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

这是一项单一机构前瞻性随机研究，研究对象为131人 碘-抗-B1 RIT与未标记抗-B1单抗联合治疗 化疗耐药的低度B细胞淋巴瘤患者。这个 本研究的目标是评估递增的临床活动 放射性标记小鼠抗CD20单抗的毒性研究 ~(131)I标记抗-B1与未标记抗-B1在患者中的比较 复发的低级别非霍奇金淋巴瘤(NHL) 随机试验。这项研究正在对患有以下疾病的患者进行 化疗难治(耐阿霉素或抗烷化剂) 完成治疗后一年内进展的低级别NHL 最后的化疗方案。先用131I-抗-B1治疗的患者 立即输注未标记的抗-B1，之后立即注射 用5mCI~(131)I示踪的抗铋静脉滴注。 示踪剂剂量超标对全身的辐射剂量 大约一周是从放射性清除计算出来的 数据。根据这些针对每个人的计算 病人，给予131I-抗铋的RIT剂量，以便全身 辐射剂量为75cGy.在未标记的抗体臂中， 患者将接受等量的未标记B1。部分 患者可以单向交叉到抗B1RIT臂 随着疾病的进展，使用未标记的抗-B1治疗。 用放射性标记的抗-B1重新治疗也将允许 两种标记物对同一患者治疗反应的比较 和未标记的抗-B1。双方的反应将在六点后进行评估 12周后，每12周间隔一次，最多两周后 最后一位病人入院后的几年。交叉可能需要 在最后一名患者登记后最多21个月。 到目前为止，结果相当令人鼓舞。在六名患者中 在初步剂量学研究中接受治疗(所有患者均接受131次剂量 I-抗-B1估计对全身产生75cGy射线)和4 接受上述随机研究的患者。一种回应 目前利率为100%。在前6名患者中，有4个CRS(3 正在进行，FFP=24周以上，1个FFP=24周)，2个PR使用FFP 12周和12周以上。在随机研究中观察到了两个PR (在未标记的臂中FFP=12wk，在131I-抗B1臂中FFP=6+wk) 在2名获得足够长时间随访的患者中， 回应。这些疗法耐受性很好，而且唯一的 正如预期的那样，显著的毒性是可逆的肌肉抑制。 这项研究将继续进行，直到28名患者得到治疗(14名患者在 研究的每一臂)。

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.