NCT06681922

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

• Status: Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 10 (estimated)
• Sponsor: Northwell Health · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The study will be conducted in two phases. 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.

Detailed description

The study will be conducted in two phases. 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 portion, 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 Vs Host Disease

Interventions

Type	Name	Description
DRUG	Cyclophosphamide, Bortezomib, Abatacept	Drug given for prevention of Graft-versus-Host Disease (GvHD) following Allogeneic Hematopoietic Stem Cell Transplantation (HSCT)

Timeline

• Start date: 2024-09-23
• Primary completion: 2027-10-01
• Completion: 2027-10-01
• First posted: 2024-11-12
• Last updated: 2024-12-16

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study