A Phase I-II Study of High-Dose Post-Transplant Cyclophosphamide, Bortezomib, and Abatacept for the Prevention of Graft-Versus-Host Disease (GVHD) Following Allogeneic Hematopoietic Stem Cell Transplantation (HSCT)
The study will be conducted in two phases. The phase I portion will employ a 3+3 dose-escalation design to define the maximum tolerated dose (MTD) of abatacept added to PTCy and bortezomib following HSCT. The phase II portion will consist of two single-arm, open-label, optimal 2-stage Simon design studies conducted in two separate strata for HLA-matched and HLA-mismatched donor transplants.
• Age ≥18 years
• Karnofsky score ≥70%
• No evidence of progressive bacterial, viral, or fungal infection
• Creatinine clearance \>50 mL/min/1.72m2
• ALT and AST \<3 x the upper limit of normal
• Total bilirubin \<2 x the upper limit of normal (except for Gilbert's syndrome)
• ALP ≤250 IU/L
• LVEF \>45%
• Adjusted DLCO \>50%
• Negative HIV serology
• Negative pregnancy test: Confirmation per negative serum β-hCG
• Willing to comply with all study procedures and be available for the duration of the study.