TREATMENT OF B-CELL LYMPHOMAS WITH ANTI-B4-BLOCKED RICIN IMMUNOCONJUGATE

本研究是一项针对低级别淋巴瘤患者的II期治疗 或慢性淋巴细胞白血病，包括治疗和未治疗的 患者 该免疫毒素是抗B4阻断的蓖麻毒素，并且包括抗B4阻断的蓖麻毒素。 识别CD 19的单克隆抗体（其是 存在于大多数B细胞恶性肿瘤）和阻断蓖麻毒素（其中B- 毒素链已被阻断）。 免疫毒素在24小时内注射 连续输注7天。治疗重复 每14天。 临床应答是终点。 迄今为止， 淋巴瘤患者已进入本研究。 所述第一患者 接受抗B4阻断蓖麻毒素50 mcg/kg/天，但停止输注 由于不可接受的毒性而过早（第5天）。 患者于 研究第7天，可能由于毛细血管 渗漏综合征 随后，将免疫毒素的剂量降低至 30 mcg/kg/天，并根据瘦体重而非实际体重进行调整 重量. 另有5名患者接受了该较低剂量的治疗 只有中等毒性。 在接受治疗的6名患者中， 一个病情稳定，一个病情进展。三名患者 病情稳定，未接受进一步治疗。两 患者死于进行性淋巴瘤。

This study is a Phase II treatment for patients with low grade lymphomas or chronic lymphocytic leukemia and includes both treated and untreated patients. The immunotoxin is anti-B4-blocked ricin, and includes a conjugate between a monoclonal antibody that recognizes CD19 (which is present on most B-cell malignancies) and blocked ricin (in which the B- chain of the toxin has been blocked). The immunotoxin is given by 24-hour continuous infusion for seven consecutive days. Treatment is repeated every 14 days. Clinical response is the endpoint. To date, six low grade lymphoma patients have been entered onto this study. The first patient received anti-B4-blocked ricin 50 mcg/kg/day, but the infusion was stopped prematurely (on day 5) due to unacceptable toxicity. The patient died on day seven of the study with refractory hypotension likely due to capillary leak syndrome. Subsequently, the dose of the immunotoxin was decreased to 30 mcg/kg/day and adjusted per lean body weight rather than actual body weight. An additional 5 patients have been treated at this lower dose level with only moderate toxicity. Among the six patients treated, five had stable disease and one had progressive disease. Three patients continue to have stable disease and have received no further therapy. Two patients have died with progressive lymphoma.