BMT Clinical Trial Network at Stanford

描述（由申请人提供）：本提案是为了响应RFA：HL-11-013而提交的，旨在提议将斯坦福大学血液和骨髓移植（BMT）项目作为血液和骨髓临床试验网络的核心临床中心。斯坦福大学的BMT项目每年进行约250例成人移植和约20例儿科移植，包括匹配相关、不匹配相关和匹配无关供体的自体和同种异体手术。清髓性和非清髓性移植均用于恶性血液病。斯坦福大学的BMT项目作为一个单一的机构、联盟、区域肿瘤学小组和国家试验参与临床研究，并一直是确定血液恶性肿瘤患者的作用和优化移植的领导者。该计划拥有经验丰富的数据管理团队和GMP认证的干细胞处理实验室。斯坦福大学BMT计划是当前网络活动的积极参与者，并作为特许核心中心之一在高水平上表现出色。迄今为止，斯坦福大学已经为10项CTN试验招募了141名患者，斯坦福大学的研究人员担任了三项网络协议的国家主席，并主持了两个CTN委员会。提出的方案旨在改进使用匹配的相关供体在血液恶性肿瘤患者中进行同种异体清髓性HCT时的T细胞耗竭策略。我们建议在HCT后T细胞回加，同时以预定的剂量和比例输注天然存在的调节性T细胞。假设这种策略将改善免疫重建并降低复发风险，但由于调节性T细胞的抑制机制而控制急性GVHD。将不给予HCT后免疫抑制。斯坦福大学BMT项目致力于继续参与网络试验，并提出概念供小组审议。相关性（参见说明）：这笔赠款的使命是形成一个由斯坦福大学血液和骨髓移植计划等已建立的干细胞移植中心组成的网络，以合作并进行多中心临床试验。这些临床试验的共同目标是治愈癌症，如白血病、淋巴瘤、骨髓瘤和一些非恶性疾病，如镰状细胞病和再生障碍性贫血。一些临床试验还旨在减少干细胞移植的副作用和毒性作用

DESCRIPTION (provided by applicant): This proposal is submitted in response to RFA: HL-11-013 to propose the Stanford University Blood and Marrow Transplant (BMT) Program as a Core Clinical Center for the Blood and Marrow Clinical Trials Network. The BMT Program at Stanford University performs ~250 adult transplant and ~ 20 pediatric transplants/ year including autologous and allogeneic procedures with matched related, mismatched related and matched unrelated donors. Both myeloablative and non-myeloablative transplants are performed for hematologic malignancies. The BMT Program at Stanford participates in clinical research as a single institution, consortia, regional oncology group and national trials and has been a leader in defining the role and optimizing transplantation for patients with hematologic malignancies. The Program has a highly experienced data management group and a GMP-certified stem cell processing laboratory. The Stanford BMT program is an active participant in current network activities and has performed at a high level as one of the charter Core Centers. Stanford has accrued 141 patients to date to 10 CTN trials and Stanford investigators have served as national Chairs on three network protocols and chaired two CTN committees. The protocol that is proposed aims to improve upon the strategy of T cell depletion in the allogeneic myeloablative HCT setting in patients with hematologic malignancies using matched related donors. We propose T cell add back after HCT simultaneously with infusion of naturally occurring regulatory T cells in pre-defined doses and ratios. The hypothesis is that such maneuvers will improve immune reconstitution and decrease relapse risk but with control of acute GVHD due to the suppressive mechanisms of the regulatory T cells. No post-HCT immunesuppression will be administered. The Stanford BMT Program is committed to continued participation in network trials as well as contributing concepts for consideration by the group. RELEVANCE (See instructions): The mission of this grant is to form a network of established stem cell transplant centers such as the Stanford Blood and Marrow Transplant Program to collaborate and conduct multicenter clinical trials. The common goal of these clinical trials is to cure cancers such as leukemia, lymphoma, myeloma and some non-malignant diseases such as sickle cell disease and aplastic anemia. Some of the clinical trials also aim to reduce the side effects and toxic effects of stem cell transplantation