Radiolabeled Antibody Therapy of B-Cell Lymphoma

B 细胞淋巴瘤的放射性标记抗体治疗

• 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
• 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' s lymphoma; patient oriented research; radionuclides; radiopharmacology; stem cell transplantation

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.

尽管针对新诊断的非霍奇金淋巴瘤 (NHL) 患者的联合化学免疫疗法取得了巨大进展，但很少有复发性 B 细胞 NHL 患者可以通过常规治疗治愈。该项目的主要目标是优化针对 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) 联合治疗复发或难治性 B 细胞淋巴瘤患者的治疗效用。在此应用中，我们提出了四种方法来实现这一目标。首先，我们将进行一项针对 (131)I-抗 CD20 抗体与依托泊苷 (VP16)、环磷酰胺 (CY) 和 ASCT 的疾病特异性 II 期试验，以确定该方案治疗三种最常见组织学疾病的疗效。复发 B NHL 的亚型（目标 I）。其次，我们将探索协同化疗药物（氟达拉滨）增强化疗疗效的能力。 (131)I-抗 CD20 抗体用于 ASCT 中的老年患者（目标 II）。第三，我们将研究利用预靶向技术（目标 III）提高肿瘤部位放射剂量输送特异性的可行性和安全性。最后，我们将对之前接受 (131)I-抗 CD20 抗体 + ASCT 治疗的 I 期和 II 期试验的患者进行长期随访，以确定长期疗效和延迟毒性（目标 IV）。这一系列研究应该使我们能够实现进一步确立和增强高剂量放射免疫疗法和 ASCT 在复发性 NHL 治疗中的作用的长期目标。