Clinical trial NCT06299462: PTCy and ATG for MSD and MUD Transplants
Official title: Efficacy Evaluation of Post-transplant Cyclophosphamide-based Graft-versus-host Disease Prophylaxis with ATG, Calcineurin Inhibitor-free, for Matched-sibling or Matched-unrelated Transplantation
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Acute Myeloid Leukemia
Acute Lymphoblastic Leukemia
Myelodysplastic Syndromes
Hodgkin Lymphoma
Non-hodgkin Lymphoma
Keywords: posttransplant cyclophosphamide
ATG
calcineurin-free GVHD prophylaxis
graft-versus-host disease
Lead sponsor: Instituto Nacional de Cancer, Brazil
Sponsor class: OTHER_GOV
First posted: 2024-03-07
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Patients with a matched sibling donor will be assigned to the PTCy+ATG4.l0 arm, while patients with a matched unrelated donor will be assigned to the PTCy+ATG5.0 arm
Primary purpose: PREVENTION

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.


Eligibility criteria: 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)

Primary outcomes:
measure: Cumulative incidence of grades III-IV acute GVHD by the MAGIC criteria
timeFrame: 6 months
Secondary outcomes:
measure: Cumulative incidence of grades II-IV acute GVHD by the MAGIC criteria
timeFrame: 6 months
measure: Cumulative incidence of steroid-refractory acute GVHD as defined by Mohty et al PMID 32756949
timeFrame: 6 months
measure: Cumulative incidence of chronic GVHD as defined by the NIH criteria
timeFrame: 3 years
measure: Cumulative incidence of steroid-requiring chronic GVHD as defined by the NIH criteria
timeFrame: 3 years
measure: Cumulative incidence of non-relapse mortality, i.e., death not following disease relapse
timeFrame: 3 years
measure: 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)
timeFrame: 3 years
measure: Rate of overall survival
timeFrame: 3 years
measure: Rate of disease-free survival (death or relapse)
timeFrame: 3 years
measure: Cumulative incidence of clinically significant CMV reactivation (which led to antiviral treatment)
timeFrame: 3 year
measure: Cumulative incidence of posttransplant lymphoproliferative disorder (biopsy-proven or positive EBV PCR combined with clinical symptoms)
timeFrame: 3 years
measure: Cumulative incidence CMV disease (biopsy-proven CMV disease OR suggestive CMV+ BAL)
timeFrame: 3 years
measure: Measuremnt of quality of life using the FACT-BMT scale
timeFrame: 2 years
Other outcomes:
Locations:
city: Rio de Janeiro
country: Brazil
facility: Instituto Nacional de Cancer
Study officials:
affiliation: Instituto Nacional de Cancer
name: Leonardo J Arcuri, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: