Campath, Calcineurin Inhibitor Reduction and Chronic Allograft Nephropathy (3C)

Open-label, Randomised Multicentre Study of CAMPATH-1H Versus Basiliximab Induction Treatment and Sirolimus Versus Tacrolimus Maintenance Treatment for the Preservation of Renal Function in Patients Receiving Kidney Transplants

The 3C study is investigating whether reducing exposure to calcineurin inhibitors (by using more potent antibody induction treatment and/or an elective switch to sirolimus) can improve the function and survival of kidney transplants.

Study Overview

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

Detailed Description

The long-term survival of kidney transplants has not improved over the past decade despite reductions in the rate of acute rejection. The commonest cause of late graft loss is chronic allograft nephropathy which is frequently caused by calcineurin inhibitor toxicity. Therefore, it may be possible to improve long-term graft outcomes by reducing the amount of calcineurin inhibitor exposure.

Two possible strategies to do this were tested. Firstly, Campath-1H (a monoclonal lymphocyte-depleting antibody) was compared to standard basiliximab-based induction. All patients then received tacrolimus-based maintenance therapy for 6-months (using lower doses in the Campath-1H arm).

At six months, patients were re-randomized between remaining on tacrolimus and converting to sirolimus (and therefore no longer taking calcineurin inhibitors). Patients were then followed-up in clinic and through routine NHS registries to collect information on relevant outcomes (including graft function, survival, hospitalisations and death).

• Study Type: Interventional
• Enrollment (Actual): 852
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• United Kingdom
  • Birmingham, United Kingdom
    • University Hospitals Birmingham NHS Foundation Trust
  • Cambridge, United Kingdom
    • Addenbrooke's Hospital NHS Trust
  • Cardiff, United Kingdom
    • University Hospital of Wales
  • Coventry, United Kingdom
    • University Hospitals Coventry & Warwickshire
  • Edinburgh, United Kingdom
    • Royal Infirmary
  • Glasgow, United Kingdom
    • Western Infirmary
  • Hull, United Kingdom
    • Hull and East Yorkshire Hospitals NHS Trust
  • Leeds, United Kingdom
    • Leeds Teaching Hospitals NHS Trust
  • Liverpool, United Kingdom
    • Royal Liverpool and Broadgreen University Hospitals NHS Trust
  • London, United Kingdom
    • Royal Free Hampstead NHS Trust
  • London, United Kingdom
    • Kings College Hospital NHS Trust
  • London, United Kingdom
    • Bart's and the London NHS Trust
  • London, United Kingdom
    • Guy's and St Thomas's NHS Trust
  • Manchester, United Kingdom
    • Central Manchester NHS Trust
  • Newcastle, United Kingdom
    • Newcastle-upon-Tyne Hospitals NHS Trust
  • Nottingham, United Kingdom
    • Nottingham University Hospitals NHS Trust
  • Plymouth, United Kingdom
    • Plymouth Teaching Hospitals NHS Trust
  • Portsmouth, United Kingdom
    • Portsmouth Hospitals NHS Trust
  • Sheffield, United Kingdom
    • Sheffield teaching Hospitals NHS Trust
  • Oxon
    • Oxford, Oxon, United Kingdom, OX3 7LJ
      • Oxford Radcliffe Hospitals NHS Trust

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• men or women aged over 18 years
• recipient of kidney transplant (planned in next 24 hours)

Exclusion Criteria:

• recipients of multi-organ transplant
• previous treatment with Campath-1H
• active infection (including HIV, hepatitis B or C)
• history of anaphylaxis to humanized monoclonal antibody
• history of malignancy (except adequately treated non-melanoma skin cancer)
• loss of kidney transplant within 6 months not due to technical reasons
• medical history that might limit the individual's ability to take trial treatments for the duration of the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Alemtuzumab/Sirolimus; Induction therapy allocation: Alemtuzumab (Campath-1H). Maintenance therapy allocation (at 6-months post-transplant): Sirolimus	Drug: Alemtuzumab; Alemtuzumab 30 mg intravenously or subcutaneously, two doses 24 hours apart; Other Names: Campath-1H; Drug: Sirolimus; Sirolimus: target trough levels 6-12 ng/mL for first 6-months after maintenance therapy randomization, then 5-10 ng/mL; Other Names: Rapamune
Experimental: Alemtuzumab/Tacrolimus; Induction therapy allocation: Alemtuzumab (Campath-1H). Maintenance therapy allocation (at 6-months post-transplant): Tacrolimus	Drug: Alemtuzumab; Alemtuzumab 30 mg intravenously or subcutaneously, two doses 24 hours apart; Other Names: Campath-1H; Drug: Tacrolimus; Tacrolimus: target trough levels 5-7 ng/mL after maintenance therapy randomization.; Other Names: Prograf
Active Comparator: Basiliximab/Tacrolimus; Induction therapy allocation: Basiliximab. Maintenance therapy allocation (at 6-months post-transplant): Tacrolimus	Drug: Tacrolimus; Tacrolimus: target trough levels 5-7 ng/mL after maintenance therapy randomization.; Other Names: Prograf; Drug: Basiliximab; 20 mg intravenously, two doses 96 hours apart; Other Names: Simulect
Active Comparator: Basiliximab/Sirolimus; Induction therapy allocation: Basiliximab. Maintenance therapy allocation (at 6-months post-transplant): Sirolimus	Drug: Sirolimus; Sirolimus: target trough levels 6-12 ng/mL for first 6-months after maintenance therapy randomization, then 5-10 ng/mL; Other Names: Rapamune; Drug: Basiliximab; 20 mg intravenously, two doses 96 hours apart; Other Names: Simulect

