131I HUMAN MONOCLONAL ANTIBODY BT32/A6 IN MALIGNANT GLIOMA

这是一项I期临床试验，评估安全性，药代动力学， 单次IV给药的生物分布和肿瘤定位程度 将131=I放射性标记的人抗神经胶质瘤MAb BT32/A6在 组织学证实的恶性胶质瘤（胶质母细胞瘤）患者 多形性，间变性星形细胞瘤，胶质肉瘤，间变性 少突胶质细胞瘤或混合性间变性胶质瘤）， 持续性或复发性疾病。 患者将接受单次静脉注射 输注约1 mg 131-I标记的MAb BT32/A6（特异性 放射性=约10 mCi/mg抗体）/70 kg IBW 每隔30分钟给药一次。 目的是获得 至少上述4个参数中每一个的可评价数据 6名患者。 超过6名患者可以接受治疗，以达到这一点 目标，但治疗人数不会超过20人。 人单克隆抗体 BT32/A6是识别胶质瘤细胞表面的IgM（k）同种型 在原代人脑胶质瘤和人脑胶质瘤细胞中表达的抗原 线，但在正常成人大脑和其他正常成人大脑中没有 组织中 将对所有患者进行全面的药代动力学分析 在这个I期试验中的患者。 131-I MAb BT32/A6的血清水平将 通过放射性计数程序进行定量。 的分析 将测定血清中放射性标记的MAb BT32/A6的免疫反应性。 将通过全细胞评估血清样本的免疫反应性 （SK-MG-1恶性胶质瘤）结合试验，比较相对% 与加标新鲜标记MAb BT32/A6的对照血清的结合。 药代动力学参数，如半衰期、曲线下面积 (AUC)、平均滞留时间（MRT）、稳态分布容积 将使用以下方法估计和比较VDss和清除率（CL） 动力学分析和建模的标准方法。 将进行相关和回归分析，以检查 药代动力学参数、HAIA和毒性之间的关系。 将进行剂量测定分析，以比较全身剂量和 肿瘤与正常组织的比率。

This is a Phase I clinical trial to assess the safety, pharmacokinetics, biodistribution and extent of tumor localization of a single dose of IV administered 131=I radiolabeled human anti-glioma MAb BT32/A6 in patients with a histologically confirmed malignant glioma (glioblastoma multiforme, anaplastic astrocytoma, gliosarcoma, anaplastic oligodendroglioma or mixed anaplastic glioma) with a measurable persistent or recurrent disease. Patients will receive a single IV infusion of approximately 1 mg of 131-I labeled MAb BT32/A6 (specific radioactivity = approximately 10 mCi/mg of antibody) per 70 kg IBW administered over a 30 minute interval. The objective is to obtain evaluable data for each of the 4 aforementioned parameters on a minimum of 6 patients. More than 6 patients may be treated to attain this objective, but the number treated will not exceed 20. The human MAb BT32/A6 is an IgM(k) isotype that recognizes a glioma cell surface antigen that is expressed in primary human gliomas and human glioma cell lines but not in normal human adult brain and other normal human adult tissues. A full pharmacokinetic analysis will be performed on all patients in this Phase I trial. Serum levels of 131-I MAb BT32/A6 will be quantified by a radiometric counting procedure. Analyses of the immunoreactivity of the radiolabeled MAb BT32/A6 in sera will be made. Serum samples will be assessed for immunoreactivity through a whole cell (SK-MG-1 malignant glioma) binding assay which compares relative % binding to control sera spiked with freshly labeled MAb BT32/A6. Pharmacokinetical parameters such as half-life, area under the curve (AUC), mean residence time (MRT), volume of distribution at steady state (VDss) and clearance rate (CL) will be estimated and compared using standard methods for pharmacokinetical analysis and modeling. Correlation and regression analysis will be conducted to examine the relationships among pharmacokinetical parameters, HAIA and toxicity. Dosimetry analysis will be performed to compare whole body dose and tumor to normal tissue ratios.