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

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

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).

Study Overview

• Status: Completed
• Conditions: Kidney Transplantation
• Intervention / Treatment: Drug: Alemtuzumab; Drug: Alemtuzumab; Drug: Tacrolimus

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 Type: Interventional
• Enrollment (Actual): 197
• Phase: Phase 3

Contacts and Locations

Study Locations

• Austria
  • Tyrol
    • Innsbruck, Tyrol, Austria, 6020
      • University Hospital Innsbruck

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Campath-1H 20 mg; 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; Day 0: Campath-1H 20 mg IV infusion over 3-6 hours Day 1: Campath-1H 20 mg IV infusion over 3-6 hours; Other Names: MABCAMPATH; Drug: Alemtuzumab; Day 0: Campath-1H 30 mg IV infusion over 3-6 hours Day 1: Campath-1H 30 mg IV infusion over 3-6 hours; Other Names: MABCAMPATH
ACTIVE_COMPARATOR: 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.	Drug: Tacrolimus; 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.; Other Names: Prograf; Advagraf
EXPERIMENTAL: Campath-1H 30 mg; 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; Day 0: Campath-1H 20 mg IV infusion over 3-6 hours Day 1: Campath-1H 20 mg IV infusion over 3-6 hours; Other Names: MABCAMPATH; Drug: Alemtuzumab; Day 0: Campath-1H 30 mg IV infusion over 3-6 hours Day 1: Campath-1H 30 mg IV infusion over 3-6 hours; Other Names: MABCAMPATH

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Dr. Claudia Bösmüller
• Collaborators: Astellas Pharma GmbH
• Investigators: Principal Investigator: Raimund Margreiter, Prof. Dr., Medical University for Surgery and Transplantation, Innsbruck

Publications and helpful links

General Publications

• Calne R, Moffatt SD, Friend PJ, Jamieson NV, Bradley JA, Hale G, Firth J, Bradley J, Smith KG, Waldmann H. Campath IH allows low-dose cyclosporine monotherapy in 31 cadaveric renal allograft recipients. Transplantation. 1999 Nov 27;68(10):1613-6. doi: 10.1097/00007890-199911270-00032.
• Margreiter R, Klempnauer J, Neuhaus P, Muehlbacher F, Boesmueller C, Calne RY. Alemtuzumab (Campath-1H) and tacrolimus monotherapy after renal transplantation: results of a prospective randomized trial. Am J Transplant. 2008 Jul;8(7):1480-5. doi: 10.1111/j.1600-6143.2008.02273.x.

Study record dates

Study Major Dates

• Study Start: January 1, 2004
• Primary Completion (ACTUAL): August 1, 2008
• Study Completion (ACTUAL): July 1, 2011

Study Registration Dates

• First Submitted: September 6, 2005
• First Submitted That Met QC Criteria: September 6, 2005
• First Posted (ESTIMATE): September 7, 2005

Study Record Updates

• Last Update Posted (ESTIMATE): June 19, 2012
• Last Update Submitted That Met QC Criteria: June 18, 2012
• Last Verified: June 1, 2012

More Information

Terms related to this study

• Keywords: immunosuppression; Tacrolimus; Alemtuzumab; Campath-1H; renal transplantation; prevention of acute rejection
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Immunological; Calcineurin Inhibitors; Tacrolimus; Alemtuzumab
• Other Study ID Numbers: TaCam 07_MC; DE-02-RG-121/Margreiter