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

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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.