Targeting the B Cell Response to Treat Antibody-Mediated Rejection With Carfilzomib and Belatacept (CarBel)
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)
• Able to understand and agree to participate in the study.
• Have received a kidney transplant from a living or deceased donor (including re-transplants).
• Men and women must agree to use birth control during the study and for 3 months after the last dose of study drugs, or be surgically sterile or post-menopausal.
• Heart function must be good enough (LVEF of at least 40%) without severe heart issues or high blood pressure in the lungs.
• Must have been previously exposed to the Epstein-Barr Virus (EBV).
• Diagnosed with specific types of kidney transplant rejection based on criteria, with certain conditions on timing and treatment history.
• Kidney function must be at a certain level (eGFR of at least 30 ml/min/1.73 m²).
• Specific scores related to kidney biopsy results must be within certain limits.
• Must have a measurable level of specific antibodies against the donor kidney (HLA DSA) with a certain intensity.
⁃ Up-to-date vaccinations according to guidelines for transplant patients.
⁃ Must have a negative tuberculosis (TB) test and chest x-ray before enrollment, no symptoms or known contact with TB, and not have recently traveled to or lived in areas with high TB rates. If previously infected with TB, must have completed treatment and have a recent negative chest x-ray.
⁃ If previously infected with COVID-19, must be fully recovered for at least 21 days before joining the study. No COVID-19 test required for those without symptoms.