后数年。 交叉可以采取 最后一名患者入组后21个月内。 迄今为止，结果相当令人鼓舞。 在6名患者中 在初步剂量测定研究中接受治疗（所有患者均接受131 I-抗-B1估计向全身递送75 cGy）和4 在上述随机化研究中接受治疗的患者。 一个响应 目前的比例是100%。 在前6例患者中，有4例CR（3 持续FFP = 24+周，1例FFP=24周）和2例FFP PR 12 x和12+周。 在随机化研究中观察到2例PR (FFP未标记组=12周，131 I-抗B1组FFP=6+周） 2例患者随访时间足够长， 反应 这些治疗的耐受性很好， 如预期的，显著的毒性是可逆的骨髓抑制。 这项研究将继续进行，直到28名患者接受治疗（14名患者接受治疗）。 每个研究组）。

This is a single institution prospectively randomized study between 131 Iodine-Anti-B1 RIT and unlabeled Anti-B1 monoclonal antibody therapy for patients with chemotherpy-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 in patients with relapsed low-grade non-Hodgkin's lymphome (NHL) in a controlled and randomized trial. This study is being conducted in patients with chemotherapy-refractory (doxorubicin-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 receive an infusion of unlabeled Anti-B1 immediately followed by an infusion of Anti-Bi which has been trace labeled with 5 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-Bi is given so that a whole body radiation dose of 75 cGy is delivered. In the unlabled antibody arm, patients will receive 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 retreatment 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 therafter up to two years following enrollment of the last patient. Crossover can take place up to 21 months following the enrollement 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) and four patients treated on the randomized study described above. One response rate is currently 100%. In the first 6 patients there are four CRs (3 ongoing with FFP = 24+ wks and one with FFP=24 wk) and 2 PRs with FFP 12x and 12+ weeks. Two PRs have been observed in the randomized study (FFP=12 wk in the unlabeled arm and FFP=6+wk in the 131 I-Anti-B1 arm) in 2 patients with follow-up of long enough duration to more the response. The treatments have been very well tolerated and the only significant toxicity has been reversible mylosuppression as expected. This study will be continued until 28 patients have been treated (14 in each arm of the study) as described in the protocol.