City of Hope Core Clinical Center for the Blood and Marrow Transplant Clinical Trials Network

项目总结 这项拨款申请旨在更新我们作为核心临床中心和指导委员会成员的地位 血液和骨髓移植临床试验网络委员会(BMT CTN)。希望之城 在过去的40年里，造血细胞移植计划的重点是发展 以实验室为基础的转化研究和I、II和III期临床试验，从而改善了 造血细胞移植治疗恶性与非恶性血液病 精神错乱。在我们作为BMT CTN成员的15年中，我们参与了临床研究的发展 试验集中在HCT患者面临的重要问题上，其中几个是从早期阶段衍生出来的 在我们的项目中进行的研究。我们的许多教职员工为成功的 进行BMT CTN试验，并将继续集体努力，以实现改进的共同目标 红细胞压积试验的结果。作为加州最大和最古老的HCT中心，我们提供独特和高质量的 能够聚集不同的患者并支持多中心HCT试验，包括细胞疗法。 希望之城长期以来一直致力于巨细胞病毒(CMV)的研究，巨细胞病毒是一种最重要的传染性疾病 HCT后并发症，解决未得到满足的需求，以改善目前以抗病毒药物为基础的短缺 接近了。我们的实验室合作人员已经开发和制造了CMV疫苗(CMVPepVax) 利用融合到通用TH表位(天然破伤风)的HLAA*0201 pp65495-503 CD8 T细胞表位 序列)，与CPG佐剂PF-03512676共注射。这种疫苗已经证明是安全的和 在健康志愿者和HCT接受者的Ib期试验中，免疫原性具有良好的疗效信号 减少CMV的重新激活。CMVPepVax的安慰剂对照随机II期试验目前正在进行 正在进行中，并积累得很好。作为此应用程序的一部分，我们建议BMT CTN与City合作 进行前瞻性的第三阶段随机、双盲、多因素试验。 CMVPepVax与安慰剂在接受匹配的亲属或非亲属捐赠者的HCT患者中的中心试验。 我们的研究假设是，在HCT后第28天和56天使用CMVPepVax将改善12个月的CMV- 与安慰剂组相比，疫苗组的自由存活率更高。

PROJECT SUMMARY This grant application seeks to renew our status as a Core Clinical Center and member of the Steering Committee of the Blood and Marrow Transplant Clinical Trials Network (BMT CTN). The City of Hope Hematopoietic Cell Transplantation Program has focused its efforts over the last 40 years on the development of laboratory-based translational research and Phase I, II and III clinical trials leading to improvements in hematopoietic cell transplantation (HCT) for the treatment of malignant and non-malignant hematologic disorders. During our 15 years as a member of the BMT CTN, we have participated in the development of clinical trials focused on important questions confronting HCT patients, several of which were derived from early phase studies conducted in our program. Many of our faculty members significantly contributed to the successful conduct of the BMT CTN trials and will continue to collectively work toward the common goal of improving outcomes of HCT. As the largest and oldest HCT center in California we offer unique and highly qualified capabilities for accruing diverse patients and supporting multi-center HCT trials, including cellular therapeutics. City of Hope has a longstanding research focus on cytomegalovirus (CMV), the most significant infectious complication post-HCT, addressing the unmet need to improve the current shortfalls of anti-viral drug-based approaches. Our laboratory collaborators have developed and manufactured a CMV vaccine (CMVPepVax) utilizing the HLA A*0201 pp65495-503 CD8+ T cell epitope fused to a universal TH epitope (a natural Tetanus sequence) that is co-injected with the CpG adjuvant PF-03512676. This vaccine has demonstrated safety and immunogenicity in a phase Ib trial of healthy volunteers and in HCT recipients, with promising efficacy signals in reducing CMV reactivation. The placebo-controlled randomized phase II trial of CMVPepVax is currently underway and accruing well. As part of this application we propose that the BMT CTN, in collaboration with City of Hope and the license holder Helocyte, conducts a prospective Phase III randomized, double-blind, multi- center trial of CMVPepVax versus placebo in patients receiving HCT from matched related or unrelated donors. Our study hypothesis is that use of CMVPepVax on days 28 and 56 post-HCT will improve the 12-month CMV- free survival in the vaccine arm compared to the placebo arm.