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Campath, Calcineurin Inhibitor Reduction and Chronic Allograft Nephropathy

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

Status
Completed
Phases
Phase 2Phase 3
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT01120028
Acronym
3C
Enrollment
852
Registered
2010-05-10
Start date
2010-09-30
Completion date
2020-03-31
Last updated
2020-04-02

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Kidney Transplantation

Keywords

Kidney transplantation, Alemtuzumab, Sirolimus, Basiliximab, Tacrolimus, Campath-1H

Brief 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.

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).

Interventions

DRUGAlemtuzumab

Alemtuzumab 30 mg intravenously or subcutaneously, two doses 24 hours apart

DRUGBasiliximab

20 mg intravenously, two doses 96 hours apart

DRUGSirolimus

Sirolimus: target trough levels 6-12 ng/mL for first 6-months after maintenance therapy randomization, then 5-10 ng/mL

DRUGTacrolimus

Tacrolimus: target trough levels 5-7 ng/mL after maintenance therapy randomization.

Sponsors

National Health Service, United Kingdom
CollaboratorOTHER_GOV
Pfizer
CollaboratorINDUSTRY
Novartis
CollaboratorINDUSTRY
University of Oxford
Lead SponsorOTHER

Study design

Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
TREATMENT
Masking
NONE

Eligibility

Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No

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

Design outcomes

Primary

MeasureTime frameDescription
Number of Participants With Biopsy-proven Acute Rejection at 6-months After Randomization to Induction Therapy6 months post-transplantationOccurence 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))
Graft Function (at 18-months After Randomization to Maintenance Therapy)2 years post-transplantationEstimated glomerular filtration rate (estimated using MDRD formula) at 18-months after maintenance therapy randomization to either Sirolimus or Tacrolimus.

Secondary

MeasureTime frameDescription
Number of Participants With Serious Infection (at 6-months After Randomization to Induction Therapy)6-months post-transplantationOccurrence 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).
Number of Participants With Serious Infection (at 18-months After Randomization to Maintenance Therapy)2 years post-transplantationOccurrence of any serious infection (opportunistic or requiring admission to hospital) reported during Period 2 (maintenance therapy randomization to either Sirolimus or Tacrolimus).
Number of Participants With Graft Failure (at 6-months After Randomization to Induction Therapy)6 months post-transplantationReturn to dialysis or re-transplantation by 6-months after randomization to induction therapy.
Number of Participants With Major Vascular Event (at 18-months After Randomization to Maintenance Therapy)2 years post-transplantationComposite of non-fatal myocardial infarction, non-fatal stroke, cardiovascular death or arterial revascularization
Number of Participants With Cancer (at 18-months After Randomization to Maintenance Therapy)2 years post-transplantationOccurrence of any cancer reported during Period 2 (maintenance therapy randomization to either Sirolimus or Tacrolimus).
Number of Participants With Graft Failure (at 18-Months After Randomization to Maintenance Therapy)2 years post-transplantationReturn to dialysis or re-transplantation by 18-months after randomization to maintenance therapy.

Countries

United Kingdom

Participant flow

Recruitment details

3C was conducted in 18 transplant centres in the UK. Recruitment took place between October 2010 and July 2013.

Pre-assignment details

852 participants were randomized for a comparison of Alemtuzumab (426) and Basiliximab (426) based induction therapies. After 6-months, 394 of those participants were re-randomized to either Sirolimus (197) or Tacrolimus (197) based maintenance therapies.

