Acute GVHD Suppression using Costimulation Blockade to Expand Non-malignant Transplant (ASCENT)
Benjamin Watkins, MD
BACKGROUND: Unrelated donor (URD) hematopoietic stem cell transplantation (HSCT) is used to cure children suffering from serious non-malignant hematologic (i.e. blood) diseases (NMHD), but its benefits are limited by graft-versus-host disease (GVHD), a condition that results from immune cells in the transplant reacting against the patient’s body. Most African-Americans and other ethnic minorities are transplanted with grafts from mismatched donors, which carry an increased risk for rejection. GAP: This trial addresses the critical unmet need for successful transplantation in patients with NMHD, through the elimination of GVHD while maintaining engraftment; in this trial, we will continue to evaluate abatacept, a novel, immunosuppressive agent that we have been studying for over a decade (in patients with hematologic malignancies), but now in the setting of HSCT for pediatric NMHD. HYPOTHESIS: We hypothesize that abatacept will prevent GVHD without increasing risk of rejection or of infection, thus significantly improving cure rates for children undergoing URD HSCT for NMHD. METHODS: This trial is a phase 2, multi-center, single arm trial in which all patients will receive abatacept in addition to standard GVHD prophylaxis (n=27). Children with serious NMHD (acquired or inherited bone marrow failure or hemoglobinopathy) undergoing mismatched (7/8) URD HSCT will be eligible, with blood samples obtained longitudinally to study the immunologic effects of abatacept. RESULTS: Pending. IMPACT: If successful, this trial will provide the foundation for a larger, more definitive multicenter, phase 3 trial of abatacept in the setting of URD HSCT for NMHD.