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

• Sponsor: EMagnusson (Other)
• Overall Status: Completed
• CT.gov ID: NCT00246129
• Collaborator: (none)
• Enrollment: 123
• Location: 1
• Arms: 2
• Actual Duration (Months): 68
• Patients Per Site Per Month: 1.8

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Kidney Transplantation; Kidney Diseases; Kidney Failure	Drug: Campath; Drug: Daclizumab	Phase 4

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 Design

• Study Type: Interventional
• Actual Enrollment: 123 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: A Randomised Controlled Comparison of Campath-Tacrolimus vs IL2R MoAb-Tacrolimus/Mycophenolate Mofetil in Kidney Transplantation
• Actual Study Start Date: Oct 1, 2005
• Actual Primary Completion Date: Jun 1, 2011
• Actual Study Completion Date: Jun 1, 2011

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. One Year Survival With a Functioning Graft [1 year]

   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.

Secondary Outcome Measures

1. Occurrence of Rejection Episodes [1 year]

   Biopsy-proven rejection episodes classified using Banff criteria

2. Occurrence of Significant Episodes of Infection [1 year]

   Occurence of infection of sufficient severity to produce positive cultures or Nucleic-acid test results from blood, urine, or other body fluids

3. Initial Length of Stay in Hospital [1 year]

4. Presence in the Blood of Cells Which Might Trigger Rejection in, or Promote Tolerance to the Graft [3 years]

5. Early Development of Scarring in the Grafts [1 year]

   Biopsy proven Calcineurin Inhibitor (CNI) toxicity free survival

6. Graft Function: Level of Creatinine [2 years]

7. Patient Survival Censored for Death With Function [2 years]

   Cumulative patient survival

8. Graft Survival Censored for Death With Function [2 years]

   Graft survival (defined as grafts maintaining dialysis independence)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	West London Renal and Transplant Centre, 4th Floor Ham House, Hammersmith Hospital	London		United Kingdom	W12 OHS

Sponsors and Collaborators

• EMagnusson

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

• 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.
• 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.
• 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.

• Responsible Party: EMagnusson, RIO, Imperial College Healthcare NHS Trust
• ClinicalTrials.gov Identifier: NCT00246129
• Other Study ID Numbers: SMHREN0501; 2005-002856-17
• First Posted: Oct 30, 2005
• Last Update Posted: Sep 29, 2021
• Last Verified: Sep 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by EMagnusson, RIO, Imperial College Healthcare NHS Trust: Kidney Transplantation; Kidney Disease; Kidney Failure; Graft Rejection
• Additional relevant MeSH terms: Kidney Diseases; Renal Insufficiency; Alemtuzumab; Daclizumab

Study Results

Participant Flow

Arm/Group Title	Campath-Tacrolimus	Daclizumab-Tacrolimus-Mycophenolate
Arm/Group Description	Campath (1x30mg) induction with 7-day short-course steroids followed by tacrolimus monotherapy (dose adjusted to target trough level 9-11ng/ml)	Daclizumab 2mg/kg x2 days 0+14) induction with 7-day short-course steroids followed by Tacrolimus (adjusted to target trough 9-11ng/ml) and Mycophenolate mofetil therapy (750mg bd)
Period Title: Overall Study
STARTED	82	41
COMPLETED	75	39
NOT COMPLETED	7	2

Baseline Characteristics

Arm/Group Title	Campath-Tacrolimus	Daclizumab-Tacrolimus-Mycophenolate	Total
Arm/Group Description	Campath induction with 7-day short-course steroids followed by tacrolimus monotherapy	Daclizumab induction with 7-day short-course steroids followed by Tacrolimus and Mycophenolate mofetil therapy	Total of all reporting groups
Overall Participants	82	41	123
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	77 93.9%	39 95.1%	116 94.3%
>=65 years	5 6.1%	2 4.9%	7 5.7%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	47.3 (13.4)	47.0 (10.6)	47.2 (12.5)
Sex: Female, Male (Count of Participants)
Female	28 34.1%	14 34.1%	42 34.1%
Male	54 65.9%	27 65.9%	81 65.9%
Region of Enrollment (participants) [Number]
United Kingdom	82 100%	41 100%	123 100%

Outcome Measures

1. Primary Outcome

Title	One Year Survival With a Functioning Graft
Description	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.
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Campath-Tacrolimus	Daclizumab-Tacrolimus-Mycophenolate
Arm/Group Description	Campath induction with 7-day short-course steroids followed by tacrolimus monotherapy	Daclizumab induction with 7-day short-course steroids followed by Tacrolimus and Mycophenolate mofetil therapy
Measure Participants	82	41
Number (90% Confidence Interval) [Percent of patients]	97.6	95.1

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Campath-Tacrolimus, Daclizumab-Tacrolimus-Mycophenolate
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.467
	Comments
	Method	Log Rank
	Comments

2. Secondary Outcome

Title	Occurrence of Rejection Episodes
Description	Biopsy-proven rejection episodes classified using Banff criteria
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Campath Tacrolimus	Daclizumab-Tacrolimus-Mycophenolate
Arm/Group Description	Alemtuzumab induction with short-course steroids and Tacrolimus maintenance monotherapy
Measure Participants	82	41
Number (90% Confidence Interval) [Percentage of patients]	91.2	82.3

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Campath-Tacrolimus, Daclizumab-Tacrolimus-Mycophenolate
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.138
	Comments
	Method	Log Rank
	Comments

