INTRATHECAL MONOCLONAL ANTIBODY FRAGMENT MEL-14 F(AB')2 IN LEPTOMENINGEAL TUMORS

鞘内单克隆抗体片段 MEL-14 F(AB)2 在软脑膜肿瘤中的应用

• 批准号: 6243939
• 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/6243939
• 关键词: brain neoplasms; clinical research; clinical trial phase I; dosage; drug administration routes; human subject; human therapy evaluation; immunoconjugates; iodine; melanoma; meningioma; monoclonal antibody; neoplasm /cancer immunotherapy; neoplasm /cancer radionuclide therapy; radiation therapy dosage; radionuclides

Phase I: This protocol contains two components, each assigned a separate Duke IRB number. The first component utilizes 131Iodine-labeled Me1-14 F(ab')2 monoclonal antibody fragment in the treatment of patients with neoplasms metastatic to the leptomeninges. The purpose of this study is to determine the safety and maximum tolerated dose of intrathecal 131I- labeled Me1-14 F(ab')2 monoclonal antibody fragment in patients with neoplasms metastatic to the leptomeninges. The development of monoclonal antibodies has provided the potential for more specific therapy of tumors growing in the subarachnoid spaces. 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 once intrathecally to deliver a therapeutic dose of radiation with relative specificity for the tumor cells. This is one such protocol, utilizing Me1-14 F(ab')2 fragments conjugated to 131I in the treatment of melanoma metastatic to the leptomeninges. It is a phase I dose-escalation study that is designed to determine the toxicity profile and maximum tolerated dose. The protocol begins at 40 mCi 131I and escalates in 20 mCi increments (i.e., 60, 80, 100, etc. mCi) in cohorts of 3-6 patients per dose level until the maximum tolerated dose is reached. Response will be assessed secondarily. The second component utilizes 131I-labeled Me1-14 F(ab')2 monoclonal antibody fragment in the treatment of patients with primary or metastatic malignant melanoma and other brain tumors with surgically created cystic resection cavities. The purpose of this study is to determine the safety and maximum tolerated dose of 131I-labeled Me1-14 F(ab')2 monoclonal antibody fragment administered into surgically created cystic tumor resection cavities in patients with primary or metastatic malignant melanoma and other brain tumors. he development of monoclonal antibodies has provided the potential for more specific therapy of primary or metastatic brain tumors. 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 once into a surgically- created cystic resection cavity to deliver a therapeutic dose of radiation with relative specificity for the tumor cells. In the other part of this protocol, Me1-14 F(ab')2 fragments conjugated to 131I are utilized in the treatment of patients with primary or metastatic malignant melanoma and other brain tumors with surgically created cystic resection cavities. This is a phase I dose-escalation study designed to determine the toxicity profile and maximum tolerated isotope dosage for these patients. The protocol begins at 40 mCi 131I and escalates in 20 mCi increments (i.e. 60, 80, 100, etc. mCi) in cohorts of 3-6 patients per dosage level until the maximum tolerated dosage is reached. Response is assessed secondarily. 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. Radiolabeled monoclonal antibodies may be a significant new therapeutic modality for these disease entities.

阶段1：该协议包含两个组件，每个组件分配一个单独的