Efficacy Evaluation of Post-transplant Cyclophosphamide-based Graft-versus-host Disease Prophylaxis with ATG, Calcineurin Inhibitor-free, for Matched-sibling or Matched-unrelated Transplantation
Trial Snapshot
- Phase
- Phase 1
- Status
- Recruiting
- Sponsor
- Enrollment
- 50
- Locations
- 1
- Primary Endpoint
- Cumulative incidence of grades III-IV acute GVHD by the MAGIC criteria
Study Overview
Brief Summary
Hematopoietic stem cell transplantation is a curative treatment for a number of benign and malignant hematologic diseases. One of the key parts of hematopoietic stem cell transplantation is the prophylaxis of graft-versus-host disease. Since the end of the 1970s, with the introduction of cyclosporine, calcineurin inhibitors (cyclosporine and tacrolimus) have become part of almost all prophylactic regimens, even though they are a group of drugs with a poor toxicity profile that requires monitoring. constant serum level. Since 2008, post-transplant cyclophosphamide has been introduced with great success, associated with a calcineurin inhibitor and mycophenolate, in the prophylaxis of graft-versus-host disease in haploidentical transplantation (50% matched).
Since then, in view of this enormous success, efforts have been made to incorporate post-transplant cyclophosphamide in matched related and unrelated transplants, or with a mismatch.
This is a prospective, 2-arm, non-randomized study. Arm 1, with related donors, and arm 2, with unrelated donors. Patients will be allocated in these arms according to donor availability (patients with a matched-sibling donor will receive a matched-sibling transplant; patients with no related donors but with unrelated donors, an unrelated transplant).
Patients who are ready for transplantation with matched-sibling or unrelated donors will be recruited to participate in the study.
The stem cell collection target will be 5E6 CD34/kg recipient weight for peripheral source. If a quantity greater than this is collected, the remainder will be cryopreserved according to the institutional protocol.
Graft-versus-host disease prophylaxis will be performed on D+3 and D+4 with cyclophosphamide and with ATG on D-3 and D-2 for matched-sibling or unrelated donors transplants.
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Prevention
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 60 Years (Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Patient with (1) acute leukemia in first or second remission; (2) myelodysplasia with less than 20% blasts; (3) Hodgkin's or non-Hodgkin's lymphoma, in partial remission after salvage therapy
- •Who will receive a related or unrelated, HLA-compatible transplant;
- •Who is a transplant candidate with FluMel, FluTBI, CyTBI, BuCy or BuFlu conditioning;
- •Peripheral blood source;
- •Age between 18 and 60 years.
Exclusion Criteria
- •Hepatic dysfunction (transaminases x2 the normal value)
Arms & Interventions
Matched-sibling donor transplants
Matched sibling transplants will receive PTCy + ATG4.0
Intervention: Cyclophosphamide injection (Drug)
Matched-sibling donor transplants
Matched sibling transplants will receive PTCy + ATG4.0
Intervention: ATG 4.0 (Drug)
Matched unrelated donor transplants
Unrelated transplants will receive PTCy + ATG5.0
Intervention: ATG 5.0 (Drug)
Matched unrelated donor transplants
Unrelated transplants will receive PTCy + ATG5.0
Intervention: Cyclophosphamide injection (Drug)
Outcomes
Primary Outcomes
Cumulative incidence of grades III-IV acute GVHD by the MAGIC criteria
Time Frame: 6 months
Cumulative incidence of acute graft-versus-host disease, grades III-IV by the MAGIC criteria
Secondary Outcomes
- Cumulative incidence of grades II-IV acute GVHD by the MAGIC criteria(6 months)
- Cumulative incidence of chronic GVHD as defined by the NIH criteria(3 years)
- Cumulative incidence of steroid-requiring chronic GVHD as defined by the NIH criteria(3 years)
- Rate of overall survival(3 years)
- Cumulative incidence of steroid-refractory acute GVHD as defined by Mohty et al PMID 32756949(6 months)
- Cumulative incidence of non-relapse mortality, i.e., death not following disease relapse(3 years)
- Cumulative incidence of relapse, defined as > 5% blasts in bone marrow or 1% blasts in peripheral blood (acute leukemias/myelodysplasia) or biopsy proven relapse or positve PET-CT (lymphoma)(3 years)
- Rate of disease-free survival (death or relapse)(3 years)
- Cumulative incidence of clinically significant CMV reactivation (which led to antiviral treatment)(3 year)
- Cumulative incidence of posttransplant lymphoproliferative disorder (biopsy-proven or positive EBV PCR combined with clinical symptoms)(3 years)
- Cumulative incidence CMV disease (biopsy-proven CMV disease OR suggestive CMV+ BAL)(3 years)
- Measuremnt of quality of life using the FACT-BMT scale(2 years)