3. Secondary Outcome

Title	Occurrence of Significant Episodes of Infection
Description	Occurence of infection of sufficient severity to produce positive cultures or Nucleic-acid test results from blood, urine, or other body fluids
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Campath-Tacrolimus	Daclizumab-Tacrolimus-Mycophenolate
Arm/Group Description	Campath induction with 7-day short-course steroids followed by tacrolimus monotherapy	Daclizumab induction with 7-day short-course steroids followed by Tacrolimus and Mycophenolate mofetil therapy
Measure Participants	82	41
Number [# of occurrences per 100 patient years]	73	76

4. Secondary Outcome

Title	Initial Length of Stay in Hospital
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Campath-Tacrolimus	Daclizumab-Tacrolimus-Mycophenolate
Arm/Group Description	Campath induction with 7-day short-course steroids followed by tacrolimus monotherapy	Daclizumab induction with 7-day short-course steroids followed by Tacrolimus and Mycophenolate mofetil therapy
Measure Participants	82	41
Mean (Standard Deviation) [Days]	11.7 (6.4)	12.1 (7.6)

5. Secondary Outcome

Title	Presence in the Blood of Cells Which Might Trigger Rejection in, or Promote Tolerance to the Graft
Time Frame	3 years

Outcome Measure Data

Analysis Population Description

Data not collected

Arm/Group Title	Campath Tacrolimus '	Daclizumab-Tacrolimus-Mycophenolate
Arm/Group Description
Measure Participants	0	0

6. Secondary Outcome

Title	Early Development of Scarring in the Grafts
Description	Biopsy proven Calcineurin Inhibitor (CNI) toxicity free survival
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Campath-Tacrolimus	Daclizumab-Tacrolimus-Mycophenolate
Arm/Group Description	Campath induction with 7-day short-course steroids followed by tacrolimus monotherapy	Daclizumab induction with 7-day short-course steroids followed by Tacrolimus and Mycophenolate mofetil therapy
Measure Participants	82	41
Number [Percentage of participants with no scar]	96 117.1%	90 219.5%

7. Secondary Outcome

Title	Graft Function: Level of Creatinine
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Campath-Tacrolimus	Daclizumab-Tacrolimus-Mycophenolate
Arm/Group Description	Campath induction with 7-day short-course steroids followed by tacrolimus monotherapy	Daclizumab induction with 7-day short-course steroids followed by Tacrolimus and Mycophenolate mofetil therapy
Measure Participants	82	41
Mean (Standard Deviation) [mmol/L]	127.3 (36.2)	147.0 (69.1)

8. Secondary Outcome

Title	Patient Survival Censored for Death With Function
Description	Cumulative patient survival
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Campath-Tacrolimus	Daclizumab-Tacrolimus-Mycophenolate
Arm/Group Description	Campath induction with 7-day short-course steroids followed by tacrolimus monotherapy	Daclizumab induction with 7-day short-course steroids followed by Tacrolimus and Mycophenolate mofetil therapy
Measure Participants	82	41
Number [Percentage of transplant recipients]	98	98

9. Secondary Outcome

Title	Graft Survival Censored for Death With Function
Description	Graft survival (defined as grafts maintaining dialysis independence)
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Campath-Tacrolimus	Daclizumab-Tacrolimus-Mycophenolate
Arm/Group Description	Campath induction with 7-day short-course steroids followed by tacrolimus monotherapy	Daclizumab induction with 7-day short-course steroids followed by Tacrolimus and Mycophenolate mofetil therapy
Measure Participants	82	41
Number [Percentage of grafts]	91	95

Adverse Events

Time Frame	1 year
Arm/Group Title	Campath-Tacrolimus		Daclizumab-Tacrolimus-Mycophenolate
Arm/Group Description	Campath induction with 7-day short-course steroids followed by tacrolimus monotherapy		Daclizumab induction with 7-day short-course steroids followed by Tacrolimus and Mycophenolate mofetil therapy
All Cause Mortality
	Campath-Tacrolimus		Daclizumab-Tacrolimus-Mycophenolate
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/82 (2.4%)		1/41 (2.4%)
Serious Adverse Events
	Campath-Tacrolimus		Daclizumab-Tacrolimus-Mycophenolate
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/82 (6.1%)		5/41 (12.2%)
Blood and lymphatic system disorders
Immune thrombocytopenic purpura	1/82 (1.2%)	1	0/41 (0%)	0
Metabolism and nutrition disorders
New-onset diabetes after transplantation	4/82 (4.9%)	4	5/41 (12.2%)	5
Other (Not Including Serious) Adverse Events
	Campath-Tacrolimus		Daclizumab-Tacrolimus-Mycophenolate
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	59/82 (72%)		30/41 (73.2%)
Infections and infestations
Urinary tract infection	31/82 (37.8%)	31	9/41 (22%)	9
Bacteremia	15/82 (18.3%)	15	9/41 (22%)	9
Wound infection	6/82 (7.3%)	6	6/41 (14.6%)	6
Cytomegalovirus infection	1/82 (1.2%)	1	4/41 (9.8%)	4
Other infection	6/82 (7.3%)	6	2/41 (4.9%)	2

Limitations/Caveats

Our trial was conservatively powered to detect a large difference in survival with a functioning graft at 1 year, so we are not able to exclude the possibility of small differences, the single-centre nature of the study may limit it's applicability.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.