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: Drug: Cyclophosphamide injection; Drug: ATG 5.0; Drug: ATG 4.0

• 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

Study Timeline

• Study First Submitted: 2023-03-13
• Status Verified: 2024-03
• Study First Submitted QC: 2024-03-05
• Study First Posted: 2024-03-07
• Study Start: 2024-06-14
• Last Update Submitted: 2025-02-21
• Last Update Posted: 2025-02-25
• Primary Completion: 2031-06-01
• Study Completion: 2031-06-01

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

Group	Intervention	Description
Matched-sibling donor transplants	Cyclophosphamide injection	Matched sibling transplants will receive PTCy + ATG4.0
Matched-sibling donor transplants	ATG 4.0	Matched sibling transplants will receive PTCy + ATG4.0
Matched unrelated donor transplants	ATG 5.0	Unrelated transplants will receive PTCy + ATG5.0
Matched unrelated donor transplants	Cyclophosphamide injection	Unrelated transplants will receive PTCy + ATG5.0

Primary Outcome Measures

Name	Time	Method
Cumulative incidence of grades III-IV acute GVHD by the MAGIC criteria	6 months	Cumulative incidence of acute graft-versus-host disease, grades III-IV by the MAGIC criteria

Secondary Outcome Measures

Name	Time	Method
Cumulative incidence of grades II-IV acute GVHD by the MAGIC criteria	6 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 criteria	3 years	Cumulative incidence of chronic graft-versus-host disease
Cumulative incidence of steroid-requiring chronic GVHD as defined by the NIH criteria	3 years	Cumulative incidence of steroid-requiring chronic graft versus host disease
Rate of overall survival	3 years	Death by any cause
Cumulative incidence of steroid-refractory acute GVHD as defined by Mohty et al PMID 32756949	6 months	Cumulative incidence of steroid-refractory graft-versus-host disease
Cumulative incidence of non-relapse mortality, i.e., death not following disease relapse	3 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 scale	2 years	Measurement quality of life

Trial Locations

Locations (1)

Instituto Nacional de Cancer; 🇧🇷 Rio de Janeiro, Brazil