Core Clinical Centers for the Blood and Marrow Transplant Clinical Trials Network (UG1)

血液和骨髓移植临床试验网络（BMT CTN）的长期目标是 多中心II期和III期试验的疗效和安全性数据，并推进 免疫和造血细胞疗法，用于治疗血液疾病。莫菲特癌症中心在 将所有用于促进和提供免疫和造血细胞疗法的基础设施， 强大的免疫学工作组适当定位，以设计解决方案，符合GMP的细胞疗法 细胞制造和质量控制设施，BMT和免疫及细胞治疗服务， 为患有非恶性血液疾病的患者提供已建立的和实验性的细胞疗法， 血液恶性肿瘤和实体瘤。我们的团队渴望通过以下方式推动该领域的发展： 与BMT CTN合作进行创新细胞疗法的所有开发步骤。具体目标1是 与BMT CTN合作设计和开展多中心研究，并传播 结果新颖的想法始于一个中心的研究团队，但医学领域的重大进展 治疗需要多中心III期随机试验。我们的团队带来了细胞免疫疗法的专业知识， GVHD免疫生物学和行为学研究。莫菲特癌症中心拥有完善的临床和 转化研究计划，具有不断增长的基础设施，以促进超过40种细胞疗法治疗， 每年有超过400例HSCT，并将继续为我们机构的患者提供BMT CTN试验。我们 带来独特的科学，临床试验设计经验，临床专业知识和数量，以及我们的承诺， 通过极具价值的BMT CTN网络积极追求这些进步。具体目标2是测试 BMT CTN在一项III期多中心试验中评估乌司奴单抗预防GVHD的疗效。BMT第 研究计划已经认识到Th 17与Th 1细胞一起是GVHD中的重要效应子， p40亚基与IL-12和IL-23共享，与GVHD相关 发病机制我们目前的初步数据来自一项安慰剂对照的原则性临床试验， ustekinumab（StelaraTM）是一种抗人p40的抗体，可将T细胞极化为Th 2，同时抑制Th 1 Th 17的表达。临床数据还表明，乌司奴单抗有可能减轻 急性和慢性GVHD，并在不破坏移植物抗白血病反应的情况下提高存活率。我们 一项明确的多中心试验的拟议概念解决了预防急性和 慢性GVHD，积极的结果将对未来的临床研究产生持续的，强大的影响， GVHD的预防和扩大异基因造血干细胞移植的应用。

The long term goal of the Blood and Marrow Transplant Clinical Trial Network (BMT CTN) is to generate efficacy and safety data from multicenter Phase II and III trials, and advance the science and technology of immune and hematopoietic cellular therapies for the cure of blood disorders. The Moffitt Cancer Center has in place all the infrastructures for promoting and delivering immune and hematopoietic cellular therapies, with a robust Immunology Working Group properly positioned to design solutions, a GMP-compliant Cellular Therapy Facility for cell manufacturing and quality control, the BMT and the Immune and Cellular Therapy services to deliver established and experimental cellular therapies to patients with nonmalignant blood disorders, hematological malignancies and solid tumors. Our team is eager to contributing moving the field forward by collaborating with the BMT CTN for all the development steps of innovative cellular therapies. Specific Aim 1 is to collaborate with the BMT CTN in the design and conduct of multicenter studies and the dissemination of the results. Novel ideas start from teams of investigators at a single center, but significant advances in medical care require multicenter phase III randomized trials. Our team brings expertise in cellular immunotherapy, GVHD immunobiology, and behavioral studies. Moffitt Cancer Center has a fully established clinical and translational research program with a growing infrastructure to facilitate over 40 cellular therapy treatments and over 400 HSCT per year, and will continue to make BMT CTN trials available to patients in our institution. We bring unique science, clinical trial design experience, clinical expertise and volume, and our commitment to aggressively pursue these advances through the highly valuable BMT CTN network. Specific Aim 2 is to test the efficacy of ustekinumab for GVHD prophylaxis in a phase III multicenter trial by the BMT CTN. The BMT research program has recognized that Th17 are important effectors in GVHD alongside Th1 cells both in rodents and human transplants, and that the p40 subunit shared with IL-12 and IL-23 is relevant to GVHD pathogenesis. We present preliminary data from a placebo-controlled proof-of-principle clinical trial that ustekinumab (StelaraTM), an antibody against the human p40, polarizes T cells to Th2 while dampening Th1 and Th17 after allogenic HSCT. The clinical data also suggest that ustekinumab has the potential for mitigating both acute and chronic GVHD, and improving survival without disrupting graft-vs-leukemia responses. Our proposed concept for a definitive multicenter trial addresses the significant unmet need to prevent acute and chronic GVHD, and positive results will exert a sustained, powerful influence on the future clinical research in GVHD prevention and expand utilization of allogeneic HSCT.