Phase 1 Study of Thiotepa-Based Conditioning with Reduced Post-Transplant Cyclophosphamide for Stem Cell Transplant in High-Risk Blood Cancers

What this Trial Is About

Researchers are evaluating a conditioning treatment involving Thiotepa, Busulfan, and Fludarabine combined with post-transplant cyclophosphamide PTCy in patients undergoing allogeneic stem cell transplantation alloSCT for high-risk blood cancers. This phase 1 trial aims to optimize PTCy dosing to reduce side effects and to strengthen anti-leukemia effects, hoping to improve outcomes like graft-versus-host disease and relapse-free survival in recipients of HLA-matched donor transplants. The study also explores biomarkers to personalize treatment intensity. Participants will receive one of two experimental conditioning regimens before receiving peripheral blood stem cell PBSC infusion. Both regimens include Thiotepa given five days before infusion, Fludarabine for four consecutive days prior, and Busulfan intravenously on two days before infusion. The two cohorts differ in Fludarabine dosage to represent low- and high-intensity conditioning. The PBSC infusion occurs on Day 0 following conditioning. During the study, participants will be closely monitored for outcomes including survival free of graft-versus-host disease and relapse at one year. Other assessments include time to neutrophil and platelet recovery, incidence of severe mucositis, pulmonary complications, infections, and graft failure up to one year post-transplant. Safety and treatment effects are evaluated through clinical and laboratory tests throughout the post-transplant period, with study completion expected by November 2030.

Thiotepa-based Conditioning Regimen With De-escalated Post-graft Cyclophosphamide for Allogeneic Stem Cell Transplantation in Hematologic Malignancies