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

项目摘要 此拨款申请旨在更新我们作为核心临床中心和指导成员的地位 血液和骨髓移植临床试验网络委员会（BMT CTN）。希望之城 造血细胞移植计划在过去的40年里一直致力于发展 基于实验室的转化研究和I、II、III期临床试验， 造血细胞移植（HCT）用于治疗恶性和非恶性血液病 紊乱在我们作为BMT CTN成员的15年中，我们参与了临床 试验集中在HCT患者面临的重要问题，其中一些来自早期阶段 在我们的计划中进行的研究。我们的许多教师都为成功做出了重大贡献。 进行BMT CTN试验，并将继续共同努力，以实现改善 HCT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 能够招募不同的患者并支持多中心HCT试验，包括细胞疗法。 City of Hope长期以来一直专注于巨细胞病毒（CMV）的研究， HCT后并发症，解决了改善目前基于抗病毒药物的 接近。我们的实验室合作者已经开发和制造了CMV疫苗（CMVPepVax） 利用与通用TH表位（天然破伤风抗原）融合的HLA A*0201 pp 65495 -503 CD 8 + T细胞表位 序列），其与CpG佐剂PF-03512676共注射。该疫苗已被证明安全， 在健康志愿者和HCT接受者的Ib期试验中， 减少CMV再活化。CMVPepVax的安慰剂对照随机II期试验目前正在进行中。 正在进行中，进展顺利。作为这项申请的一部分，我们建议BMT CTN与城市合作， 的希望和许可证保持器Helocyte，进行了前瞻性III期随机，双盲，多- 在接受来自匹配的相关或无关供体的HCT的患者中比较CMVPepVax与安慰剂的中心试验。 我们的研究假设是，在HCT后第28天和第56天使用CMVPepVax将改善12个月的CMV- 与安慰剂组相比，疫苗组的自由生存期。

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.