BMT Core - MSK

PROJECT SUMMARY/ABSTRACT The mission of the Blood and Marrow Transplant Clinical Trials Network (BMT CTN) is to “evaluate promising therapeutic approaches in multi-institutional clinical trials to improve the outcomes of blood and bone marrow transplantation and other cellular therapies for patients facing life-threatening blood disorders.” Memorial Sloan Kettering Cancer Center (MSK) is an NCl-designated Comprehensive Cancer Center with one of the largest BMT programs in the country. The BMT program at MSK, founded in 1973 and divided into pediatric and adult services, is a FACT-accredited program for both hematopoietic cell transplant (HCT) and immune effector cell (IEC) therapy. MSK has been a Core Clinical Center (CCC) of the BMT CTN since its inception. Dr. Perales (Service Chief, Adult BMT; PI, MSK BMT CTN), Dr. Giralt (Deputy Head, Division of Hematologic Oncology; Co- I), Dr. Boelens (Service Chief, Pediatric BMT and Cell Therapy; Co-I), and all members of the Adult and Pediatric BMT and Cellular Therapy Services consider participation in the BMT CTN an integral part of their mission. In this proposal, we detail our ongoing commitment to the success of the Network through an oversight structure that includes a BMT CTN MSK Executive Committee, a BMT CTN Protocol Management Team, and a BMT CTN Internal Advisory Board, which leverage senior leadership of the Division of Hematologic Oncology and Pediatric BMT Service as well as outstanding scientists and investigators at MSK. As part of our continued commitment to Network leadership, we propose a multicenter phase II clinical trial in adults and children with severe sickle cell disease (SCD), in which we will evaluate a pharmacologic immunosuppressive strategy prior to reduced toxicity myeloablative mismatched unrelated (MMUD) HCT, using post-transplant cyclophosphamide (PTCY)- based graft-versus-host disease (GvHD) prophylaxis. The trial will employ a novel platform to mitigate the risk of graft failure in a patient population at high risk for allograft rejection and treatment-related complications, as well as pharmacokinetic-based models to guide individualized dosing of fludarabine, busulfan, and rabbit ATG for optimal drug exposure. We propose 3 specific aims: (1) Demonstrate MSK has the clinical and translational expertise, novel cell and gene therapy capabilities, and early- and late-phase trial experience to fulfill the obligations of a BMT CTN CCC and advance the Network’s mission and goals; (2) Complete a phase II study in which patients with severe SCD will receive an HCT from an MMUD donor with PTCY-based GvHD prophylaxis (the primary endpoint will be to estimate primary graft failure at 1-year post-HCT); and (3) Describe how MSK’s operational and scientific approaches to conducting HCT trials will support the mission and activities of the BMT CTN. The proposed study is highly relevant to the BMT CTN, as it addresses an unmet need for a well-tolerated alternative donor platform with stable engraftment in patients with SCD, and is in line with the goal of the BMT CTN to prioritize clinical studies that advance HCT approaches for non-malignant blood diseases.