Participants by arm

ArmCount
Period 1: Alemtuzumab/Tacrolimus
Induction therapy allocation: Alemtuzumab (Campath-1H) and Tacrolimus Alemtuzumab: Alemtuzumab 30 mg intravenously or subcutaneously, two doses 24 hours apart. Tacrolimus: Target trough level 5-7 ng/mL for 6-months after alemtuzumab.
426
Period 1: Basiliximab/Tacrolimus
Induction therapy allocation: Basiliximab and Tacrolimus Basiliximab: 20 mg intravenously, two doses 96 hours apart. Tacrolimus: Target trough level 5-12 ng/mL for 6-months after basiliximab.
426
Period 2: Sirolimus
Sirolimus maintenance therapy: target trough level of 6-12 ng/mL for the first 6-months, then reducing to 5-10 ng/mL.
197
Period 2: Tacrolimus
Tacrolimus maintenance therapy: target trough level of 5-7 ng/mL.
197
Total1,246

Withdrawals & dropouts

PeriodReasonFG000FG001FG002FG003
Period 1: Alemtuzumab or BasiliximabNot transplanted141800
Period 1: Alemtuzumab or BasiliximabWithdrawal by Subject0500

Baseline characteristics

CharacteristicPeriod 1: Basiliximab/TacrolimusPeriod 2: TacrolimusPeriod 2: SirolimusTotalPeriod 1: Alemtuzumab/Tacrolimus
Age, Categorical
Age, Period 1
<=18 years
0 Participants0 Participants0 Participants0 Participants0 Participants
Age, Categorical
Age, Period 1
>=65 years
76 Participants0 Participants0 Participants155 Participants79 Participants
Age, Categorical
Age, Period 1
Between 18 and 65 years
350 Participants0 Participants0 Participants697 Participants347 Participants
Age, Categorical
Age, Period 2
<=18 years
0 Participants0 Participants0 Participants0 Participants0 Participants
Age, Categorical
Age, Period 2
>=65 years
0 Participants35 Participants34 Participants69 Participants0 Participants
Age, Categorical
Age, Period 2
Between 18 and 65 years
0 Participants162 Participants163 Participants325 Participants0 Participants
Age, Continuous
Age, Continuous, Period 1
51.8 years
STANDARD_DEVIATION 13.3
——51.9 years
STANDARD_DEVIATION 13.3
52.1 years
STANDARD_DEVIATION 13.3
Age, Continuous
Age, Continuous, Period 2
—52.0 years
STANDARD_DEVIATION 12.9
51.7 years
STANDARD_DEVIATION 13
51.8 years
STANDARD_DEVIATION 13
—
Cold ischaemia time (h)12.9 Hours
STANDARD_DEVIATION 6
——13.4 Hours
STANDARD_DEVIATION 5.9
13.9 Hours
STANDARD_DEVIATION 5.7
Donor sex
Female
179 Participants0 Participants0 Participants372 Participants193 Participants
Donor sex
Male
207 Participants0 Participants0 Participants422 Participants215 Participants
Donor sex
Unknown
40 Participants0 Participants0 Participants58 Participants18 Participants
Highly sensitised
Highly sensitized, Period 1
No
411 Participants0 Participants0 Participants821 Participants410 Participants
Highly sensitised
Highly sensitized, Period 1
Yes
15 Participants0 Participants0 Participants31 Participants16 Participants
Highly sensitised
Highly sensitized, Period 2
No
0 Participants190 Participants193 Participants383 Participants0 Participants
Highly sensitised
Highly sensitized, Period 2
Yes
0 Participants7 Participants4 Participants11 Participants0 Participants
HLA mismatch level
HLA mismatch level, Period 1
Level 1
47 Participants0 Participants0 Participants92 Participants45 Participants
HLA mismatch level
HLA mismatch level, Period 1
Level 2
94 Participants0 Participants0 Participants188 Participants94 Participants
HLA mismatch level
HLA mismatch level, Period 1
Level 3
193 Participants0 Participants0 Participants389 Participants196 Participants
HLA mismatch level
HLA mismatch level, Period 1
Level 4
92 Participants0 Participants0 Participants183 Participants91 Participants
HLA mismatch level
HLA mismatch level, Period 2
Level 1
0 Participants22 Participants23 Participants45 Participants0 Participants
HLA mismatch level
HLA mismatch level, Period 2
Level 2
0 Participants42 Participants42 Participants84 Participants0 Participants
HLA mismatch level
HLA mismatch level, Period 2
Level 3
0 Participants90 Participants89 Participants179 Participants0 Participants
HLA mismatch level
HLA mismatch level, Period 2
Level 4
0 Participants43 Participants43 Participants86 Participants0 Participants
Other Previous Disease
Cancer
5 participants——23 participants18 participants
Other Previous Disease
Diabetes
67 participants——141 participants74 participants
Other Previous Disease
Vascular Disease
49 participants——106 participants57 participants
Previous renal replacement
Haemodialysis
214 Participants0 Participants0 Participants457 Participants243 Participants
Previous renal replacement
None
103 Participants0 Participants0 Participants179 Participants76 Participants
Previous renal replacement
Peritoneal dialysis
106 Participants0 Participants0 Participants210 Participants104 Participants
Previous renal replacement
Transplant
3 Participants0 Participants0 Participants6 Participants3 Participants
Previous transplant
Previous transplant, Period 1
≥1
34 Participants0 Participants0 Participants70 Participants36 Participants
Previous transplant
Previous transplant, Period 1
None
392 Participants0 Participants0 Participants782 Participants390 Participants
Previous transplant
Previous transplant, Period 2
≥1
0 Participants16 Participants16 Participants32 Participants0 Participants
