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NCT Number: NCT06299462

PTCy and ATG for MSD and MUD Transplants

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.

Recruiting

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Key information

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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)

Treatment and study plan

ATG 5.0

Drug

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

Cyclophosphamide injection

Drug

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

ATG 4.0

Drug

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

Primary outcomes

  1. 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

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

    Time frame: 6 months

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

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

    Time frame: 6 months

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

  3. Cumulative incidence of chronic GVHD as defined by the NIH criteria

    Time frame: 3 years

    Cumulative incidence of chronic graft-versus-host disease

  4. Cumulative incidence of steroid-requiring chronic GVHD as defined by the NIH criteria

    Time frame: 3 years

    Cumulative incidence of steroid-requiring chronic graft versus host disease

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

    Time frame: 3 years

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

  6. 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)

    Time frame: 3 years

    Cumulative incidence of relapse of primary malignant disease

  7. Rate of overall survival

    Time frame: 3 years

    Death by any cause

  8. Rate of disease-free survival (death or relapse)

    Time frame: 3 years

    Composite outcome of death or primary disease relapse

  9. Cumulative incidence of clinically significant CMV reactivation (which led to antiviral treatment)

    Time frame: 3 year

    Incidence of cytomegalovirus reactivation

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

    Time frame: 3 years

    Incidence of posttransplant lymphoproliferative disorder

  11. Cumulative incidence CMV disease (biopsy-proven CMV disease OR suggestive CMV+ BAL)

    Time frame: 3 years

    Cumulative incidence of cytomegalovirus disease

  12. Measuremnt of quality of life using the FACT-BMT scale

    Time frame: 2 years

    Measurement quality of life

Study contacts

Contact information is provided by the study sponsor or research team.

Leonardo J Arcuri, MD, PhD

CONTACT

[email protected]

+5521981334715

Sponsors and collaborators

Lead sponsor

Instituto Nacional de Cancer, Brazil

Other Gov

Registry information

Official study 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

Important dates

Study start
2024
Primary completion
2031
Study completion
2031
First posted
Mar 7, 2024
Registry last updated
Feb 25, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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