PTCy and ATG for MSD and MUD Transplants

Acute Myeloid Leukemia Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06299462
• Other study ID #: PTCy-ATG-001
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: June 20, 2024
• Est. completion date: June 1, 2031

Study information

• Verified date: March 2024
• Source: Instituto Nacional de Cancer, Brazil
• Contact: Leonardo J Arcuri, MD, PhD
• Phone: +5521981334715
• Email: leonardojavier[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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-1 or on D-2 and D-1, depending on ATG de-escalation, for matched-sibling transplants, according to prespecified criteria based on the 3+3 approach; and on D+3 and D+4 with cyclophosphamide and with ATG on D-2 and D-1, for unrelated donors.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: June 1, 2031
• Est. primary completion date: June 1, 2031
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

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:

• Renal dysfunction (Cr > 1.5 mg/dL)

• Hepatic dysfunction (transaminases x2 the normal value)

Related Conditions & MeSH terms

• Acute Lymphoblastic Leukemia
• Acute Myeloid Leukemia
• Hodgkin Lymphoma
• Leukemia
• Lymphoma
• Myelodysplastic Syndromes
• Non-hodgkin Lymphoma
• Precursor Cell Lymphoblastic Leukemia-Lymphoma

Intervention

Drug:
• ATG 5.0
ATG 2.5 mg/kg on days -2 and -1
• Cyclophosphamide injection
Cyclophosphamide 50 mg/kg on days +3 and +4
• ATG 2.5±1.5
ATG 2.5 mg/kg on day -1 ± 1.5 mg/kg on day -2

Locations

Country	Name	City	State
Brazil	Instituto Nacional de Cancer	Rio de Janeiro

Sponsors (1)

Lead Sponsor	Collaborator
Instituto Nacional de Cancer, Brazil

Country where clinical trial is conducted

Brazil, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Cumulative incidence of grades II-IV acute GVHD by the MAGIC criteria	Cumulative incidence of acute graft-versus-host disease, grades II-IV by the MAGIC criteria	6 months
Secondary	Cumulative incidence of steroid-refractory acute GVHD as defined by Mohty et al PMID 32756949	Cumulative incidence of steroid-refractory graft-versus-host disease	6 months
Secondary	Cumulative incidence of chronic GVHD as defined by the NIH criteria	Cumulative incidence of chronic graft-versus-host disease	3 years
Secondary	Cumulative incidence of steroid-requiring chronic GVHD as defined by the NIH criteria	Cumulative incidence of steroid-requiring chronic graft versus host disease	3 years
Secondary	Cumulative incidence of non-relapse mortality, i.e., death not following disease relapse	Cumulative incidence of death not caused by primary malignant disease or following relapse	3 years
Secondary	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)	Cumulative incidence of relapse of primary malignant disease	3 years
Secondary	Rate of overall survival	Death by any cause	3 years
Secondary	Rate of disease-free survival (death or relapse)	Composite outcome of death or primary disease relapse	3 years
Secondary	Cumulative incidence of clinically significant CMV reactivation (which led to antiviral treatment)	Incidence of cytomegalovirus reactivation	3 year
Secondary	Cumulative incidence of posttransplant lymphoproliferative disorder (biopsy-proven or positive EBV PCR combined with clinical symptoms)	Incidence of posttransplant lymphoproliferative disorder	3 years
Secondary	Cumulative incidence CMV disease (biopsy-proven CMV disease OR suggestive CMV+ BAL)	Cumulative incidence of cytomegalovirus disease	3 years
Secondary	Measuremnt of quality of life using the FACT-BMT scale	Measurement quality of life	2 years