Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) With Low-Dose Post-Transplant Cyclophosphamide for Prophylaxis of Graft-versus-Host Disease in Hematological Malignancies
Summary
This Phase 2, single-arm, open-label study aims to evaluate the safety and efficacy of low-dose (25 mg/kg) post-transplant cyclophosphamide (PTCy) for prophylaxis of Graft-versus-Host Disease (GVHD) in patients undergoing allogeneic stem cell transplantation following reduced-intensity or non-myeloablative conditioning. The study will focus on matched sibling, matched unrelated, and haploidentical peripheral blood stem cell donors. The primary endpoint is 1-year GVHD-Free Relapse-Free Survival (GRFS). The study seeks to determine if low-dose PTCy offers similar outcomes as higher doses, with potentially reduced toxicity.
Detailed description
This study investigates the use of low-dose post-transplant cyclophosphamide (PTCy) for GVHD prophylaxis in a Phase 2, single-arm design. It involves patients receiving allogeneic stem cell transplantation with peripheral blood stem cells from matched sibling, matched unrelated, and haploidentical donors, following reduced-intensity or non-myeloablative conditioning. The aim is to evaluate 1-year GVHD-Free Relapse-Free Survival (GRFS) using 25 mg/kg of PTCy administered on days +3 and +4, in combination with tacrolimus and mycophenolate mofetil (MMF). The study builds on previous research that has shown the effectiveness of PTCy in preventing GVHD in various transplant settings, including haploidentical and matched unrelated donors. Lower doses of PTCy, such as 25 mg/kg, have been shown to be effective in other settings with reduced toxicity compared to the standard 50 mg/kg dose, and this study will assess whether the same holds true for peripheral blood stem cell transplants. The findings from this trial will help determine the optimal dosing strategy for PTCy in GVHD prophylaxis, with the potential to improve patient outcomes by minimizing toxicity while maintaining efficacy.
Arms & interventions
- DrugCyclophosphamide (primary intervention for GVHD prophylaxis)
This study evaluates the use of low-dose (25 mg/kg) post-transplant cyclophosphamide (PTCy) for prophylaxis of Graft-versus-Host Disease (GVHD) following allogeneic stem cell transplantation. The intervention involves administering PTCy on days +3 and +4 post-transplant, in combination with tacrolimus and mycophenolate mofetil (MMF) for GVHD prevention. The goal is to assess the safety and efficacy of this regimen in patients undergoing reduced-intensity or non-myeloablative conditioning using peripheral blood stem cells from matched sibling, matched unrelated, and haploidentical donors
Outcome measures
Primary
Number of Subjects Without Grade III/IV Acute Graft-Versus-Host Disease (GVHD) at 1 Year
The number of subjects without Grade III/IV acute graft-versus-host disease (GVHD) at one year following allogeneic stem cell transplantation, assessed using the Modified Glucksberg Criteria (Grade III: severe organ involvement, e.g., skin stage 3-4, liver or gut stage 2-3; Grade IV: life-threatening dysfunction, e.g., skin, liver, or gut stage 4).
Time frame: 1 year post-transplant
Number of Subjects Without Chronic Graft-Versus-Host Disease (GVHD) Requiring Systemic Treatment at 1 Year
The number of subjects without chronic graft-versus-host disease (GVHD) requiring systemic treatment (e.g., corticosteroids or immunosuppressive therapy) at one year following allogeneic stem cell transplantation with low-dose post-transplant cyclophosphamide (25 mg/kg), assessed per the NIH Consensus Criteria for chronic GVHD.
Time frame: 1 year post-transplant
Number of Subjects Without Relapse or Disease Progression at 1 Year
The number of subjects without relapse or disease progression at one year following allogeneic stem cell transplantation, defined as the reappearance of the underlying disease or worsening of disease burden, assessed by standard clinical and laboratory measures (e.g., bone marrow biopsy, or disease-specific markers such as minimal residual disease \[MRD\] testing) per the study protocol.
Time frame: 1 year post-transplant
Eligibility criteria
Study locations (1)
Penn State Cancer Institute
Hershey, Pennsylvania, 17033