Renal Allograft Tolerance Through Mixed Chimerism (Belatacept)

Inclusion criteria

• Male or female 18-60 years of age
• Candidate for a living-donor renal allograft from an HLA mismatched donor
• First or second transplant with either a living donor or cadaveric transplant as the first transplant.
• Use of FDA-approved methods of contraception by all recipients from the time that study treatment begins until 104 weeks (24 months) after renal transplantation.
• Ability to understand and provide informed consent.
• Serologic evidence of prior exposure to EBV.

Exclusion criteria

• ABO blood group-incompatible renal allograft.
• Evidence of anti-HLA antibody within 60 days prior to transplant as assessed by routine methodology (AHG and/or ELISA)
• Leukopenia or thrombocytopenia.
• Positive for HIV-1, hepatitis B core antigen, or hepatitis C virus; or positivity for hepatitis B surface antigen.
• Cardiac ejection fraction < 40% or clinical evidence of insufficiency.
• Forced expiratory volume FEV1 < 50% of predicted.
• Lactation or pregnancy.
• History of cancer other than basal cell carcinoma of the skin or carcinoma in situ of the cervix.
• Underlying renal disease etiology with a high risk of disease recurrence in the transplanted kidney (such as focal segmental glomerulosclerosis, type I or II membranoprolifertive glomerulonephritis).
• Prior dose-limiting radiation therapy.
• Known genetic disease or family history that may result in greater sensitivity to the effects of irradiation, or a physical deformity that would preclude adequate shielding or appropriate dosing during the irradiation component of the conditioning regimen.
• Enrollment in other investigational drug studies within 30 days prior to enrollment.
• Abnormal (>2 times lab normal) values for (a) liver function chemistries (ALT, AST, AP), (b) bilirubin, (c) coagulation studies (PT, PTT).
• Allergy or sensitivity to any component of belatacept, ATG, tacrolimus, or rituximab.
• Maintenance immunosuppression within 3 months prior to conditioning other than physiological doses of steroids, defined as ≤ 50 mg of hydrocortisone or dose equivalent.
• The presence of any medical condition that the investigator deems incompatible with participation in the trial.