Radiolabeled Antibody Therapy of B-Cell Lymphoma

B 细胞淋巴瘤的放射性标记抗体治疗

基本信息

批准号：
6913345
负责人：
Ajay Gopal
金额：
$ 18.47万
依托单位：
FRED HUTCHINSON CANCER RESEARCH CENTER
依托单位国家：
美国
项目类别：
财政年份：
2005
资助国家：
美国
起止时间：
2005-05-01 至 2010-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6913345
关键词：
B cell lymphoma antitumor antibody clinical trial phase I clinical trial phase II combination cancer therapy cyclophosphamide drug screening /evaluation etoposide fludarabine human subject human therapy evaluation iodine longitudinal human study monoclonal antibody neoplasm /cancer chemotherapy neoplasm /cancer radioimmunotherapy neoplasm /cancer relapse /recurrence nonHodgkin&apos s lymphoma patient oriented research radionuclides radiopharmacology stem cell transplantation

B cell lymphoma antitumor antibody clinical trial phase I clinical trial phase II combination cancer therapy cyclophosphamide drug screening /evaluation etoposide fludarabine human subject human therapy evaluation iodine longitudinal human study monoclonal antibody neoplasm /cancer chemotherapy neoplasm /cancer radioimmunotherapy neoplasm /cancer relapse /recurrence nonHodgkin&apos s lymphoma patient oriented research radionuclides radiopharmacology stem cell transplantation

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项目摘要

Despite dramatic advances in combination chemoimmunotherapy for newly diagnosed patients with non-Hodgkin's lymphomas (NHL), few patients with relapsed B cell NHL can be cured with conventional treatments. The primary objective of this project is to optimize the therapeutic utility of high dose radiolabeled monoclonal antibodies targeting the CD20 antigen in conjunction with autologous stem cell transplant (ASCT) for treating patients with relapsed or refractory B cell lymphomas. In this application, we propose four approaches to achieve this goal. First, we will conduct a disease-specific, phase II trial of (131)I-anti-CD20 antibody with etoposide (VP16), cyclophosphamide (CY) and ASCT to establish the efficacy of this regimen for treating three of the most common histologic subtypes of relapsed B NHL (Aim I). Second, we will explore the ability of a synergistic chemotherapeutic agent (fludarabine) to enhance the efficacy of (131)I-anti-CD20 antibody for older patients in the setting of ASCT (Aim II). Third, we will investigate the feasibility and safety of improving the specificity of radiation dose delivery to tumor sites using pre-targeting technology (Aim III). Finally, we will perform long-term follow-up of patients treated on prior Phase I & II trials with (131)I-anti-CD20 antibodies + ASCT to ascertain long term efficacy and delayed toxicities (Aim IV). This sequence of studies should enable us to achieve our long term objectives of further establishing and augmenting the role of high dose radioimmunotherapy and ASCT in the treatment of relapsed NHL.

尽管对于新诊断的非霍奇金淋巴瘤（NHL）患者的联合化学免疫疗法的急剧进步，但很少有复发性B细胞NHL患者可以用常规治疗方法治愈。该项目的主要目的是优化针对CD20抗原的高剂量放射性标记单克隆抗体与自体干细胞移植（ASCT）的治疗，以治疗患者复发或耐火性B细胞淋巴瘤。在此应用程序中，我们提出了四种实现此目标的方法。首先，我们将对（131）I-ANTI-CD20抗体（VP16），环磷酰胺（CY）和ASCT进行（131）I-ANTI-CD20抗体，以确立该方案的功效，以治疗三种最常见的治疗Relapsed B NHL的组织学亚型（AIM I）。其次，我们将探讨协同化学治疗剂（Fludarabine）增强功效的能力（131）在ASCT的情况下，老年患者的I-ANTI-CD20抗体（AIM II）。第三，我们将研究使用预靶向技术（AIM III）提高辐射剂量递送到肿瘤部位的特异性的可行性和安全性。最后，我们将对（131）I-ANTI-CD20抗体 + ASCT进行先前I＆II试验治疗的患者进行长期随访，以确定长期疗效和延迟毒性（AIM IV）。这一研究序列应该使我们能够实现进一步建立和增强高剂量放射免疫疗法和ASCT在复发NHL治疗的长期目标。