The purpose of this study is to evaluate the safety and efficacy of carfilzomib and belatacept, administered with steroids and maintenance immunosuppression, in kidney transplant recipients with donor-specific antibody (DSA)-associated graft injury. Participants will be followed for 52 weeks after starting investigational therapy, including protocol biopsies at 3 months and 12 months after start of investigational therapy. The study will also assess changes in immune cell responses, blood and urine biomarkers, and biopsy-based pathomic features associated with antibody-mediated graft injury.
This is a prospective, multicenter, open-label study evaluating the safety and efficacy of carfilzomib and belatacept in kidney transplant recipients with donor-specific antibody-associated graft injury. Twenty-five participants will receive steroid pulse/taper, carfilzomib, belatacept, tacrolimus, mycophenolate, and prednisone according to protocol-defined dosing and maintenance immunosuppression. Participants will be followed for 12 months after initiation of investigational therapy, with protocol biopsies performed at 3 months and 12 months after start of investigational therapy. Participants who discontinue study treatment without withdrawing informed consent will continue follow-up to end of study.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
25
Administered by intravenous infusion over 60 minutes.
Administered by intravenous infusion over 30 minutes.
University of Alabama Medical Center
Birmingham, Alabama, United States
NOT_YET_RECRUITINGMayo Clinic Arizona
Phoenix, Arizona, United States
NOT_YET_RECRUITINGUCLA Medical Center (Site #: 71123)
Los Angeles, California, United States
NOT_YET_RECRUITINGNorthwestern University, Feinberg School of Medicine
Chicago, Illinois, United States
NOT_YET_RECRUITINGWashington University
St Louis, Missouri, United States
NOT_YET_RECRUITINGNYU Langone Health
New York, New York, United States
RECRUITINGDuke University
Durham, North Carolina, United States
NOT_YET_RECRUITINGUniversity of Cincinnati
Cincinnati, Ohio, United States
NOT_YET_RECRUITINGCleveland Clinic
Cleveland, Ohio, United States
NOT_YET_RECRUITINGUniversity of Wisconsin - Madison
Madison, Wisconsin, United States
NOT_YET_RECRUITINGProportion of subjects who do not meet a stopping rule for safety and remain free of all of the following: Grade 3 or higher infusion reaction, Grade 3 or higher infections, and any malignancy excluding localized non-melanomatous skin cancer.
Time frame: 3-months post randomization and 12-months post receipt of Investigational Therapy (IT)
Proportion of subjects achieving either (1) ≥50% reduction in MFI or clearance below positivity threshold of immunodominant DSA, or (2) >20% improvement in 12-month post-treatment eGFR slope vs pre-enrollment
Mean fluorescent intensity (MFI), donor-specific antibody (DSA), and estimated glomerular filtration rate (eGFR). The endpoint is the proportion of subjects achieving either: 1. 50% reduction in mean fluorescent intensity (MFI) or elimination below threshold for positivity of the immunodominant donor-specific antibody (DSA), or 2. improvement in 12-month post-treatment estimated glomerular filtration rate (eGFR) slope of greater than 20% compared with pre-enrollment eGFR slope
Time frame: 3-months post randomization and 12-months post receipt of IT
Change in albuminuria
Time frame: 3-months post randomization and 12-months post receipt of IT
Change in Banff lesion grading score (2022 criteria)
Time frame: 3-months post randomization and 12-months post receipt of IT
Change in immunodominant donor-specific antibody (DSA) MFI
Time frame: 3-months post randomization and 12-months post receipt of IT
Change in estimated Glomerular Filtration Rate (eGFR) (2022 criteria)
Time frame: 3-months post randomization and 12-months post receipt of IT
Incidence of Antibody-Mediated Rejection (ABMR)
Time frame: 3-months post randomization and 12-months post receipt of IT
Incidence of Acute Cellular Rejection (ACR)
Time frame: 3-months post randomization and 12-months post receipt of IT
Incidence of mixed ABMR/ACR
Time frame: 3-months post randomization and 12-months post receipt of IT
Change in iBox scores
Time frame: 3-months post randomization and 12-months post receipt of IT
Number of days hospitalized for administration of protocol
Time frame: From entry to week 52
Number of days hospitalized for any other reason
Time frame: From entry to week 52
Incidence of bacterial, viral, and fungal infections
Time frame: From entry to week 52
Incidence of de novo malignancy
Time frame: From entry to week 52
Time to all cause composite allograft loss
Allograft loss is defined as return to dialysis (continually for at least 30 days), allograft nephrectomy, re-transplantation, or death.
Time frame: 3-months post randomization and 12-months post receipt of IT
Time to all cause composite death-censored allograft loss
Death-censored allograft loss is defined as return to dialysis (continually for at least 30 days), allograft nephrectomy, or re-transplantation.
Time frame: 3-months post randomization and 12-months post receipt of IT
Time to patient death
Time frame: 3-months post randomization and 12-months post receipt of IT
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