PHASE IA/B TRIAL OF ANTICD3 AND INTERLEUKIN 2

ANTICD3 和白细胞介素 2 的 IA/B 期试验

• 批准号: 2464566
• 负责人: B L GAUSE
• 金额: --
• 依托单位: DIVISION OF CLINICAL SCIENCES - NCI
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/2464566
• 关键词: CD3 molecule; antitumor antibody; clinical research; clinical trial phase I; human subject; human therapy evaluation; interleukin 2; leukocyte activation /transformation; lymphokine activated killer cell; melanoma; neoplasm /cancer immunotherapy; renal cell carcinoma

Initial clinical trials with LAK cells and IL-2 are associated with partial or complete responses in approximately 20% of patients with renal cell carcinoma and melanoma. However, the comparison of the antitumor activity of IL-2 alone versus IL-2 in combination with LAK cells showed at best only a small clinical benefit from the LAK cells. A recently completed phase I trial at the Frederick CRB using IL-2 and in vitro anti-CD3 activated T cells revealed an unexpectedly low response rate. One limitation of this trial is the fact that only cells that are circulated in the peripheral blood can be activated. Preclinical studies suggest that in a tumor in which CD8+ cells are the mode of rejection, the timing of anti-CD3 and IL-2 injection are of major importance. Based on these considerations, we propose to administer immunologically active doses of anti-CD3 in vivo to cancer pts. simultaneously with bolus and continuous infusion IL-2. The objectives of this study are: to determine whether anti-CD3 can be safely administered in combination with IL-2; to determine the toxicity of this regimen, to measure selective immunomodulatory effect; to observe any antitumor responses, and determine whether expansion of activated T lymphocytes can be achieved in vivo by this method. Pts. will receive anti-CD3 (400, 800, 1200, & 800 mu/m2), continuous infusion IL-2 (IV- IL2 0.75 mu/m2), and bolus IL-2 (1.5 mu/m2). Cohort 4 will receive cytoxan. 12 pts. have been entered on this study to date. There have been 2 PR's. Pts. have sustained significant toxicity including hypotension, chills, fever, and metabolic acidosis. The hypotension has been more pronounced than with similar doses of IL-2 alone. These have been manageable. We plan to accrue a total of 24 pts.

LAK 细胞和 IL-2 的初步临床试验与 大约 20% 的肾病患者部分或完全缓解 细胞癌和黑色素瘤。 但抗肿瘤作用比较 单独的 IL-2 活性与 IL-2 与 LAK 细胞组合的活性相比，显示 最好只能从 LAK 细胞中获得很小的临床益处。 最近一个 在 Frederick CRB 完成了使用 IL-2 和体外的 I 期试验 抗 CD3 激活的 T 细胞显示出出乎意料的低反应率。 该试验的一个局限性是，只有细胞 可以激活末梢血液循环。 临床前研究 表明在以 CD8+ 细胞为排斥模式的肿瘤中， 抗 CD3 和 IL-2 注射的时机非常重要。 基于 考虑到这些因素，我们建议给予免疫活性药物 癌症患者体内抗 CD3 剂量。同时与推注和 持续输注IL-2。 本研究的目的是：确定 抗CD3是否可以安全地与IL-2联合给药；到 确定该方案的毒性，以测量选择性 免疫调节作用；观察任何抗肿瘤反应，并确定 活化T淋巴细胞的扩增是否可以通过以下方式在体内实现 这个方法。 分。将接受抗 CD3（400、800、1200 和 800 mu/m2）， 连续输注IL-2（IV-IL2 0.75 mu/m2）和推注IL-2（1.5 mu/m2）。 第 4 组将接受环磷酰胺。 12分已经进入这项研究 日期。 已有 2 个 PR。 分。具有持续显着的毒性 包括低血压、寒战、发烧和代谢性酸中毒。 这 低血压比相似剂量的 IL-2 更明显 独自的。 这些都是可以管理的。 我们计划总共获得 24 分。