Radioimmunotherapy for Lymphoma

淋巴瘤的放射免疫治疗

• 批准号: 8546158
• 负责人: Ajay Gopal
• 金额: $ 25.63万
• 依托单位: FRED HUTCHINSON CANCER RESEARCH CENTER
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8546158
• 关键词: Address; Adopted; American; Antibodies; Autologous Stem Cell Transplantation; B-Lymphocytes; Biodistribution; CD45 Antigens; Clinical Trials Design; Development Plans; Disease; Disease remission; Disease-Free Survival; Disorder by Site; Dose; Evaluation; Exposure to; Hematopoietic; Indium-111; Intravenous; Ionizing radiation; Lymphoma; MS4A1 gene; Maximum Tolerated Dose; Minority; Monoclonal Antibodies; Newly Diagnosed; Non-Hodgkin' s Lymphoma; Organ; PTPRC gene; Patients; Phase I Clinical Trials; Positron-Emission Tomography; Prior Therapy; Proteins; Radiation; Radiation therapy; Radioimmunoconjugate; Radioimmunotherapy; Radioisotopes; Radiolabeled; Refractory; Regimen; Relapse; Role; Site; T-Cell Lymphoma; Therapeutic; Toxic effect; Transplantation; Whole-Body Irradiation; Work; base; chemoradiation; chemotherapy; conditioning; dosimetry; expectation; improved; innovation; leukemia/lymphoma; radiotracer; response; rituximab; success; tumor

Despite impressive advances in combination chemoimmunotherapy, the majority of newly diagnosed patients with non-Hodgkin lymphomas (NHL) will relapse, and once this occurs only a minority can be cured with current treatments. The primary objective of this project is to develop and optimize an innovative strategy using high-dose radiolabeled monoclonal antibodies targeting the pan-hematopoietic antigen, CD45 in conjunction with autologous stem cell transplantation (ASCT) for patients with relapsed or refractory B or T-cell lymphomas. This approach possesses several advantages. It circumvents potential blocking of CD20 sites by rituximab, amplifies radiation exposure to sites of minimal disease, and allows treatment of CD20-negative lymphomas as well as CD20-expressing lymphomas with a safe, exportable, therapeutic radionuclide, [90]Y. Four Aims are proposed within the context of a phase I clinical trial designed to identify the maximally tolerated dose (MTD) of [90]Y-BC8 that can be delivered prior to ASCT. First, the optimal antibody protein dose of BCS will be determined to assure that a majority of patients achieve higher radiation exposures in tumor sites than in critical normal organs (Aim 1). Second, direct comparisons of the ability of CD45 and CD20 antibodies to target tumor sites will be obtained to confirm the benefit of this strategy in patients with B-NHL (Aim 2). Third, the critical dosimetry question regarding the ability of [111]In to predict [90]Y biodistribution will be addressed by means of [86]Y PET imaging (Aim 3). Following these dosimetry studies, all patients will be treated with [90]Y-BC8 in order to estimate the MTD of this therapy prior to ASCT (Aim 4). This comprehensive development plan should enable the successful evaluation of this innovative therapeutic strategy and achieve the 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的组合进展令人印象深刻，但大多数新诊断 非霍奇金淋巴瘤（NHL）的患者将复发，一旦发生这种情况，只有少数才能是 用当前的治疗方法治愈。该项目的主要目的是开发和优化 使用大剂量放射性标记的单克隆抗体的创新策略，旨在泛滥 抗原，CD45与复发或复发的患者的自体干细胞移植（ASCT）结合 难治性B或T细胞淋巴瘤。这种方法具有几个优势。它规避潜力 利妥昔单抗阻止CD20部位，扩大辐射暴露于最小疾病的部位，并允许 CD20阴性淋巴瘤以及表达CD20的淋巴瘤，具有安全，可导出的 治疗性放射性核素，[90] y。在设计I期临床试验的背景下提出了四个目标 确定可以在ASCT之前传递的[90] Y-BC8的最大耐受剂量（MTD）。首先， 最佳抗体蛋白剂量的BC将确保确保大多数患者获得更高 肿瘤部位的辐射暴露于关键正常器官（AIM 1）。第二，直接比较的 将获得CD45和CD20抗体靶向肿瘤部位的能力，以确认这一点的好处 B-NHL患者的策略（AIM 2）。第三，关于[111]在TO的能力的关键剂量学问题 预测[90] y生物分布将通过[86] y PET成像（AIM 3）来解决。遵循这些 剂量学研究，所有患者将接受[90] Y-BC8治疗，以估算此疗法的MTD 到ASCT（AIM 4）。这项全面的发展计划应能够成功评估 创新的治疗策略，并实现进一步建立和增强的长期目标 高剂量的放射免疫疗法和ASCT在复发NHL治疗中的作用。