PTCy and ATG for MSD and MUD Transplants

NCT06299462 | Recruiting Phase 1

• 1 other identifier: PTCy-ATG-001
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

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.

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

Outcome Measures

Primary Outcomes (1)

• Cumulative incidence of grades III-IV acute GVHD by the MAGIC criteria

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

  6 months

Secondary Outcomes (12)

• Cumulative incidence of grades II-IV acute GVHD by the MAGIC criteria

  6 months

• Cumulative incidence of steroid-refractory acute GVHD as defined by Mohty et al PMID 32756949

  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

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

  3 years

Study Arms (2)

Matched-sibling donor transplants

EXPERIMENTAL

Matched sibling transplants will receive PTCy + ATG4.0

Drug: Cyclophosphamide injection; Drug: ATG 4.0

Matched unrelated donor transplants

EXPERIMENTAL

Unrelated transplants will receive PTCy + ATG5.0

Drug: ATG 5.0; Drug: Cyclophosphamide injection

Interventions

ATG 5.0 DRUG

ATG 2.5 mg/kg on days -3 and -2

Matched unrelated donor transplants

Cyclophosphamide injection DRUG

Cyclophosphamide 50 mg/kg on days +3 and +4

Matched unrelated donor transplants; Matched-sibling donor transplants

ATG 4.0 DRUG

ATG 2.5 mg/kg on day -2 + 1.5 mg/kg on day -3

Matched-sibling donor transplants

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• \- Hepatic dysfunction (transaminases x2 the normal value)

Sponsors & Collaborators

• Instituto Nacional de Cancer, Brazil: lead

Study Sites (1)

Instituto Nacional de Cancer

Rio de Janeiro, Rio de Janeiro, 20230-130, Brazil

RECRUITING

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Myelodysplastic Syndromes; Hodgkin Disease; Lymphoma, Non-Hodgkin; Graft vs Host Disease

Interventions

Cyclophosphamide

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, Lymphoid; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Bone Marrow Diseases; Lymphoma

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Study Officials

• Leonardo J Arcuri, MD, PhD

  Instituto Nacional de Cancer

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Leonardo J Arcuri, MD, PhD

CONTACT

+5521981334715; leonardojavier@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Model Details: 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

Study Record Dates

• First Submitted: March 13, 2023
• First Posted: March 7, 2024
• Study Start: June 14, 2024
• Primary Completion (Estimated): June 1, 2031
• Study Completion (Estimated): June 1, 2031
• Last Updated: February 25, 2025

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE

Locations

BR (1)