Radiolabeled Antibody Therapy of B-Cell Lymphoma

尽管新诊断的非霍奇金淋巴瘤（NHL）患者在联合化疗免疫治疗方面取得了巨大进展，但很少有复发的B细胞NHL患者可以通过常规治疗治愈。该项目的主要目的是优化靶向CD20抗原的高剂量放射标记单克隆抗体结合自体干细胞移植（ASCT）治疗复发或难治性B细胞淋巴瘤患者的治疗效果。在这个应用程序中，我们提出了四种方法来实现这一目标。首先，我们将对（131）I抗cd20抗体与依托泊苷（VP16）、环磷酰胺（CY）和ASCT进行一项疾病特异性II期试验，以确定该方案治疗三种最常见的复发性B型NHL （Aim I）的组织学亚型的疗效。其次，我们将探索一种协同化疗药物（氟达拉滨）的能力，以提高疗效

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.