Effectiveness and Safety of Campath in Combination With Tacrolimus Monotherapy to Prevent Kidney Graft Rejection

Study Overview
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Brief Summary
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The purpose of this study is to determine whether Campath following Tacrolimus monotherapy is more effective in the prevention of renal graft rejection (considering an acute rejection rate of 5% for Campath-1H/Tacrolimus and of 22% for Tacrolimus/MMF/Steroids).

Detailed Description
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Major advances in immunosuppressive therapy have resulted in long-term graft survival by the use of various drug combinations.However, these combinations carry the risk of e.g. infection, malignancy, renal damage, hypertension, diabetes, hyperlipidemia, hirsutism, cushingoid facial appearance and bone necrosis.Therefore one of the major goals should be to reduce immunosuppression without increasing risk of rejections. Based on good results of a pilot study (not a single acute rejection episode during the 18-20 months observation period despite low level of Tacrolimus and absence of steroids) this randomised trial was designed to further evaluate the safety and efficacy of Campath-1H.

Official Title
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Effectiveness and Safety of Campath-1H as an Induction Agent in Combination With Tacrolimus Monotherapy for Prevention of Graft Rejection Compared to Tacrolimus in Combination With MMF and Steroids in Cadaveric Kidney Transplantation

Conditions
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Kidney Transplantation

Intervention / Treatment
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* Drug: Alemtuzumab
* Drug: Tacrolimus
* Drug: Alemtuzumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: age 18-65 endstage renal failure with no previous renal transplantation cadaveric donor written informed consent Exclusion Criteria: pregnant or nursing women multi-organ transplant recipients live donor recipients re-transplants panel reactive antibodies (PRA) > 25% previous treatment with Campath-1H use of other investigational agents within 6 weeks active systemic infection HIV positive patient or donor positive lymphocyte cytotoxicity cross-match between recipient serum and donor cells past history of anaphylaxis following exposure to humanized monoclonal antibodies

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Campath-1H 20 mg<br>Day 0: Immediately post transplant surgery patients will receive methylprednisolone 250 mg IV followed one hour later by Campath-1H 20 mg IV infusion over 3-6 hours. Day 1: Same protocol of Campath-1H and methylprednisolone as on Day 0. Day 2: No treatment Day 3: Initial dose of Tacrolimus 0,1 mg/kg/d (0,05 mg/kg/bid) till Month 6: Aim at blood level of 8-12 ng/ml (try to prevent the Tacrolimus trough level falling below 10 ng/ml in the first 3 months). Month 7-12: Maintain the Tacrolimus blood level at 5-8 ng/ml after 6 months. | Drug: Alemtuzumab<br>* Day 0: Campath-1H 20 mg IV infusion over 3-6 hours Day 1: Campath-1H 20 mg IV infusion over 3-6 hours<br>* Other names: MABCAMPATH;|
| Active Comparator: Tacrolimus<br>Day 0: Immediately post transplant surgery patients will receive methylprednisolone 250 mg IV followed one hour later by Campath-1H 30 mg IV infusion over 3-6 hours. Day 1: No treatment Day 2: Initial dose Tacrolimus 0.1 mg/kg/d (0.05 mg/kg.bid). till Month 6: Aim at blood level of 8-12 ng/ml (try to prevent the Tacrolimus trough level falling below 10 ng/ml in the first 3 months). Month 7-12: Maintain the Tacrolimus blood level at 5-8 ng/ml after 6 months. | Drug: Tacrolimus<br>* Day 0: Tacrolimus will be given pre-operatively or immediately post transplant surgery. The recommended initial daily starting dose is 0,1 mg/kg/d orally (0,05 mg/kg/bid) to aim at a whole blood level of 8-12 ng/ml. till Month 6: Aim at blood level of 8-12 ng/ml (try to prevent the Tacrolimus trough level falling below 10 ng/ml in the first 3 months). Month 7-12: Maintain the Tacrolimus blood level at 5-8 ng/ml after 6 months.<br>* Other names: Advagraf;|
| Experimental: Campath-1H 30 mg<br>Day 0: Immediately post transplant surgery patients will receive methylprednisolone 250 mg IV followed one hour later by Campath-1H 30 mg IV infusion over 3-6 hours. Day 1: No treatment. Day 2: Initial dose Tacrolimus 0.1 mg/kg/d (0.05 mg/kg.bid). till Month 6: Aim at blood level of 8-12 ng/ml (try to prevent the Tacrolimus trough level falling below 10 ng/ml in the first 3 months). Month 7-12: Maintain the Tacrolimus blood level at 5-8 ng/ml after 6 months. | Drug: Alemtuzumab<br>* Day 0: Campath-1H 30 mg IV infusion over 3-6 hours Day 1: Campath-1H 30 mg IV infusion over 3-6 hours<br>* Other names: MABCAMPATH;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Biopsy proven acute rejection episodes 6 months after transplantation (Banff Classification) |  | Month 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Biopsy proven acute rejection episodes 12 months after transplantation (Banff Classification) |  | Year 1 | 
| Time to 1st biopsy proven acute rejection episode (Banff Cl.) |  | Year 1 | 
| Patient and graft survival |  | Year 1 | 
| Number of patients who will get antilymphocyte preparation for treatment of steroid resistant acute rejection episodes |  | Year 1 | 
| Treatment failure defined as change from immunosuppressive protocol because of biopsy proven intractable rejection |  | Year 1 | 
| Adverse events (e.g. infections, PTLD) |  | Year 1 | 
| Creatinine clearance |  | Year 1 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Campath-1H, Alemtuzumab, Tacrolimus, renal transplantation, immunosuppression, prevention of acute rejection