131I HUMAN MONOCLONAL ANTIBODY BT32/A6 IN MALIGNANT GLIOMA

131I 人类单克隆抗体 BT32/A6 在恶性胶质瘤中的应用

• 批准号: 6244039
• 负责人: STEVEN S ROSENFELD
• 金额: $ 2.46万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-02-10 至 1997-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6244039
• 关键词: antineoplastics; clearance rate; clinical research; clinical trial phase I; drug screening /evaluation; glioma; human subject; human therapy evaluation; immunoglobulin M; intravenous administration; iodine; monoclonal antibody; neoplasm /cancer chemotherapy; neoplasm /cancer immunotherapy; pharmacokinetics; radiation dosage; radionuclides; surface antigens

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.

这是一项I期临床试验，以评估安全性、药动学、 单次静脉注射的生物分布和肿瘤定位范围 ~(131)I标记人源性抗胶质瘤单抗BT32/A6体内给药 经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 少突胶质瘤或混合性间变性胶质瘤) 顽固性或复发性疾病。患者将接受一次静脉注射 输注约1毫克131-I标记的单抗BT32/A6(特异性 放射性=每70公斤IBW约10微克/毫克抗体) 每隔30分钟服用一次。其目的是为了获得 上述4个参数中每一个的可评估数据最少 6例。超过6名患者可能需要接受治疗才能做到这一点。 客观，但治疗人数不会超过20人。人源单抗 BT32/A6是一种识别胶质瘤细胞表面的IgM(K)亚型 在原发人脑胶质瘤和人脑胶质瘤细胞中表达的抗原 但在正常成人脑和其他正常成人脑中不存在 纸巾。将对所有患者进行全面的药代动力学分析 这项I期试验的患者。血清131-I单抗BT32/A6水平将 通过辐射计数程序进行量化。对网络安全问题的分析 将标记的单抗BT32/A6在血清中进行免疫反应。 血清样本将通过整个细胞进行免疫反应评估。 (SK-MG-1恶性胶质瘤)结合试验比较相对百分率 结合到用新标记的单抗BT32/A6添加的对照血清。 药动学参数，如半衰期、曲线下面积 (AUC)、平均停留时间(MRT)、稳态分布体积 (VDSS)和清扫率(CL)将被估计和比较，使用 药代动力学分析和建模的标准方法。 将进行相关和回归分析，以检验 药代动力学参数、血药浓度和毒性之间的关系。 将进行剂量分析，以比较全身剂量和 肿瘤与正常组织的比率。