A Trial of Tolerogenic Immunosuppression in Highly Sensitized Renal Transplant Recipients

Study Overview
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Brief Summary
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Comparison between Campath induction and monotherapy with Tacrolimus vs Thymoglobulin induction and triple drug maintenance using Tacrolimus, mycophenolate, and steroids.

Detailed Description
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Recent reports suggest that it might be possible to induce a state of tolerance in solid organ transplantation. So called tolerogenic immunosuppression involves induction with lymphocyte depleting antibodies followed by monotherapy with calcineurin inhibitors, cyclosporin or tacrolimus. The proposed study aims to evaluate a protocol of immunosuppression induction with lymphocyte depleting antibody Campath given prior to graft reperfusion, followed by tacrolimus monotherapy in highly sensitized patients (PRA >14% or past historical =/>50% and/or multiple renal transplants) undergoing renal transplantation, and compare it with the current standard protocol at UTMB which employs induction with Thymoglobulin given over 4 days followed by 3 drugs: tacrolimus, mycophenolate and steroids. In both groups of patients the target tacrolimus levels will be the same i.e, between 10 to 15ng/mL, soon after the transplant. In the Campath gro up, tacrolimus will be tapered after 3 months in patients who do not have rejection and appear to be developing donor specific tolerance.

Official Title
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Comparison of Two Different Immunosuppression Protocols in Highly Sensitized Renal Transplant Recipients: Campath Induction With Tacrolimus Monotherapy vs Thymoglobulin Induction With Triple Drug Protocol.

Conditions
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Kidney Diseases

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males and females aged 18-75 years. Recipients of multiple kidney transplants Patients with a PRA >14% and/or a past historical PRA greater or equal to 50%. Females of childbearing potential must have a negative pregnancy test prior to inclusion. Patients who are willing and able to participate in the full course of the study and from whom written informed consent has been obtained. Exclusion Criteria: Patients with a history of malignancy within the last 5 years, except excised squamous or basal cell carcinoma of the skin. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after contraception and until the termination of gestation,confirmed by a positive human chorionic gonadotropin(hCG) laboratory test. Patients who are HIV positive. Patients with symptoms of significant somatic or mental illness or evidence of current drug and/or alcohol abuse.

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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Group 1 Standard Immunosuppression<br>Anti-thymocyte Globulin (Rabbit)] ,tacrolimus, mycophenolate mofetil and prednisone Patients with End Stage Renal Disease (ESRD) and high Panel Reactive Antibody (PRA) who randomize to the control group. These patients will get induction therapy prior to transplant with Thymoglobulin 1.5 mg/kg/day for 4 days to a total dose of 6mg/kg. They will receive maintenance immunosuppression with three drugs : tacrolimus, cellcept and prednisone. | |
| Group 2 Campath Immunosuppression<br>Alemtuzumab,tacrolimus Patients with ESRD and high PRA who randomize to the study group. These patients will get induction therapy prior to reperfusion of the kidney, during the transplant operation, with Campath (Alemtuzumab) 30mg, one dose. They will receive maintenance immunosuppression with tacrolimus alone (monotherapy). | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| graft survival | Cumulative graft survival at 1 year | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| rejection episodes | 1 year cumulative freedom from rejection | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Kidney transplant, Tolerance induction, High Panel Reactive Antibody (PRA) kidney recipients