BMT Clinical Trial Network at Stanford

这是对RFA-HL-17-018的续展申请，建议血液和骨髓的划分 斯坦福大学的骨髓移植继续成为骨髓移植的核心临床中心 临床试验网络(BMT CTN)。斯坦福大学的项目将进行大约380例成人移植 2016年包括使用匹配细胞和同种异体细胞的自体和异体移植 不匹配的亲属和非亲属捐赠者，脐带血单位，体外操纵的细胞产品 和转基因细胞。斯坦福大学的BMT项目参与基础和临床 作为一个单一机构，在区域、国家和国际联合体内进行研究。这个 该部门得到了美国国立卫生研究院(NIH)项目拨款的支持，该项目的资金超过27 多年来对基础科学研究和临床转化试验的资助，推动了 菲尔德。该计划得到了经验丰富的生物静力学和数据管理的加强 团体，以及符合cGMP、FACT和CLIA认证的常规细胞治疗设施 细胞加工和研究细胞疗法的发展。该计划是一项高水平的 应计骨髓移植CTN中心，已经招募了320名患者参加16项CTN研究。在过去，授予 在此期间，斯坦福大学调查人员担任BMT CTN指导委员会主席，主席 淋巴瘤研讨会委员会，并曾是五个CTN委员会和 一个特遣部队。斯坦福大学将继续利用其项目的能力来支持 CTN的研究目标。推动患者骨髓移植领域的发展是我们的共同使命 通过高质量的多中心临床试验，治疗罕见和难于治疗的血液疾病。这个 在当前应用中提出的协议的目标是确定新的策略是否可以 降低慢性移植物抗宿主病(CGVHD)的风险，从而改善传统 异基因骨髓移植。我们提出了一项随机的3期临床试验，其中活跃的比较对象是 伊布鲁替尼在移植后90天开始，对照组没有额外的cGVHD预防 策略。这项研究建立在我们之前的临床前和临床工作的基础上，该药物用于 慢性移植物抗宿主病的治疗和预防。主要的结果衡量标准是类固醇的比率。 移植后18个月需要cGVHD。根据汇总的数据，我们 假设伊布鲁替尼能够阻断B细胞，从而减少cGVHD的发生 Bruton‘s酪氨酸激酶(BTK)的不可逆抑制激活及其阻断T细胞的能力 通过抑制IL-2诱导的T细胞激酶(ITK)激活辅助性亚群。斯坦福大学的BMT 计划致力于继续参与BMT CTN试验，为 由网络审议，参加网络委员会和公民活动。 好了！

This is a renewal application to RFA-HL-17-018 to propose that Division of Blood and Marrow Transplantation (BMT) at Stanford University continue as a Core Clinical Center for the BMT Clinical Trials Network (BMT CTN). Stanford's Program will perform about 380 adult transplants in 2016 including autologous and allogeneic transplants using cells from matched and mismatched related and unrelated donors, cord blood units, ex vivo manipulated cell products and genetically modified cells. Stanford's BMT Program participates in basic, and clinical research as a single institution, and within regional, national and international consortia. The division is supported by a National Institutes of Health (NIH) Program Project Grant with over 27 years of funding of basic scientific research, and clinical translational trials that advance the field. The Program is strengthened by highly experienced biostatics and data management groups, and a cGMP-compliant, FACT and CLIA certified Cellular Therapy Facility for routine cell processing and the development of investigational cellular therapies. The Program is a high accrual BMT CTN center and has enrolled 320 patients to 16 CTN studies. In the past granting period, Stanford investigators served as Chair of the BMT CTN Steering Committee, Chair to the Lymphoma Symposium Committee, and have been members on five CTN committees and one Task Force. Stanford will continue to leverage the capabilities of its Program to support the research goals of the CTN. It is our collective mission to advance the field of BMT for patients with rare and difficult to treat blood diseases through high quality multi-center clinical trials. The goal of the proposed protocol in the current application is to determine if a novel strategy can reduce the risk of developing chronic GVHD (cGVHD) and thereby improve upon traditional allogeneic BMT. We propose a randomized phase 3 clinical trial where the active comparator is Ibrutinib starting 90 days after transplant and the control arm is no additional cGVHD prevention strategy. This study builds upon our prior preclinical and clinical work with this agent for the treatment and prevention of cGVHD. The primary outcome measure will be the rate of steroid requiring cGVHD by 18 months after transplant. Based on an aggregate of data, we hypothesize that Ibrutinib will reduce cGVHD development due to its ability to block B cell activation via irreversible inhibition of Bruton's tyrosine kinase (BTK) and its ability to block T helper subset activation from inhibition of IL-2 inducible T cell kinase (ITK). The Stanford BMT program is committed to continued participation in BMT CTN trials, contributing concepts for consideration by the Network, and participating in Network committees and citizenship activities. !