CamTac Trial:Campath-Tacrolimus vs IL2R MoAb/Tacrolimus/MMF in Renal Transplantation

A Randomised Controlled Comparison of Campath-Tacrolimus vs IL2R MoAb-Tacrolimus/Mycophenolate Mofetil in Kidney Transplantation

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.

Study Overview

• Status: Completed
• Conditions: Kidney Diseases; Kidney Transplantation; Kidney Failure
• Intervention / Treatment: Drug: Campath; Drug: Daclizumab

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.

• Study Type: Interventional
• Enrollment (Actual): 123
• Phase: Phase 4

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom, W12 OHS
    • West London Renal and Transplant Centre, 4th Floor Ham House, Hammersmith Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Campath-Tacrolimus; Campath induction with 7-day short-course steroids followed by tacrolimus monotherapy	Drug: Campath; Monoclonal antibody induction therapy; Other Names: Alemtuzumab
Experimental: Daclizumab-Tacrolimus-Mycophenolate; Daclizumab induction with 7-day short-course steroids followed by Tacrolimus and Mycophenolate mofetil therapy	Drug: Daclizumab; Monoclonal antibody induction therapy; Other Names: Zinbryta

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
One Year Survival With a Functioning Graft	One year survival with a functioning graft, defined as transplant recipient remaining alive and dialysis-independent. the functioning graft is a graft still functioning at the time of analysis. Graft function was estimated using the Modification of Diet in Renal Disease four-variable formula and comparison of graft function between arms undertaken with Student'st test.	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Occurrence of Rejection Episodes	Biopsy-proven rejection episodes classified using Banff criteria	1 year
Occurrence of Significant Episodes of Infection	Occurence of infection of sufficient severity to produce positive cultures or Nucleic-acid test results from blood, urine, or other body fluids	1 year
Initial Length of Stay in Hospital		1 year
Presence in the Blood of Cells Which Might Trigger Rejection in, or Promote Tolerance to the Graft		3 years
Early Development of Scarring in the Grafts	Biopsy proven Calcineurin Inhibitor (CNI) toxicity free survival	1 year
Graft Function: Level of Creatinine		2 years
Patient Survival Censored for Death With Function	Cumulative patient survival	2 years
Graft Survival Censored for Death With Function	Graft survival (defined as grafts maintaining dialysis independence)	2 years

Collaborators and Investigators

• Sponsor: EMagnusson
• Investigators: Principal Investigator: Adam G McLean, FRCP, DPhil, Hammersmith Hospital NHS Trust; Study Director: David H Taube, MBBCh, FRCP, Hammersmith Hospital NHS Trust

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2005
• Primary Completion (Actual): June 1, 2011
• Study Completion (Actual): June 1, 2011

Study Registration Dates

• First Submitted: October 28, 2005
• First Submitted That Met QC Criteria: October 28, 2005
• First Posted (Estimate): October 30, 2005

Study Record Updates

• Last Update Posted (Actual): September 29, 2021
• Last Update Submitted That Met QC Criteria: September 1, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Keywords: Kidney Transplantation; Kidney Disease; Kidney Failure; Graft Rejection
• Additional Relevant MeSH Terms: Urologic Diseases; Kidney Diseases; Renal Insufficiency; Physiological Effects of Drugs; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Immunological; Alemtuzumab; Daclizumab
• Other Study ID Numbers: SMHREN0501; 2005-002856-17 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No