Campath, Calcineurin Inhibitor Reduction and Chronic Allograft Nephropathy

Kidney Transplantation Clinical Trial

— 3C  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01120028
• Other study ID #: CTSU3C1
• Secondary ID: 2008-008553-27IS
• Status: Completed
• Phase: Phase 2/Phase 3
• Start date: September 2010
• Est. completion date: March 2020

Study information

• Verified date: March 2020
• Source: University of Oxford
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 852
• Est. completion date: March 2020
• Est. primary completion date: February 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Kidney Transplantation

Intervention

Drug:
• Alemtuzumab
Alemtuzumab 30 mg intravenously or subcutaneously, two doses 24 hours apart
• Basiliximab
20 mg intravenously, two doses 96 hours apart
• Sirolimus
Sirolimus: target trough levels 6-12 ng/mL for first 6-months after maintenance therapy randomization, then 5-10 ng/mL
• Tacrolimus
Tacrolimus: target trough levels 5-7 ng/mL after maintenance therapy randomization.

Locations

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

Sponsors (4)

Lead Sponsor	Collaborator
University of Oxford	National Health Service, United Kingdom, Novartis, Pfizer

Country where clinical trial is conducted

United Kingdom, 

References & Publications (2)

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 — View Citation

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 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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

External Links

•   3C study website