MedPath

PTCy and ATG for MSD and MUD Transplants

Phase 1
Recruiting
Conditions
Acute Myeloid Leukemia
Acute Lymphoblastic Leukemia
Myelodysplastic Syndromes
Hodgkin Lymphoma
Non-hodgkin Lymphoma
Interventions
Registration Number
NCT06299462
Lead Sponsor
Instituto Nacional de Cancer, Brazil
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.

Detailed Description

Not available

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
50
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)

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Matched-sibling donor transplantsCyclophosphamide injectionMatched sibling transplants will receive PTCy + ATG4.0
Matched-sibling donor transplantsATG 4.0Matched sibling transplants will receive PTCy + ATG4.0
Matched unrelated donor transplantsATG 5.0Unrelated transplants will receive PTCy + ATG5.0
Matched unrelated donor transplantsCyclophosphamide injectionUnrelated transplants will receive PTCy + ATG5.0
Primary Outcome Measures
NameTimeMethod
Cumulative incidence of grades III-IV acute GVHD by the MAGIC criteria6 months

Cumulative incidence of acute graft-versus-host disease, grades III-IV by the MAGIC criteria

Secondary Outcome Measures
NameTimeMethod
Cumulative incidence of grades II-IV acute GVHD by the MAGIC criteria6 months

Cumulative incidence of acute graft-versus-host disease, grades II-IV by the MAGIC criteria

Cumulative incidence of chronic GVHD as defined by the NIH criteria3 years

Cumulative incidence of chronic graft-versus-host disease

Cumulative incidence of steroid-requiring chronic GVHD as defined by the NIH criteria3 years

Cumulative incidence of steroid-requiring chronic graft versus host disease

Rate of overall survival3 years

Death by any cause

Cumulative incidence of steroid-refractory acute GVHD as defined by Mohty et al PMID 327569496 months

Cumulative incidence of steroid-refractory graft-versus-host disease

Cumulative incidence of non-relapse mortality, i.e., death not following disease relapse3 years

Cumulative incidence of death not caused by primary malignant disease or following relapse

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

Cumulative incidence of relapse of primary malignant disease

Rate of disease-free survival (death or relapse)3 years

Composite outcome of death or primary disease relapse

Cumulative incidence of clinically significant CMV reactivation (which led to antiviral treatment)3 year

Incidence of cytomegalovirus reactivation

Cumulative incidence of posttransplant lymphoproliferative disorder (biopsy-proven or positive EBV PCR combined with clinical symptoms)3 years

Incidence of posttransplant lymphoproliferative disorder

Cumulative incidence CMV disease (biopsy-proven CMV disease OR suggestive CMV+ BAL)3 years

Cumulative incidence of cytomegalovirus disease

Measuremnt of quality of life using the FACT-BMT scale2 years

Measurement quality of life

Trial Locations

Locations (1)

Instituto Nacional de Cancer

🇧🇷

Rio de Janeiro, Brazil

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