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

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Kidney Transplantation

Intervention / Treatment
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* Drug: Mycophenolic Acid
* Drug: Standard of Care: CNI and MPA


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MPA monotherapy<br>Subjects will discontinue calcineurin inhibitor (cyclosporine or tacrolimus) and remain on MPA (mycophenolate mofetil or mycophenolate sodium) monotherapy | Drug: Mycophenolic Acid<br>* Mycophenolate mofetil: 750mg po bid x 36 months OR mycophenolate sodium 540mg po bid x 36 months<br>* Other names: cellcept, myfortic;|
| Active Comparator: Control: MPA and CNI<br>Subjects will continue with their current immunosuppressive regimen of MPA (mycophenolate mofetil or mycophenolate sodium) and calcineurin inhibitor (cyclosporine or tacrolimus) | Drug: Standard of Care: CNI and MPA<br>* Tacrolimus or cyclosporine: dosed according to trough levels per standard of care Mycophenolate mofetil 750mg po bid or mycophenolate sodium 540mg po bid x 36 months<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Kidney Allograft Rejection and Graft Loss |  | 36 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Renal Function Measured by Serum Creatinine and eGFR |  | 36 months | 
| Number of Incidences of Infection and Malignancy | Number of incidences of infection and malignancy will be reported. | 36 months | 
| Patient Survival | patient survival | 36 months | 
| Trans-vivo Delayed Type Hypersensitivity (DTH) Assay | 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. | 36 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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mycophenolate, living donor