NCT05289167

Post-Transplant Cyclophosphamide, Bortezomib and Abatacept for the Prevention of Graft-versus-Host-Disease (GvHD)

A Phase I-II Study of High-Dose Post-Transplant Cyclophosphamide, Bortezomib and Abatacept for the Prevention of Graft-versus-Host-Disease (GvHD) Following Allogenic Hematopoietic Stem Cell Transplantation (HSCT)

• Status: Active Not Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 74 (estimated)
• Sponsor: Northwell Health · Academic / Other
• Sex: All
• Age: 18 Years – 100 Years
• Healthy volunteers: Not accepted

Summary

This is a phase I-II clinical trial. Adult subjects with hematological malignancies undergoing allogeneic HSCT from an HLA matched sibling or ≥7 out of 8 allele level HLA matched unrelated donor are eligible for the study if they meet the criteria defined in our standard operation procedures (SOPs), meet all inclusion criteria, and do not satisfy any exclusion criteria. Subjects will receive a standard of care conditioning regimen. Subjects will receive investigational PTCy, investigational bortezomib and investigational abatacept as GvHD prophylaxis.

Detailed description

The study will have a phase I and phase II potions. The phase I portion will employ a 3+3 dose escalation design to define the maximum tolerated dose (MTD) of abatacept added to PTCy and bortezomib following HSCT. The phase II portion will consist of two single arm, open label, optimal 2-stage Simon design studies conducted in two separate strata for HLA matched and HLA mismatched donor transplants. Adult patients with hematological malignancies undergoing allogeneic HSCT from an HLA matched sibling or ≥7 out of 8 allele level HLA matched unrelated donor are eligible for the study if they meet the standard criteria defined in our institutional standard operation procedures (SOPs), meet all inclusion criteria, and do not satisfy any exclusion criteria. Subjects will receive a standard of care conditioning regimen followed by peripheral blood hematopoietic stem cells. Subjects with unrelated donors will also receive rabbit anti-thymocyte globulin (rATG). Subjects will receive investigational PTCy, investigational bortezomib and investigational abatacept as GvHD prophylaxis. The phase II portion dose of abatacept will be the MTD as determined in the phase I portion of the study. In the phase II portions, subjects will be stratified based on whether they receive a matched sibling or matched unrelated (matched) donor transplant and ≥7 out of 8, allele level matched (mismatched) unrelated donor transplant.

Conditions

• Graft-versus-host Disease

Interventions

Type	Name	Description
DRUG	Cyclophosphamide	50 mg/kg IV over 1 hour on Day +3 and +4
DRUG	Abatacept	Dose level 0: 10 mg/kg IV over 30 minutes on day +5 Dose level 1: 10mg/kg IV over 30 minutes on day +5 and +14 Dose level 2: 10mg/kg IV over 30 minutes on day +5, +14, and +28
DRUG	Bortezomib	1.3 mg/m2 IV 6 hours after graft infusion completion and 72 hours thereafter.

Timeline

• Start date: 2022-03-13
• Primary completion: 2025-12-01
• Completion: 2027-12-01
• First posted: 2022-03-21
• Last updated: 2024-12-27

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study