Previous transplant
Previous transplant, Period 2
None
0 Participants181 Participants181 Participants362 Participants0 Participants
Primary Renal Disease
Primary Renal Disease: Period 1
Chronic pyelonephritis
16 Participants0 Participants0 Participants39 Participants23 Participants
Primary Renal Disease
Primary Renal Disease: Period 1
Diabetic kidney disease
49 Participants0 Participants0 Participants100 Participants51 Participants
Primary Renal Disease
Primary Renal Disease: Period 1
Glomerulonephritis
89 Participants0 Participants0 Participants181 Participants92 Participants
Primary Renal Disease
Primary Renal Disease: Period 1
Hypertension
42 Participants0 Participants0 Participants84 Participants42 Participants
Primary Renal Disease
Primary Renal Disease: Period 1
Other
151 Participants0 Participants0 Participants294 Participants143 Participants
Primary Renal Disease
Primary Renal Disease: Period 1
Polycystic kidney disease
73 Participants0 Participants0 Participants141 Participants68 Participants
Primary Renal Disease
Primary Renal Disease: Period 1
Renovascular disease
6 Participants0 Participants0 Participants13 Participants7 Participants
Primary Renal Disease
Primary renal disease, Period 2
Chronic pyelonephritis
0 Participants9 Participants5 Participants14 Participants0 Participants
Primary Renal Disease
Primary renal disease, Period 2
Diabetic kidney disease
0 Participants21 Participants15 Participants36 Participants0 Participants
Primary Renal Disease
Primary renal disease, Period 2
Glomerulonephritis
0 Participants40 Participants50 Participants90 Participants0 Participants
Primary Renal Disease
Primary renal disease, Period 2
Hypertension
0 Participants24 Participants14 Participants38 Participants0 Participants
Primary Renal Disease
Primary renal disease, Period 2
Other
0 Participants65 Participants63 Participants128 Participants0 Participants
Primary Renal Disease
Primary renal disease, Period 2
Polycystic kidney disease
0 Participants34 Participants47 Participants81 Participants0 Participants
Primary Renal Disease
Primary renal disease, Period 2
Renovascular disease
0 Participants4 Participants3 Participants7 Participants0 Participants
Race/Ethnicity, Customized
Ethnic origin, Period 1
Asian
23 Participants0 Participants0 Participants53 Participants30 Participants
Race/Ethnicity, Customized
Ethnic origin, Period 1
Black
21 Participants0 Participants0 Participants42 Participants21 Participants
Race/Ethnicity, Customized
Ethnic origin, Period 1
Other
10 Participants0 Participants0 Participants15 Participants5 Participants
Race/Ethnicity, Customized
Ethnic origin, Period 1
White
372 Participants0 Participants0 Participants742 Participants370 Participants
Race/Ethnicity, Customized
Ethnic origin, Period 2
Asian
0 Participants15 Participants13 Participants28 Participants0 Participants
Race/Ethnicity, Customized
Ethnic origin, Period 2
Black
0 Participants7 Participants5 Participants12 Participants0 Participants
Race/Ethnicity, Customized
Ethnic origin, Period 2
Other
0 Participants2 Participants5 Participants7 Participants0 Participants
Race/Ethnicity, Customized
Ethnic origin, Period 2
White
0 Participants173 Participants174 Participants347 Participants0 Participants
Region of Enrollment
United Kingdom
Period 1: United Kingdom
426 Participants0 Participants0 Participants852 Participants426 Participants
Region of Enrollment
United Kingdom
Period 2: United Kingdom
0 Participants197 Participants197 Participants394 Participants0 Participants
Sex: Female, Male
Sex, Period 1
Female
151 Participants0 Participants0 Participants300 Participants149 Participants
Sex: Female, Male
Sex, Period 1
Male
275 Participants0 Participants0 Participants552 Participants277 Participants
Sex: Female, Male
Sex, Period 2
Female
0 Participants65 Participants65 Participants130 Participants0 Participants
Sex: Female, Male
Sex, Period 2
Male
0 Participants132 Participants132 Participants264 Participants0 Participants
Type of donor
Type of donor, Period 1
Donation after brain death
145 Participants0 Participants0 Participants293 Participants148 Participants
Type of donor
Type of donor, Period 1
Donation after circulatory death
158 Participants0 Participants0 Participants316 Participants158 Participants
Type of donor
Type of donor, Period 1
Donation from living (related or unrelated) person
123 Participants0 Participants0 Participants243 Participants120 Participants
Type of donor
Type of donor, Period 2
Donation after brain death
0 Participants65 Participants66 Participants131 Participants0 Participants
Type of donor
Type of donor, Period 2
Donation after circulatory death
0 Participants69 Participants65 Participants134 Participants0 Participants
Type of donor
Type of donor, Period 2
Donation from living (related or unrelated) person
0 Participants63 Participants66 Participants129 Participants0 Participants
Virology serology
CMV-positive donor to negative recipient
102 Participants——206 Participants104 Participants
Virology serology
EBV-positive donor to negative recipient
19 Participants——40 Participants21 Participants

