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

This study has been completed.
Sponsor:
Collaborator:
Astellas Pharma GmbH
Information provided by (Responsible Party):
Dr. Claudia Bösmüller, Medical University Innsbruck
ClinicalTrials.gov Identifier:
NCT00147381
First received: September 6, 2005
Last updated: June 18, 2012
Last verified: June 2012
  Purpose

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).


Condition Intervention Phase
Kidney Transplantation
Drug: Alemtuzumab
Drug: Tacrolimus
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Medical University Innsbruck:

Primary Outcome Measures:
  • Biopsy proven acute rejection episodes 6 months after transplantation (Banff Classification) [ Time Frame: Month 6 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Biopsy proven acute rejection episodes 12 months after transplantation (Banff Classification) [ Time Frame: Year 1 ] [ Designated as safety issue: Yes ]
  • Time to 1st biopsy proven acute rejection episode (Banff Cl.) [ Time Frame: Year 1 ] [ Designated as safety issue: No ]
  • Patient and graft survival [ Time Frame: Year 1 ] [ Designated as safety issue: No ]
  • Number of patients who will get antilymphocyte preparation for treatment of steroid resistant acute rejection episodes [ Time Frame: Year 1 ] [ Designated as safety issue: No ]
  • Treatment failure defined as change from immunosuppressive protocol because of biopsy proven intractable rejection [ Time Frame: Year 1 ] [ Designated as safety issue: No ]
  • Adverse events (e.g. infections, PTLD) [ Time Frame: Year 1 ] [ Designated as safety issue: No ]
  • Creatinine clearance [ Time Frame: Year 1 ] [ Designated as safety issue: No ]

Enrollment: 197
Study Start Date: January 2004
Study Completion Date: July 2011
Primary Completion Date: August 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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 30 mg IV infusion over 3-6 hours

Day 1: Campath-1H 30 mg IV infusion over 3-6 hours

Other Name: MABCAMPATH

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.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00147381

Locations
Austria
University Hospital Innsbruck
Innsbruck, Tyrol, Austria, 6020
Sponsors and Collaborators
Dr. Claudia Bösmüller
Astellas Pharma GmbH
Investigators
Principal Investigator: Raimund Margreiter, Prof. Dr. Medical University for Surgery and Transplantation, Innsbruck
  More Information

Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Dr. Claudia Bösmüller, Dr. med., Medical University Innsbruck
ClinicalTrials.gov Identifier: NCT00147381     History of Changes
Other Study ID Numbers: TaCam 07_MC, DE-02-RG-121/Margreiter
Study First Received: September 6, 2005
Last Updated: June 18, 2012
Health Authority: Austria: Federal Office for Safety in Health Care

Keywords provided by Medical University Innsbruck:
Campath-1H
Alemtuzumab
Tacrolimus
renal transplantation
immunosuppression
prevention of acute rejection

Additional relevant MeSH terms:
Tacrolimus
Alemtuzumab
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on September 18, 2014