Carfilzomib and Belatacept for Desensitization

Eligibility Criteria

• 1. Subject must be able to understand and provide informed consent
• 2. End stage renal disease (ESRD) on dialysis
• 3. United Network for Organ Sharing (UNOS) listed for a kidney transplant with any one of the following:
• * Current calculated panel reactive antibodies (cPRA) ≥ 99.9 percent awaiting deceased donor transplant
• * Current cPRA \>98 percent (with \>5 years of waiting time) awaiting deceased donor transplant
• * Current cPRA \>98 percent with Human Leukocyte Antigen (HLA)-incompatible approved living donor and has not received a transplant after 1 year in a kidney paired exchange program
• 4. Evidence of established immunity to Epstein-Barr virus (EBV) as demonstrated by serologic testing
• 5. Negative result of most recent tuberculosis (TB) testing or appropriately completed latent tuberculosis infection (LTBI) therapy.
• * Testing should be conducted using either a purified protein derivative (PPD) or interferon-gamma release assay (i.e. QuantiFERON-TB, T-SPOT.TB).
• * Negative results from tests performed within 12 months prior to study entry are acceptable in the absence of any intervening exposure to TB.
• * Subjects with a positive test result must have completed appropriate therapy for LTBI.
• * Note: LTBI treatment regimens should be among those endorsed by the Centers for Disease Control and Prevention (CDC), url: https://www.cdc.gov/tb/topic/treatment/ltbi.htm
• 6. Negative Food and Drug Administration (FDA)-approved test for human immunodeficiency virus (HIV) diagnosis (at screening or as documented in medical record, up to 6 months prior to screening)
• 7. Negative Hepatitis C antibody test at screening or as documented in medical record, up to 6 months prior to screening.
• 8. Negative result for SARS-CoV-2 by an FDA-authorized molecular diagnostic test. Examples include, but are not limited to RT-PCR, LAMP, TMA, and qSTAR.
• 9. Subjects must have an echocardiogram within the previous 1 year without any of the following findings:
• * severe left ventricular hypertrophy (LVH)
• * greater than mild LVH accompanied by diastolic dysfunction
• * left ventricular ejection fraction \<40 percent
• * pulmonary hypertension defined as right ventricular systolic pressure \>35 mm Hg or tricuspid regurgitant velocity \>2.8 m/s
• 10. Female subjects of reproductive potential must have a negative pregnancy test upon study entry
• 11. All subjects of reproductive potential must agree to use contraception for the duration of the study
• 12. Subjects must have current vaccinations or documented immunity to:
• * varicella (chickenpox)
• * measles
• * hepatitis B
• * pneumococcus
• * influenza, and
• * varicella zoster (if ≥ 50 years old).
• * Note: If subjects require administration of either live or killed vaccines to meet eligibility requirements, they must wait at least 2 weeks between vaccination and the baseline visit (i.e., at least 4 weeks before initiation of therapy)
• 1. Inability or unwillingness of a subject to give written informed consent or comply with study protocol
• 2. Known active current or history of invasive fungal infection, non-tuberculous mycobacterial infection
• 3. Hepatitis B surface antigen or core antibody positive
• 4. Serious uncontrolled concomitant major organ disease, excluding kidney failure
• 5. Chronic respiratory failure
• 6. Uncontrolled systemic hypertension
• 7. Previous non-kidney solid organ transplant or bone marrow transplant
• 8. Any infection requiring hospitalization and intravenous (IV) therapy within 4 weeks of screening or oral therapy within 2 weeks of screening
• 9. Primary or secondary immunodeficiency
• 10. History of thromboembolism (except thrombosis of dialysis vascular access site)
• 11. Subjects with myocardial infarction within 12 months of screening or cardiac dysrhythmias uncontrolled by medications
• 12. History of plasma cell dyscrasia
• 13. Known bleeding diathesis or coagulation abnormality
• 14. History of active tuberculosis (TB) (even if treated)
• 15. Malignancy within the last 5 years except treated basal and squamous cell cancer of the skin or treated cervical cancer in situ
• 16. Women who are currently pregnant or nursing
• 17. Alcohol, drug, or chemical abuse within 1 year
• 18. Treatment with any investigational agent within 4 weeks (or 5 half-lives of investigational drug, whichever is longer) of screening
• 19. Current treatment with other biological drug. If the potential subject receives standard of care antibody treatments for prophylaxis of COVID-19 (permitted in protocol), there must be a minimum interval of 2 weeks after this treatment and before initiation of the study therapy.
• 20. Current treatment with any medication which increases the risk of thromboembolic events including oral contraceptives
• 21. Currently smoking tobacco
• 22. Neutropenia (absolute neutrophil count \<1000/microliter) or thrombocytopenia (platelet count \<100,000/microliter) within 4 weeks prior to screening
• 23. Alanine Aminotransferase (ALT) or aspartate aminotransferase (AST) ≥3 times upper limit of normal (ULN) or total bilirubin ≥ 2 times ULN
• 24. Past or current medical problems or findings from physical examination or laboratory testing not listed above, which, in the opinion of the investigator, may:
• * pose additional risks from participation in the study
• * interfere with the subject's ability to comply with study requirements, or
• * impact the quality or interpretation of the data obtained from the study.
• 1. There are no exclusion criteria for living donors.