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

Phase 3

Completed

• Conditions: Kidney Transplantation
• Interventions: Drug: Alemtuzumab; Drug: Tacrolimus

• Registration Number: NCT00147381
• Lead Sponsor: Dr. Claudia Bösmüller

Brief Summary

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

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.

Study Timeline

• Study Start: 2004-01
• Study First Submitted: 2005-09-06
• Study First Submitted QC: 2005-09-06
• Study First Posted: 2005-09-07
• Primary Completion: 2008-08
• Study Completion: 2011-07
• Status Verified: 2012-06
• Last Update Submitted: 2012-06-18
• Last Update Posted: 2012-06-19

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 197

Inclusion Criteria

• age 18-65
• endstage renal failure with no previous renal transplantation
• cadaveric donor
• written informed consent

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Campath-1H 20 mg	Alemtuzumab	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.
Tacrolimus	Tacrolimus	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.
Campath-1H 30 mg	Alemtuzumab	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.

Primary Outcome Measures

Name	Time	Method
Biopsy proven acute rejection episodes 6 months after transplantation (Banff Classification)	Month 6

Secondary Outcome Measures

Name	Time	Method
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

Trial Locations

Locations (1)

University Hospital Innsbruck; 🇦🇹 Innsbruck, Tyrol, Austria