Phase 1 Study of Immunosuppression-Free Regulatory T-Cell Engineered Haploidentical Stem Cell Transplantation for Relapsed, Refractory, and Ultra-High-Risk AML and MDS

What this Trial Is About

Researchers are evaluating the safety and effectiveness of an immunosuppression-free regulatory T-cell graft-engineered haploidentical hematopoietic stem cell transplant HSCT method in people with relapsed or refractory and ultra-high risk acute myeloid leukemia AML and myelodysplastic syndromes MDS. The study aims to reduce the risk of disease relapse and prevent common transplant complications such as graft-versus-host disease GVHD, which occurs when donor immune cells attack the recipients tissues. This is a Phase 1 pilot study supported by Dana-Farber Cancer Institute and Regeneron Pharmaceuticals, involving about 30 participants. Participants receive a conditioning regimen that includes radiation either Total Myeloid and Lymphoid Irradiation or Total Body Irradiation combined with chemotherapy drugs such as Fludarabine, Thiotepa, Cyclophosphamide, Mesna, and Melphalan depending on the cohort and intensity of treatment. On specific days before transplant, participants are given infusions of Treg-enriched donor cells the experimental therapy, unmodified donor T cells including cancer-fighting T effector cells, and a transplant of CD34 haploidentical peripheral blood stem cells. The treatment schedules vary slightly among three cohorts based on disease status and risk classification. During the study, participants are closely monitored with assessments at several time points up to one year post-transplant. These include evaluations for minimal residual disease MRD, GVHD, and overall health status. The study tracks dose-limiting toxicities, engraftment rates, graft failure, survival rates, and relapse occurrences. Participants undergo various tests and follow-up visits to assess treatment effects and safety, with the total participation lasting about one year after transplantation.

IS-free Treg HaploHCT