Mycophenolic Acid Monotherapy in Recipients of HLA-identical Living-Related Transplantation

Phase 2

Terminated

Brief Summary: This randomized trial will enroll adult recipients of HLA-identical living kidney transplants who are at least 1 year post-transplant. All subjects will be taking Prograf (tacrolimus) or cyclosporine and mycophenolic acid (CellCept or Myfortic) and then be randomized (1:2) to either continue calcineurin inhibitors or to taper off of calcineurin inhibitors. The hypothesis is that mycophenolic acid monotherapy permits long-term rejection-free renal allograft function in the absence of long-term calcineurin inhibitors in this fully matched renal transplant cohort.

Detailed Description: The objective of the study is to safely move HLA-identical renal transplant recipients from 2 immunosuppressive drugs (calcineurin inhibitor and mycophenolic acid) to mycophenolic acid monotherapy. Safety will be assessed by monitoring renal function in subjects in the withdrawal group compared to those who remain on the standard 2-drug immunosuppression protocol. Results of immunological monitors such as DTH regulation in response to donor minor antigens and development of anti-donor antibodies will be correlated with successful withdrawal.

Recruitment & Eligibility

Inclusion Criteria

Male or female subjects 18-75 years of age.
Subjects who are recipients of HLA-identical living donor renal allografts from a sibling and are at least 1 year post transplant, their donors and mothers.
Subjects must be capable of understanding the purpose and risks of the study and must sign a statement of informed consent.

Exclusion Criteria

GFR <40ml/min;
diagnosis of SLE,
Subjects with proteinuria (defined as a protein:creatinine ratio of >1 or an amount less than this deemed significant on an individual subject basis by the principal investigator),,
multi-organ transplant;
known hypersensitivity to, Prograf, Neoral, CellCept or Myfortic;
history of documented post transplant non-compliance with medications, transplant clinic or laboratory follow-up;
therapy with an investigational immunosuppressive drug within 6 weeks of study entry;
history of a psychological illness or condition such as to interfere with the patient's ability to understand the requirements of the study;
patients on less than 500 mg PO BID of CellCept or 360 mg PO BID of Myfortic at the time of potential randomization,
history of humoral rejection post transplant,
maintenance or for cause treatment with steroids (prednisone) within 3 months of enrollment.

Arm && Interventions

Group	Intervention	Description
MPA monotherapy	Mycophenolic Acid	Subjects will discontinue calcineurin inhibitor (cyclosporine or tacrolimus) and remain on MPA (mycophenolate mofetil or mycophenolate sodium) monotherapy

Primary Outcome Measures

Name	Time	Method
Incidence of Kidney Allograft Rejection and Graft Loss	36 months

Secondary Outcome Measures

Name	Time	Method
Number of Incidences of Infection and Malignancy	36 months	Number of incidences of infection and malignancy will be reported.
Trans-vivo Delayed Type Hypersensitivity (DTH) Assay	36 months	Delayed type hypersensitivity (DTH) reactivity status to donor and minor antigens will be detected using trans-vivo DTH assay. This information will help determine if T-regulatory cells are present, and whether such cells predict outcome of Calcineurin inhibitor withdrawal.
Renal Function Measured by Serum Creatinine and eGFR	36 months
Patient Survival	36 months	patient survival