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: Not yet recruiting

Administrative data

• NCT number: NCT06299462
• Other study ID #: PTCy-ATG-001
• Status: Not yet recruiting
• Phase: Phase 1/Phase 2
• Start date: May 21, 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: Not yet 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
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Instituto Nacional de Cancer, 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