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)
Northwell Health
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.
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…
Eligibility
- Age range
- 14–100 years
- Sex
- All
- Healthy volunteers
- No
Inclusion Criteria: * Age ≥14 years * Karnofsky score ≥70% * No evidence of progressive bacterial, viral, or fungal infection * Creatinine clearance \>50 mL/min/1.72m2 * ALT and AST \<3 x the upper limit of normal * Total bilirubin \<2 x the upper limit of normal (except for Gilbert's syndrome) * Alkaline phosphatase ≤250 IU/L * Left Ventricular Ejection Fraction (LVEF) \>45% * Adjusted Carbon Monoxide Diffusing Capacity (DLCO) \>50% * Negative HIV serology * Negative pregnancy test: Confirmation per negative serum β-human chorionic gonadotropin (β-hCG) * Willing to comply with all study proc…
Interventions
- DrugCyclophosphamide
37.5 mg/kg IV over 1 hour on Day +3 and +4
- DrugAbatacept
Dose level 0: 10 mg/kg IV over 30-60 minutes on day +5 Dose level 1: 10mg/kg IV over 30-60 minutes on day +5 and +14 Dose level 2: 10mg/kg IV over 30-60 minutes on day +5, +14, and +28
- DrugBortezomib
1.3 mg/m2 IV 6 hours after graft infusion completion and 72 hours thereafter.
Location
- Northwell HealthNew Hyde Park, New York