MONOCLONAL ANTIBODY 81C6-I-131 METASTATIC TO LEPTOMENINGES

该协议包含两个活动组件，每个组件都分配了一个单独的 Duke IRB编号，以及第三个组件，已成功 已完成，现已关闭。已完成的组件 应用~(131)I标记的81C6单抗治疗卵巢癌 肿瘤转移至软脑膜的患者。目的 本研究旨在确定阿司匹林的安全性和最大耐受量 鞘内~(131)I标记的81C6单抗在慢性病患者中的应用 转移到软脑膜的肿瘤。在这其中的一部分 方案：采用结合~(131)I的81C6-IgG单抗 在治疗转移到软脑膜的肿瘤中 术后与脑脊液相通的肿瘤囊性腔 流体。这是一项I期剂量递增研究，旨在确定 毒性分布和最大耐受同位素剂量。礼仪开始了 在40 MCI 131I，并且以20 MCI增量(即，60，80,100， 等MCI)在每个剂量水平3-6名患者的队列中，直到最大 已达到耐受量。对疗效进行二次评定。这个 单次鞘内注射131I-81C6的最大耐受量 成年患者给予80mCI 131I-81C6(10 mg蛋白质)。 剂量限制性毒性为血液学毒性。我们治疗了31人 13例患者中有1例出现部分缓解和病情稳定 31例(42%)。协议的这一部分已经取得了成功。 已经完成，并出版了描述结果的手稿 (见所附副本)。该协议的一个有效组件利用 ~(131)I标记81C6单抗治疗慢性粒细胞白血病 原发或转移性恶性脑肿瘤 囊性切除空洞。这项研究的目的是确定 ~(131)I标记81C6单抗的安全性和最大耐受量 抗体在手术后囊性肿瘤切除术中的应用 原发或转移性恶性脑肿瘤患者的空洞。 第二活性成分利用131I标记的81C6单抗 抗体在治疗复发性囊性胶质瘤中的作用。 这项研究的目的是确定安全和最大限度 ~(131)I标记81C6单抗的耐受量 复发患者进入自然发生的肿瘤囊腔 囊性胶质瘤。结合131I的81C6免疫球蛋白单抗 用于治疗复发性囊性胶质瘤患者或 原发或转移性恶性脑肿瘤患者 手术造成的囊性切除空洞。这是第一阶段的剂量- 上报研究旨在确定毒性分布和 以上每个患者群体的最大耐受同位素剂量。这个 协议开始于20 MCI 131I，并以20 MCI为增量升级 (即40、60、80、100等MCI)，每剂量3-6名患者 水平，直到达到最大耐受量。回答是 二次评估。这些研究正在继续增加患者。 我们已确定最大耐受剂量为100 mCI 131I-81C6(20 曾接受过放射治疗的患者的镁蛋白) 囊性切除空洞。协议的这一臂已经关闭，并且一个 手稿正在准备中。现行协议的其他武器 组件仍然开放以进行应计。这些疾病实体都是 癌症存在毁灭性的、无法治愈的神经系统并发症 治疗是不够的。单抗的发展已经 为更特异地治疗肿瘤提供了可能性，这些肿瘤 与所述单抗或抗体片段发生反应。抗体 它们是肿瘤细胞所特有的，不与正常细胞发生反应 大脑或脊髓可以与治疗性放射性同位素结合， 如131I。然后这种结合物可以在鞘内给药 软脑膜肿瘤，进入自然产生的肿瘤囊腔 对于囊性脑瘤，或进入手术创建的切除腔 为实体脑瘤提供治疗量的辐射 对肿瘤细胞的相对特异性。放射性标记的单抗 抗体可能是治疗这些疾病的一种重要的新疗法。 疾病实体。这是美国首次进行的研究 测试这种软脑膜肿瘤和脑的分区治疗 肿瘤切除腔内应用放射性标记的单抗。

This protocol contains two active components, each assigned a separate Duke IRB number, and a third component, which has been successfully completed and is now closed. The component which has been completed utilized 131Iodine-labeled 81C6 monoclonal antibody in the treatment of patients with neoplasms metastatic to the leptomeninges. The purpose of this study was to determine the safety and maximum tolerated dose of intrathecal 131I-labeled 81C6 monoclonal antibody in patients with neoplasms metastatic to the leptomeninges. In one part of this protocol, 81C6 IgG monoclonal antibody conjugated to 131I was utilized in the treatment of neoplasms metastatic to the leptomeninges or postoperative tumor cystic cavities communicating with cerebrospinal fluid. It was a phase I dose-escalation study designed to determine the toxicity profile and maximum tolerated isotope dose. The protocol began at 40 mCi 131I and escalated 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 was reached. Response were assessed secondarily. The maximum tolerated 131I-81C6 dosage for a single intrathecal administration in adult patients was 80 mCi 131I-81C6 (10 mg protein). The dosage limiting toxicity was hematologic toxicity. We treated 31 patients and noted one partial response and disease stabililzation in 13 of 31 patients (42%). This portion of the protocol has been sucessfully completed, and a manuscript describing the results has been published (see attatched copy). One active component of this protocol utilizes 131I-labeled 81C6 monoclonal antibody in the treatment of patients with primary or metastatic malignant 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 81C6 monoclonal antibody administered into surgically created cystic tumor resection cavities in patients with primary or metastatic malignant brain tumors. The second active component utilizes 131I-labeled 81C6 monoclonal antibody in the treatment of patients with recurrent cystic gliomas. The purpose of this study is to determine the safety and maximum tolerated dose of 131I-labeled 81C6 monoclonal antibody administered into naturally occurring tumor cyst cavities in patients with recurrent cystic gliomas. 81C6 IgG monoclonal antibody conjugated to 131I is utilized in the treatment of patients with recurrent cystic gliomas or patients with primary or metastatic malignant brain tumors with surgically created cystic resection cavities. These are phase I dose- escalation studies designed to determine the toxicity profile and maximum tolerated isotope dosage for each patient population above. The protocol began at 20 mCi 131I and is escalating in 20 mCi increments (i.e.40, 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. These studies are continuing to accrue patients. We have identified the maximum tolerated dose as 100 mCi 131I-81C6 (20 mg protein) in previously radiated patients with surgically created cystic resection cavities. This arm of the protocol has closed and a manuscript is in preparation. The other arms of the active protocol components remain open for accrual. These disease entities are all 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, into a naturally-ocurring tumor cyst cavity for cystic brain tumors, or into a surgically-created resection cavity for solid 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. These are the first studies in the United States to test such compartmental therapy of leptomeningeal neoplasms and brain tumor resection cavities with radiolabeled monoclonal antibodies.