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.

尽管联合化学免疫疗法在新诊断的非霍奇金淋巴瘤（NHL）患者中取得了巨大进展，但很少有复发性B细胞NHL患者可以用常规治疗治愈。本项目的主要目的是优化靶向CD 20抗原的高剂量放射性标记单克隆抗体联合自体干细胞移植（ASCT）治疗复发性或难治性B细胞淋巴瘤患者的治疗效用。在本应用程序中，我们提出了四种方法来实现这一目标。首先，我们将进行一项疾病特异性的II期试验，研究（131）I-抗CD 20抗体与依托泊苷（VP 16）、环磷酰胺（CY）和ASCT联合治疗复发性B NHL（Aim I）的三种最常见组织学亚型的疗效。其次，我们将探索协同化疗剂（氟达拉滨）增强化疗疗效的能力。 （131）I-抗CD 20抗体用于ASCT背景下的老年患者（Aim II）。第三，我们将研究使用预靶向技术（Aim III）提高肿瘤部位放射剂量递送特异性的可行性和安全性。最后，我们将对既往I期和II期试验中接受（131）I-抗CD 20抗体+ ASCT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）。这一系列的研究应该使我们能够实现我们的长期目标，进一步建立和加强高剂量放射免疫治疗和ASCT在治疗复发性NHL中的作用。