Core Clinical Consortium for Blood and Marrow Transplant Clinical Trials Network

摘要 为了解决造血细胞移植（HCT）患者，特别是异基因HCT， 患者，进入临床试验，探索改善结果的策略，NHLBI和NCI特许血液 骨髓临床试验网络（BMT CTN）。本申请的目的1提出了继续 UF联盟的参与，由佛罗里达大学（UF）和埃默里大学（欧盟）组成，作为一个 BMT CTN的核心联合体，继续参与多项正在进行的试验和待实施的试验 在下一个融资周期中。UF联盟每年进行>600次HCT。UF联盟一直是一个 自2001年BMT CTN成立以来，我们一直是一个高效的核心中心， 达到或超过所有年度BMT CTN性能标准。UF联盟参加了41个 在42项BMT CTN试验中，一直超过年度目标入组，一直处于核心试验的前25%。 在当前的资助周期内，中心/联盟的注册人数增加了一倍，BMT CTN的注册人数增加了一倍 在上一个供资周期进行的审判。Wingard和Waller和其他UF财团调查人员 提供了强有力的科学领导，撰写了25篇出版物（4篇为第一作者，3篇为资深作者）， 14个方案委员会（2名PI）、6个终点审查委员会和7个行政和技术委员会 委员会（担任3个委员会的主席）。两人都曾在美国国立卫生研究院科学研讨会的领导角色。 数据报告错误率远低于BMT CTN研究的目标错误率（2.0%或更低）。 同样，报告的及时性也超过了CTN的接受标准。UF Consortium的优势 这个核心将能够继续扩大其对BMT CTN试验的应计费用。UF的独特优势 财团带来的下一个周期的资金是获得大量的镰状细胞病（SCD）患者， 每个HCT团队与SCD合作者，经验丰富的免疫重建实验室， 树突状细胞生产和其他新的细胞疗法生产能力，在这两个地点，多个 两个研究中心正在进行的细胞疫苗/HCT试验。 本申请的目标2提出了一种协议概念，以解决所识别的2个高优先级研究主题 在国家科学研讨会：移植物抗宿主病（GVHD）和感染。多样性的改变 同种异体HCT后肠道微生物群的变化与严重感染、GVHD、治疗- 相关死亡率、肺部并发症和复发。吲哚化合物，由肠道产生 微生物群，具有免疫调节特性。我们进行的小鼠初步研究表明， 益生元，以降低GVHD的风险，同时保持移植物抗白血病的效果。在本申请中，我们 我建议测试吲哚益生元干预，以防止GVHD和严重感染，首先在一个随机 2期试验，以评估在多中心设置的可行性，然后在3期随机试验。这种新方法 预防GVHD为避免当前免疫抑制方案的毒性提供了前景。

Abstract To address the concern that few hematopoietic cell transplant (HCT) patients, especially allogeneic HCT patients, enter clinical trials to explore strategies to improve outcomes, the NHLBI and NCI chartered the Blood and Marrow Clinical Trials Network (BMT CTN) in 2001. Aim 1of this application proposes continuation of participation of the UF Consortium, consisting of the University of Florida (UF) and Emory University (EU), as a core consortium of the BMT CTN for continued participation in multiple ongoing trials and trials to be implemented in the next funding cycle. The UF Consortium performs >600 HCTs annually. The UF Consortium has been a highly effective core center since the BMT CTN's inception in 2001 with a proven track record of consistently meeting or exceeding all annual BMT CTN performance standards. The UF Consortium has participated in 41 of 42 BMT CTN trials, has consistently exceeded annual target enrollments, has been in the top 25% of core centers/consortia in enrollment during the current funding cycle, and has doubled its enrollments to BMT CTN trials during the past funding cycle. Drs. Wingard and Waller and other UF consortium investigators have provided strong scientific leadership, authoring 25 publications (4 as first author and 3 as senior author), serving on 14 Protocol Committees (2 as PI), 6 Endpoint Review Committees, and 7 Administrative and Technical Committees (serving as chair of 3). Both have served in leadership roles in the NIH State of Science Symposia. Data reporting error rates have been well below the targeted error rate for the BMT CTN studies (2.0 % or lower). Similarly, timeliness of reports has exceeded CTN acceptance standards. The advantage of the UF Consortium is that this core will be able to continue to expand its accrual to BMT CTN trials. Unique strengths the UF Consortium brings to this next cycle of funding is access to large numbers of Sickle Cell Disease (SCD) patients, robust interactions of each HCT team with SCD collaborators, an experienced immune reconstitution laboratory, dendritic cell manufacturing and other novel cell therapy manufacturing capacity at both sites with multiple ongoing cell vaccine/HCT trials at both sites. Aim 2 of this application proposes a protocol concept to address 2 high priority research topics identified in the States of Science Symposia: graft versus host disease (GVHD) and infection. Alterations in the diversity of the gut microbiota after allogeneic HCT are associated with risks for serious infections, GVHD, treatment- related mortality, pulmonary complications and relapse. Indole compounds, produced by the intestinal microbiota, have immunoregulatory properties. Pilot murine studies by us indicate the ability of an indole prebiotic to reduce the risk for GVHD while preserving graft versus leukemia effects. In this application we propose to test an indole prebiotic intervention to prevent GVHD and serious infection, first in a randomized phase 2 trial to assess feasibility in a multicenter setting, then in a phase 3 randomized trial. This novel approach to prevent GVHD offers the prospect to avoid toxicities of current immunosuppressive regimens.