University of Michigan Core Clinical Center for BMT Research Network

密歇根大学 BMT 研究网络核心临床中心

• 批准号: 9069014
• 负责人: GREGORY A YANIK
• 金额: $ 16.09万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-30 至 2017-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9069014
• 关键词: Acute Graft Versus Host Disease; Allogenic; Antithymoglobulin; Biological Markers; Clinical; Clinical Trials; Data; Dose; Enrollment; Etanercept; Functional disorder; Grant; Hematopoietic Stem Cell Transplantation; Instruction; Michigan; Morbidity - disease rate; Multi-Institutional Clinical Trial; PI3 gene; Patient-Focused Outcomes; Patients; Pentostatin; Phase II Clinical Trials; Plasma; Prophylactic treatment; Protocols documentation; Randomized; Regimen; Research; Sampling; Science; Seminal; Source; Steroids; Translations; Transplant Recipients; Transplantation; Universities; biomarker panel; graft vs host disease; member; mortality; novel; novel strategies; phase II trial; programs; prophylactic; success; symposium; trial comparing

DESCRIPTION (provided by applicant): Acute graft versus host disease (GHVD) remains a major source of morbidity and transplant-related mortality (TRM) after allogeneic hematopoietic stem cell transplantation (HCT). Despite advances in GVHD prophylactic regimen, significant (grade II-IV) acute GVHD that requires systemic treatment with high dose steroids occurs in 50-70% of HCT recipients of transplants from HLA-matched unrelated donor or partially HLA-matched donors. Outcomes for patients developing acute GVHD remain poor and new prophylactic strategies are needed. The University of Michigan BMT program has made seminal contributions to the understanding of GVHD pathophysiology and to the translation of promising new approaches into clinical trials. The University of Michigan was chosen to be a charter member of the BMT CTN at its inception ten years ago, and it has made key contributions to the success of the network, including a chairmanship of the steering committee, chairmanships of two protocols, additional memberships in six protocols, and the organization and hosting of the highly successful State of the Science Symposium in 2007. This application proposes, in specific Aim I, the comparison of two novel GVHD prophylaxis-required (etanercept vs pentostatin/ATG) in a multicenter, randomized Phase II protocol, the preliminary data for which having been generated at the University of Michigan and MD Anderson. Specific Aim 2 proposes to validate a four biomarker panel (IL2Rd, TNFRI, Elafin and Reg3a) for its ability to predict the onset of GVHD from plasma samples taken early after transplant from patients participating in the proposed trial. If validated, this biomarker panel could be used in subsequent BMT CTN trials to guide the preemptive treatment of acute GVHD. RELEVANCE (See instructions): This grant will make the University of Michigan a Core Center for the BMT CTN in order to conduct multi- center clinical trials in BMT patients.

描述（由申请人提供）：急性移植物抗宿主病（GHVD）仍然是同种异体造血干细胞移植（HCT）后发病率和移植相关死亡率（TRM）的主要来源。尽管GVHD预防方案取得了进展，但在hla匹配的非相关供体或部分hla匹配供体移植的HCT受者中，50-70%发生严重（II-IV级）急性GVHD，需要用大剂量类固醇进行全身治疗。急性GVHD患者的预后仍然很差，需要新的预防策略。密歇根大学的BMT项目为理解GVHD的病理生理学和将有前途的新方法转化为临床试验做出了开创性的贡献。密歇根大学在十年前成立时被选为BMT CTN的创始成员，并为该网络的成功做出了关键贡献，包括担任指导委员会主席，担任两项协议的主席，担任六项协议的其他成员，以及组织和主办了非常成功的2007年科学状况研讨会。本申请提出，在特定的Aim I中，在多中心随机II期方案中比较两种新的GVHD预防所需药物（依那西普与戊司他汀/ATG），其初步数据已在密歇根大学和MD安德森产生。Specific Aim 2建议验证四种生物标志物（IL2Rd、TNFRI、Elafin和Reg3a）在移植后早期从参与拟议试验的患者身上采集的血浆样本中预测GVHD发病的能力。如果得到验证，该生物标志物组可用于后续的BMT CTN试验，以指导急性GVHD的先发制人治疗。相关性（见说明）：这笔拨款将使密歇根大学成为BMT CTN的核心中心，以便在BMT患者中进行多中心临床试验。