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Biopsy-proven Acute Rejection at 6-months After Randomization to Induction Therapy	Occurence of biopsy-proven acute rejection events at 6-months after transplantation during Period 1 (randomization to induction therapy (Campath-1H and Tacrolimus, or Basiliximab and Tacrolimus))	6 months post-transplantation
Graft Function (at 18-months After Randomization to Maintenance Therapy)	Estimated glomerular filtration rate (estimated using MDRD formula) at 18-months after maintenance therapy randomization to either Sirolimus or Tacrolimus.	2 years post-transplantation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Graft Failure (at 6-months After Randomization to Induction Therapy)	Return to dialysis or re-transplantation by 6-months after randomization to induction therapy.	6 months post-transplantation
Number of Participants With Graft Failure (at 18-Months After Randomization to Maintenance Therapy)	Return to dialysis or re-transplantation by 18-months after randomization to maintenance therapy.	2 years post-transplantation
Number of Participants With Serious Infection (at 6-months After Randomization to Induction Therapy)	Occurrence of any serious infection (opportunistic or requiring admission to hospital) reported within Period 1 (randomization to induction therapy of either Alemtuzumab (Campath-1H) and Tacrolimus, or Basiliximab and Tacrolimus).	6-months post-transplantation
Number of Participants With Serious Infection (at 18-months After Randomization to Maintenance Therapy)	Occurrence of any serious infection (opportunistic or requiring admission to hospital) reported during Period 2 (maintenance therapy randomization to either Sirolimus or Tacrolimus).	2 years post-transplantation
Number of Participants With Cancer (at 18-months After Randomization to Maintenance Therapy)	Occurrence of any cancer reported during Period 2 (maintenance therapy randomization to either Sirolimus or Tacrolimus).	2 years post-transplantation
Number of Participants With Major Vascular Event (at 18-months After Randomization to Maintenance Therapy)	Composite of non-fatal myocardial infarction, non-fatal stroke, cardiovascular death or arterial revascularization	2 years post-transplantation

Collaborators and Investigators

• Sponsor: University of Oxford
• Collaborators: Novartis; Pfizer; National Health Service, United Kingdom
• Investigators: Study Director: Peter Friend, University of Oxford; Principal Investigator: Colin Baigent, University of Oxford; Principal Investigator: Martin J Landray, University of Oxford; Principal Investigator: Paul Harden, University of Oxford; Principal Investigator: Richard Haynes, University of Oxford

Publications and helpful links

General Publications

• 3C Study Collaborative Group; Haynes R, Harden P, Judge P, Blackwell L, Emberson J, Landray MJ, Baigent C, Friend PJ. Alemtuzumab-based induction treatment versus basiliximab-based induction treatment in kidney transplantation (the 3C Study): a randomised trial. Lancet. 2014 Nov 8;384(9955):1684-90. doi: 10.1016/S0140-6736(14)61095-3. Epub 2014 Jul 28.
• 3C Study Collaborative Group. Campath, calcineurin inhibitor reduction, and chronic allograft nephropathy (the 3C Study) - results of a randomized controlled clinical trial. Am J Transplant. 2018 Jun;18(6):1424-1434. doi: 10.1111/ajt.14619. Epub 2018 Jan 9.
• Haynes R, Baigent C, Harden P, Landray M, Akyol M, Asderakis A, Baxter A, Bhandari S, Chowdhury P, Clancy M, Emberson J, Gibbs P, Hammad A, Herrington W, Jayne K, Jones G, Krishnan N, Lay M, Lewis D, Macdougall I, Nathan C, Neuberger J, Newstead C, Pararajasingam R, Puliatti C, Rigg K, Rowe P, Sharif A, Sheerin N, Sinha S, Watson C, Friend P; 3C Study Collaborative Group. Campath, calcineurin inhibitor reduction and chronic allograft nephropathy (3C) study: background, rationale, and study protocol. Transplant Res. 2013 May 6;2(1):7. doi: 10.1186/2047-1440-2-7.

Helpful Links

• 3C study website

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2010
• Primary Completion (Actual): February 1, 2014
• Study Completion (Actual): March 1, 2020

Study Registration Dates

• First Submitted: May 6, 2010
• First Submitted That Met QC Criteria: May 6, 2010
• First Posted (Estimate): May 10, 2010

Study Record Updates

• Last Update Posted (Actual): April 2, 2020
• Last Update Submitted That Met QC Criteria: March 23, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Keywords: Tacrolimus; Sirolimus; Kidney transplantation; Alemtuzumab; Campath-1H; Basiliximab
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Immunological; Anti-Bacterial Agents; Antibiotics, Antineoplastic; Antifungal Agents; Calcineurin Inhibitors; Tacrolimus; Sirolimus; Basiliximab; Alemtuzumab
• Other Study ID Numbers: CTSU3C1; 2008-008553-27 (EudraCT Number); ISRCTN88894088 (Registry Identifier: ISRCTN)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Proposals for substudies must be approved by the Steering Committee. Procedure for accessing the data for this study are available on https://www.ndph.ox.ac.uk/data-access
• IPD Sharing Access Criteria: See URL
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP