Immune Monitoring and CNI Withdrawal in Low Risk Recipients of Kidney Transplantation
Condition: Kidney Transplant Recipients
Intervention: Tacrolimus (CNI) Withdrawal; Standard Immunosuppressive Therapy
Intervention description: Recipients of living-donor kidney allografts are given induction therapy with rabbit antithymocyte globulin (RATG, Thymoglobulin®) and treated with a regimen of mycophenolate mofetil (MMF), prednisone and tacrolimus.
Subjects without any clinical acute rejection (AR) in the first 6 months, without borderline or acute rejection on the 6 month biopsy, and without donor-specific antibody (DSA) at anytime, including the 6 month test will be randomized (2:1) to tacrolimus (CNI) withdrawal.; Recipients of living-donor kidney allografts are given induction therapy with rabbit antithymocyte globulin (RATG, Thymoglobulin®) and treated with a regimen of mycophenolate mofetil (MMF), prednisone and tacrolimus.
Intervention MeSH terms: Mycophenolic Acid; Prednisone; Tacrolimus; Thymoglobulin; Antilymphocyte Serum; Immunosuppressive Agents; Calcineurin Inhibitors
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 52.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: recipients of living-donor kidney allografts; antithymocyte globulin (ATG) induction; calcineurin inhibitors (CNIs); CNI withdrawal

Summary:

      The study will compare how well transplanted kidneys work and the response of people's immune
      systems as tacrolimus, a calcineurin inhibitor (CNI), is withdrawn. In addition, this
      research study will evaluate whether reducing immunosuppression can decrease some of these
      side effects while still preventing rejection of the kidney.
    

Eligibility criteria:

        INCLUSION CRITERIA -

        Initial Enrollment/Screening: Patients who meet all of the following criteria are eligible
        for enrollment as study subjects:

          -  Subject must be able to understand and provide written informed consent;

          -  Primary living-donor (related or unrelated) kidney transplant recipients;

          -  Peak flow-based PRAs for class I and class II <30%(performed by local center);

          -  Current (within 8 weeks prior to transplantation) flow-based PRAs for class I and
             class II <30% (performed by local center);

          -  No donor specific antibody by flow solid phase method on the peak PRA serum (if serum
             available), or on the current PRA serum (within 8 weeks prior to transplantation)
             performed by central core laboratory. If the sera for the peak PRA is not available,
             then only the current PRA serum will be tested;

          -  Negative T-cell and B-cell crossmatch by flow cytometry (performed by local center);

          -  Female subjects of childbearing potential must have a negative pregnancy test (urine
             or serum) upon study entry;

          -  Female and male subjects with reproductive potential must agree to use FDA approved
             methods of birth control while participating in the study.

        Inclusion Criteria for Randomization:

        Participants who meet all of the following criteria are eligible for randomization:

          -  No history of acute rejection episodes;

          -  The pre-randomization protocol biopsy should confirm no rejection, including
             borderline rejection (based on the central pathology read);

          -  No donor specific antibody as detected by flow solid phase method (performed by the
             central core laboratory).

        EXCLUSION CRITERIA -

        Initial Enrollment/Screening:

        Participants who meet any of these criteria are not eligible for enrollment as study
        subjects:

          -  Recipient of multiple organ transplants;

          -  Prior history of organ transplantation;

          -  Deceased-donor source;

          -  Any condition that would preclude protocol biopsies;

          -  HLA identical recipients;

          -  Currently breast-feeding or plans to become pregnant during the timeframe of the study
             follow up period;

          -  Any condition that, in the opinion of the investigator, would interfere with the
             subject's ability to comply with study requirements;

          -  Inability or unwillingness to comply with study protocol;

          -  Use of investigational drugs within 4 weeks of study entry and for the duration of the
             study;

          -  Recent recipient of any licensed or investigational live attenuated vaccine(s) within
             two months of prior to study entry.

        Exclusion Criteria for Randomization:

        Participants who meet any of these criteria are not eligible for randomization:

          -  Subjects who receive less than 4.5mg/kg of Rabbit ATG (Thymoglobulin®) induction
             therapy;

          -  Subjects who test positive for BKV by PCR in the blood at 6 months post-transplant;

          -  Any condition that would preclude protocol biopsies;

          -  Currently breast-feeding or plans to become pregnant during the timeframe of the study
             follow up period;

          -  Any condition that, in the opinion of the investigator, would interfere with the
             subject's ability to comply with study requirements;

          -  Inability or unwillingness of a subject to give written informed consent or comply
             with study protocol;

          -  Use of investigational drugs within 4 weeks of study entry and for the duration of the
             study;

          -  Subjects who receive less than 1500 mg daily of Mycophenolate Mofetil (CellCept®) or
             equivalent.