The purpose of this study is to see: 1. If using these two drugs (carfilzomib and belatacept) together is safe 2. If the use of these two study drugs in addition to the usual immunosuppression for kidney transplant patients can improve your transplanted kidney function by lowering the antibodies you have against your transplanted kidney 3. If the study drugs effect the immune cells that were responding to your donor kidney. And, whether blood or urine tests can measure signs of inflammation and kidney cell injury 4. If using new computer techniques can help describe important changes seen on biopsy in your donated kidneys The primary objective is to assess the efficacy of carfilzomib and belatacept therapy when added to current treatment with steroids and maintenance immunosuppression, compared to conventional treatment alone, to improve the clinical outcome of renal transplant patients with active and chronic - active ABMR occurring more than 6 months after renal transplantation or less than 6 months post-transplant with persistent refractory Antibody-Mediated Rejection (ABMR)
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
100
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
RECRUITINGUCLA
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
RECRUITINGNYU Langone Health
New York, New York, United States
NOT_YET_RECRUITINGDuke University
Durham, North Carolina, United States
RECRUITINGUniversity of Cincinnati
Cincinnati, Ohio, United States
NOT_YET_RECRUITINGCleveland Clinic
Cleveland, Ohio, United States
RECRUITINGUniversity of Wisconsin - Madison
Madison, Wisconsin, United States
NOT_YET_RECRUITINGPart A: Incidence of reduction in Microvascular Inflammation (MVI) >=2 points
Time frame: 3-months post randomization and 12-months post receipt of Investigational Therapy (IT)
Part A: Incidence of reduction in the immunodominant donor-specific antibody (DSA) Mean Fluorescent Intensity (MFI) by >= 50%
Time frame: 3-months post randomization and 12-months post receipt of IT
Part B: The incidence of 20% improvement in estimated Glomerular Filtration Rate (eGFR) using the Chronic Kidney Disease - Epidemiology Collaboration (CKD-EPI 2021) slope
Time frame: 3-months post randomization and 12-months post receipt 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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