Renal Allograft Tolerance Through Mixed Chimerism (Belatacept)
Condition: Kidney Failure, Chronic; Renal Insufficiency
MeSH terms: Renal Insufficiency; Kidney Failure, Chronic
Intervention: Belatacept; ATG; Rituximab; Total Body Irradiation; Thymic Irradiation; Combined Bone Marrow/Kidney Transplantation
Intervention description: A selective T-cell (lymphocyte) costimulation blocker; A T-Cell Depleting Agent; B-Cell Depleting Agent
Intervention MeSH terms: Rituximab; Abatacept
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 2.0
Sex: All
Minimum age: 18 Years
Maximum age: 60 Years
Healthy volunteers: No
Keywords: ESRD

Summary:

      This study will examine the safety and effectiveness of a combination kidney and bone marrow
      transplant from a haplo-identical related donor. An investigational medication and other
      treatments will be given prior to and after the transplant to help protect the transplanted
      kidney from being attacked by the body's immune system
    

Eligibility criteria:

        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.