CamTac Trial:Campath-Tacrolimus vs IL2R MoAb/Tacrolimus/MMF in Renal Transplantation
Condition: Kidney Transplantation; Kidney Diseases; Kidney Failure
MeSH terms: Kidney Diseases; Renal Insufficiency
Study type: Interventional
Phase: Phase 4

Summary: 
      The advent of new, potent immunosuppressive (anti-rejection) drugs over the past ten years
      has substantially reduced the risk of rejection after kidney transplantation, has allowed the
      development of immuno-suppressive regimens that do not use long-term steroids (steroid
      avoidance), and has improved transplant success rates both in the short and medium term.

      The main new agents used in these modern regimens are the calcineurin inhibitor (CNI)
      tacrolimus; the anti-proliferative agent mycophenolate; and induction agents which are used
      to provide effective early suppression of the rejection process; these include monoclonal
      antibodies (MoAb) such as IL-2 receptor blocking antibodies (IL-2R MoAb: basiliximab and
      daclizumab) and the anti-CD52 antibody Campath-1H (alemtuzumab).

      Although almost all modern immunosuppressive regimens involve one or more of these agents, it
      is not known which is the safest and most effective combination.

      This randomised controlled trial compares two steroid sparing regimens which have been used
      with very good short and medium term results at St Mary's Hospital Renal and Transplant Unit
      over the last 5 years. The primary hypothesis is that the alemtuzumab/tacrolimus regimen is
      as effective and safe as the IL-2R MoAb/tacrolimus/mycophenolate regimen.
    

Detailed description: 
      RECENT EXPERIENCE AT ST MARY'S:

      The St Mary's Hospital Renal Unit (now combined with the Hammersmith Hospital Renal Unit at
      the West London Renal and Transplant Centre) introduced Tacrolimus based immunosuppression in
      1995, developing a steroid avoidance regimen based on Tacrolimus, Mycophenolate, and IL-2R
      MoAb between 2000 and 2002, and moving to Campath-1H as an induction agent in 2004. Results
      over this period have been excellent with five and ten year survivals with functioning graft
      rates of 82% and 72% for the first 260 cadaveric kidney transplants performed since 1995.

      The two most recent regimens used at St Mary's have both produced very low (< 10%) rejection
      rates, and very good (> 90%) short-term rejection-free patient and graft survival rates.
      Between 2002 and 2004, the regimen consisted of induction with an Interleukin-2 (IL2)
      -Receptor blocking monoclonal antibody with Tacrolimus and Mycophenolate as long term
      maintenance therapy. In patients without rejection steroid usage was limited to the first 7
      days post-transplant. The current regimen uses Campath-1H (which is now well established as
      an induction agent in renal transplantation for induction), with Tacrolimus monotherapy
      maintenance and an identical short-course steroid regimen.

      CHARACTERISTICS OF THE TWO REGIMENS TO BE COMPARED:

      The IL2R MoAb/Tacrolimus/Mycophenolate/Short-course steroids regimen (2002-2004 Regimen 1)
      has the advantage of flexibility in terms of adjusting maintenance therapy to allow clinical
      response to patients and transplants with different tolerance of the two maintenance agents,
      but involves increased expense in terms of using and monitoring the blood levels of two
      modern (and hence expensive) agents. In addition, patients have long-term exposure to the
      anti-proliferative agent Mycophenolate, which can be associated with increased risk of
      infection, gastrointestinal side effects, and skin malignancies.

      The Campath-1H/Tacrolimus/Short-course steroids regimen (2004-current, Regimen 2) has the
      advantage of highly effective immunosuppression in the initial 3-month period, allowing lower
      doses of the potentially nephrotoxic Tacrolimus to be used, and simplicity, but exposes
      patients to a period of several months of lymphopenia (reduced lymphocyte counts in the
      blood) after Campath administration, and reliance on Tacrolimus monotherapy for maintenance
      which might lead to greater long term Tacrolimus exposure.

      PROPOSED STUDY:

      In order to allow a proper comparison of these two anti-rejection treatment combinations we
      propose a randomised trial which will enable us to consider the relative merits of the two
      regimens without the introduction of bias associated with using historical control groups.
      Transplant recipients will be randomised in a 1:2 ratio to regimen 1 and regimen 2.
    

Intervention name(s): Campath; Daclizumab
Intervention type(s): Drug; Drug
Intervention description(s): Monoclonal antibody induction therapy; Monoclonal antibody induction therapy
Other intervention name(s): Alemtuzumab; Zinbryta
Intervention MeSH terms: Alemtuzumab; Daclizumab
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Prevention
Keywords: Kidney Transplantation; Kidney Disease; Kidney Failure; Graft Rejection