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

项目概要 该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 (BMT CTN) 委员会。希望之城 造血细胞移植计划在过去 40 年里致力于开发 基于实验室的转化研究和 I、II 和 III 期临床试验，从而改善 造血细胞移植（HCT）用于治疗恶性和非恶性血液病 失调。作为 BMT CTN 成员的 15 年里，我们参与了临床的开发 试验重点关注 HCT 患者面临的重要问题，其中一些问题源自早期阶段 我们的计划中进行的研究。我们的许多教员为我们的成功做出了重大贡献 进行 BMT CTN 试验，并将继续共同努力，以实现改进的共同目标 HCT 的结果。作为加州最大、历史最悠久的 HCT 中心，我们提供独特且高素质的服务 能够吸引不同的患者并支持多中心 HCT 试验，包括细胞疗法。 City of Hope 长期研究巨细胞病毒 (CMV)，这是最重要的传染病 HCT 后的并发症，解决未满足的需求，以改善当前基于抗病毒药物的短缺 接近。我们的实验室合作者开发并制造了 CMV 疫苗 (CMVPepVax) 利用 HLA A*0201 pp65495-503 CD8 T 细胞表位与通用 TH 表位（天然破伤风 序列）与 CpG 佐剂 PF-03512676 共同注射。该疫苗已被证明安全且 在健康志愿者和 HCT 接受者的 Ib 期试验中显示出免疫原性，在 减少 CMV 重新激活。 CMVPepVax 的安慰剂对照随机 II 期试验目前正在进行 正在进行中并且积累良好。作为本申请的一部分，我们建议 BMT CTN 与市政府合作 Hope 和许可证持有者 Helillary 进行了一项前瞻性 III 期随机、双盲、多 在接受匹配相关或无关捐赠者 HCT 的患者中进行 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 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.