MONOCLONAL ANTIBODY 81C6-131I METASTATIC TO LEPTOMENINGES

单克隆抗体 81C6-131I 转移至软脑膜

• 批准号: 6243988
• 负责人: MARK T BROWN
• 金额: $ 3.24万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1975
• 资助国家: 美国
• 起止时间: 1975-10-01 至 1998-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6243988
• 关键词: clinical research; human subject; human therapy evaluation; iodine; meningioma; monoclonal antibody; neoplasm /cancer immunotherapy; neoplasm /cancer radionuclide therapy

This protocol contains two components, each assigned a separate Duke IRB number. The first component utilizes 131I-labeled 81C6 monoclonal antibody in the treatment of patients with neoplastic meningitis or postoperative cystic brain tumor resection cavities communicating with CSF. The purpose of this study is to determine the efficacy of intrathecal 131I-labeled 81C6 monoclonal antibody in patients with neoplastic meningitis or postoperative cystic cystic brain tumor resection cavities communicating with CSF. The second component utilizes 131I-labeled 81C6 monoclonal antibody in the treatment of patients with malignant central nervous system tumors with surgically created cystic resection cavities (that do not communicate with CSF). The purpose of this study is to determine the efficacy of 131I-labeled 81C6 monoclonal antibody administered into surgically created cystic tumor resection cavities in patients with malignant central nervous system tumors. Both disease entities are devastating, incurable neurologic complications of cancer where present treatments are inadequate. The development of monoclonal antibodies has provided the potential for more specific therapy of tumors which are reactive with the monoclonal antibody or antibody fragment. Antibodies that are specific to the tumor cells and that do not react with normal brain or spinal cord can be conjugated with therapeutic radioisotopes, such as 131I. This conjugate can then be delivered intrathecally for leptomentingeal neoplasms or into a surgically-created resection cavity for brain tumors to deliver a therapeutic dose of radiation with relative specificity for the tumor cells. The Phase II study of 131I-labeled 81C6 monoclonal antibody for patients with neoplastic meningitis or postoperative cystic cavities communicating with CSF (CRU Protocol 753), builds on the successful completion of the Phase I study CRU Protocol 648 for patients with neoplasms metastatic to the leptomeninges. In the Phase II study, eligible patients are treated with monthly cycles of intrathecal 60 mCi 131I-labeled 81C6 monoclonal antibody (10 mg protein). Patients are evaluated for response each eight weeks. Response criteria are based on objective measures of CSF cytology and tumor size on MRI scanning. For patients with recurrent tumors, treatment continues until there has been a complete response for 12 cycles, stable disease for 12 cycles, progressive or recurrent disease as documented by MRI or physical exam, grade 4 nonhematologic toxicity or hematologic toxicity requiring reinfusion of the patient's previously stored peripheral stem cells. Patients with newly diagnosed tumors for which no effective conventional therapy exists, such as malignant glial tumors metastatic to the leptomeninges, are treated for 4 cycles and then referred to external beam radiotherapy unless progressive tumor is noted at an earlier time. The other criteria for treatment duration in newly diagnosed patients are the same as those for patients with recurrent tumors. For each of 5 histologic subgroups, a two-stage Phase II design which differentiates between a response rate of 10% and 30% will be used to evaluate the activity of intrathecal 131I-labeled 81C6.

该协议包含两个组件，每个组件分配一个单独的 Duke IRB 数字。第一个组件使用 131I 标记的 81C6 单克隆抗体 抗体用于治疗肿瘤性脑膜炎患者或 囊性脑肿瘤切除术后空腔与 脑脊液。 本研究的目的是确定功效 鞘内注射131I标记的81C6单克隆抗体 肿瘤性脑膜炎或术后囊性囊性脑肿瘤 切除腔与脑脊液相通。 第二个组成部分 利用 131I 标记的 81C6 单克隆抗体治疗 患有恶性中枢神经系统肿瘤并接受手术治疗的患者 创建囊性切除腔（不与脑脊液连通）。 本研究的目的是确定 131I 标记的功效 将 81C6 单克隆抗体注入手术产生的囊肿中 中枢性恶性肿瘤患者的肿瘤切除腔 神经系统肿瘤。 这两种疾病都是毁灭性的、无法治愈的 目前的治疗方法是癌症的神经系统并发症 不足。 单克隆抗体的发展提供了 对具有反应性的肿瘤进行更特异性治疗的潜力 单克隆抗体或抗体片段。 抗体是 特定于肿瘤细胞并且不与正常大脑或 脊髓可以与治疗性放射性同位素结合，例如 131I. 然后可以将这种结合物鞘内递送 软脑膜肿瘤或进入手术切除腔 为脑肿瘤提供治疗剂量的辐射 对肿瘤细胞的相对特异性。 131I标记81C6单克隆抗体用于患者的II期研究 患有肿瘤性脑膜炎或术后囊性空洞 与 CSF 通信（CRU 协议 753），建立在成功的基础上 完成针对患有以下疾病的患者的 I 期研究 CRU 方案 648 转移至软脑膜的肿瘤。 在第二阶段研究中， 符合条件的患者每月接受 60 mCi 鞘内注射治疗 131I 标记的 81C6 单克隆抗体（10 mg 蛋白质）。患者是 每八周评估一次反应。 响应标准基于 MRI 扫描中脑脊液细胞学和肿瘤大小的客观测量。 为了 对于复发性肿瘤的患者，治疗应持续进行，直至肿瘤消失为止。 12 个周期完全缓解，12 个周期疾病稳定， MRI 或体检记录的进行性或复发性疾病， 4级非血液学毒性或血液学毒性需要 回输患者先前储存的外周干细胞。 初诊肿瘤且无有效常规治疗方法的患者 治疗方法是存在的，例如恶性胶质瘤转移到 软脑膜，治疗 4 个周期，然后转至外部 除非较早发现进展性肿瘤，否则采用束放疗。 新诊断患者治疗时间的其他标准 与复发性肿瘤患者的情况相同。对于每个 5 个组织学亚组，两阶段 II 期设计，区分 10% 到 30% 之间的响应率将用于评估 鞘内 131I 标记的 81C6 的活性。