This phase I/II trial tests the safety, side effects, and best dose of abatacept when given together with cyclophosphamide and bortezomib, and tests whether these drugs work after a donor stem cell transplant in preventing graft-versus-host disease (GvHD) in patients with blood cancers. GvHD is a common complication after an allogeneic transplant. Cyclophosphamide has been widely studied for the prevention of GvHD. Cyclophosphamide inhibits fast dividing cells, specifically T cells, that are involved in the development of GvHD. Abatacept has been shown to block the pathway of T cell activation and multiplication. T cells play a key role in the development of GvHD and why they are targeted with these medications to prevent GvHD. Bortezomib works by inhibiting dendritic cells, which also play a role in the development of GvHD. Giving cyclophosphamide, bortezomib and abatacept after a donor stem cell transplant may work better in preventing GvHD when compared to standard of care.
Additional locations may be listed on ClinicalTrials.gov for NCT05289167.
See trial information on ClinicalTrials.gov for a list of participating sites.
PRIMARY OBJECTIVES:
I. Determine the maximum tolerated dose (MTD) of post-transplant cyclophosphamide (PTCy), bortezomib, and abatacept following allogeneic hematopoietic stem cell transplantation (HSCT). (Phase I)
II. Estimate the incidence of grades II-IV acute GvHD in patients receiving PTCy, bortezomib and abatacept as GvHD prophylaxis in either strata defined by the type of donor. (Phase II)
SECONDARY OBJECTIVES:
I. Estimate the incidence of the following: Chronic GvHD in subjects receiving PTCy, bortezomib and abatacept, as GvHD prophylaxis, primary graft failure, poor graft function, and secondary graft failure, treatment-related mortality (TRM), relapse rate (RR), GvHD and relapse-free survival (GRFS), overall survival (OS).
II. Assess immune reconstitution by quantifying numbers of circulating CD3, CD4, CD8, and CD19 cells in comparison to established reference data.
OUTLINE: This is a phase I dose-escalation study of abatacept followed by a phase II study.
CONDITIONING: Patients receive 1 of 2 conditioning regimens as determined by the treating physician.
REGIMEN 1: Patients receive thiotepa intravenously (IV) once daily (QD) on days -6 and -5, fludarabine IV QD on days -4, -3, and -2, busulfan IV every 24 hours on days -4, -3, and -2, and lapine T-lymphocyte immune globulin (rATG) IV daily on days -4, -3 and -2.
REGIMEN 2: Patients receive fludarabine IV QD on days -7, -6, -5, -4, -3 and -2, busulfan IV QD on days -3 and -2, and rATG IV daily on days -4, -3 and -2.
TRANSPLANT: Patients undergo bone marrow or peripheral blood stem cell transplant on day 0.
GVHD PROPHYLAXIS: Patients receive bortezomib IV at 6 hours after transplant and on day 3 after transplant and cyclophosphamide IV over 1 hour on days 3 and 4. Patients also receive abatacept IV over 30 minutes on day 5, days 5 and 14, or days 5, 14, and 28.
Additionally, patients undergo blood sample collection throughout the study.
After completion of study treatment, patients are followed weekly until day 100, monthly up to day 180, and then every 3 months for up to 2 years.
Lead OrganizationLaura and Isaac Perlmutter Cancer Center at NYU Langone
Principal InvestigatorMohammad Maher Abdul-Hay
