PTCy, sirolimus, MMF and RGI-2001 to explore regulatory T-cell expansion following haploidentical peripheral blood stem cell transplantation: a pilot study.

In this single-arm pilot study, a novel regimen of post-transplant cyclophosphamide (PTCy), sirolimus, mycophenolate mofetil (MMF) and RGI-2001 was investigated to explore regulatory T-cell (T-reg) expansion in the setting of haploidentical allogeneic hematopoietic cell transplantation (HCT). RGI-2001 was infused at 100 ug/kg per dose, for six weekly doses. The primary endpoint was feasibility, assessed by the proportion of participants who were able to receive ≥4 doses of RGI-2001. Twenty-five participants enrolled. The primary endpoint was achieved by 80% of participants, deeming the regimen feasible. Longitudinal immune monitoring demonstrated recovery of T-reg subsets following HCT. The estimated probabilities of grades III-IV acute GVHD by day +180 was 12%, and moderate-severe chronic GVHD by 1 year was 28%. The regimen of PTCy, sirolimus, MMF and RGI-2001 was feasible. Future studies should evaluate optimized sequencing and dosing strategies to maximize the immunomodulatory effects of RGI-2001. This trial was registered at www.clinicaltrials.gov as NCT04473911.