BMT Clinical Trial Network at Stanford

描述（由申请人提供）：本提案是根据RFA: HL-11-013提交的，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，包括自体和同种异体移植，有匹配的相关供体，不匹配的相关供体和匹配的非相关供体。清髓移植和非清髓移植均可用于血液系统恶性肿瘤。斯坦福大学的BMT项目以单一机构、联盟、区域肿瘤小组和国家试验的身份参与临床研究，并在确定恶性血液病患者移植的作用和优化移植方面处于领先地位。该项目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项目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发挥作用。到目前为止，斯坦福大学已经积累了141名患者进行了10次CTN试验，斯坦福大学的研究人员担任了三个网络协议的国家主席，并主持了两个CTN委员会。该方案提出的目的是改进T细胞耗竭策略的异体骨髓清除HCT设置患者的血液恶性肿瘤使用匹配的相关供体。我们建议在HCT后将T细胞重新加入，同时以预先设定的剂量和比例输注自然产生的调节性T细胞。假设是这样的操作将改善免疫重建和降低复发风险，但由于调节性T细胞的抑制机制而控制急性GVHD。不进行hct后免疫抑制。斯坦福BMT项目致力于继续参与网络试验，并为小组考虑提供概念。相关性（见说明）：这项拨款的任务是建立一个已建立的干细胞移植中心网络，如斯坦福血液和骨髓移植项目，以合作和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