Clinical trial NCT00246129: CamTac Trial:Campath-Tacrolimus vs IL2R MoAb/Tacrolimus/MMF in Renal Transplantation
Official title: A Randomised Controlled Comparison of Campath-Tacrolimus vs IL2R MoAb-Tacrolimus/Mycophenolate Mofetil in Kidney Transplantation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Kidney Transplantation
Kidney Diseases
Kidney Failure
Keywords: Kidney Transplantation
Kidney Disease
Kidney Failure
Graft Rejection
Lead sponsor: Imperial College Healthcare NHS Trust
Sponsor class: OTHER
First posted: 2005-10-30
Enrollment: 123
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief 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.

Eligibility criteria: Inclusion Criteria:

* Kidney transplant recipients under the care of the West London Renal and Transplant Centre

Exclusion Criteria:

* Patients who are unable to give written informed consent
* Simultaneous kidney/pancreas transplant recipients
* Non-heart beating deceased donor transplant recipients
* Patients who would not be offered Campath-1H induction under our current protocol (patients with previous malignancy or with previous exposure to cytotoxic or antiproliferative agents)

Primary outcomes:
measure: One Year Survival With a Functioning Graft
timeFrame: 1 year
Secondary outcomes:
measure: Occurrence of Rejection Episodes
timeFrame: 1 year
measure: Occurrence of Significant Episodes of Infection
timeFrame: 1 year
measure: Initial Length of Stay in Hospital
timeFrame: 1 year
measure: Presence in the Blood of Cells Which Might Trigger Rejection in, or Promote Tolerance to the Graft
timeFrame: 3 years
measure: Early Development of Scarring in the Grafts
timeFrame: 1 year
measure: Graft Function: Level of Creatinine
timeFrame: 2 years
measure: Patient Survival Censored for Death With Function
timeFrame: 2 years
measure: Graft Survival Censored for Death With Function
timeFrame: 2 years
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: West London Renal and Transplant Centre, 4th Floor Ham House, Hammersmith Hospital
Study officials:
affiliation: Hammersmith Hospital NHS Trust
name: Adam G McLean, FRCP, DPhil
role: PRINCIPAL_INVESTIGATOR
affiliation: Hammersmith Hospital NHS Trust
name: David H Taube, MBBCh, FRCP
role: STUDY_DIRECTOR
References:
citation: Loucaidou M, McLean AG, Cairns TD, Griffith M, Hakim N, Palmer A, Papalois V, Van Tromp J, Loucaides C, Welsh KI, Taube D. Five-year results of kidney transplantation under tacrolimus-based regimes: the persisting significance of vascular rejection. Transplantation. 2003 Oct 15;76(7):1120-3. doi: 10.1097/01.TP.0000076474.76480.A4.
citation: Borrows R, Loucaidou M, Van Tromp J, Cairns T, Griffith M, Hakim N, McLean A, Palmer A, Papalois V, Taube D. Steroid sparing with tacrolimus and mycophenolate mofetil in renal transplantation. Am J Transplant. 2004 Nov;4(11):1845-51. doi: 10.1111/j.1600-6143.2004.00583.x.
citation: Borrows R, Loucaidou M, Van Tromp J, Singh S, Cairns T, Griffith M, Hakim N, McLean A, Palmer A, Papalois V, Taube D. Steroid sparing in renal transplantation with tacrolimus and mycophenolate mofetil: three-year results. Transplant Proc. 2005 May;37(4):1792-4. doi: 10.1016/j.transproceed.2005.03.150.
citation: Chan K, Taube D, Roufosse C, Cook T, Brookes P, Goodall D, Galliford J, Cairns T, Dorling A, Duncan N, Hakim N, Palmer A, Papalois V, Warrens AN, Willicombe M, McLean AG. Kidney transplantation with minimized maintenance: alemtuzumab induction with tacrolimus monotherapy--an open label, randomized trial. Transplantation. 2011 Oct 15;92(7):774-80. doi: 10.1097/TP.0b013e31822ca7ca.