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
EG002
affected / at risk
EG003
affected / at risk
deaths
Total, all-cause mortality
11 / 4266 / 42611 / 1979 / 197
other
Total, other adverse events
0 / 00 / 00 / 00 / 0
serious
Total, serious adverse events
341 / 426354 / 426140 / 197134 / 197

Outcome results

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.

Time frame: 2 years post-transplantation

ArmMeasureValue (MEAN)Dispersion
Period 1: Alemtuzumab/TacrolimusGraft Function (at 18-months After Randomization to Maintenance Therapy)53.7 mL/min/1.73m²Standard Error 0.9
Period 1: Basiliximab/TacrolimusGraft Function (at 18-months After Randomization to Maintenance Therapy)54.6 mL/min/1.73m²Standard Error 0.9
p-value: 0.5ANCOVA
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))

Time frame: 6 months post-transplantation

ArmMeasureValue (COUNT_OF_PARTICIPANTS)
Period 1: Alemtuzumab/TacrolimusNumber of Participants With Biopsy-proven Acute Rejection at 6-months After Randomization to Induction Therapy31 Participants
Period 1: Basiliximab/TacrolimusNumber of Participants With Biopsy-proven Acute Rejection at 6-months After Randomization to Induction Therapy68 Participants
p-value: <0.000195% CI: [0.28, 0.64]Log Rank
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).

Time frame: 2 years post-transplantation

ArmMeasureValue (COUNT_OF_PARTICIPANTS)
Period 1: Alemtuzumab/TacrolimusNumber of Participants With Cancer (at 18-months After Randomization to Maintenance Therapy)17 Participants
Period 1: Basiliximab/TacrolimusNumber of Participants With Cancer (at 18-months After Randomization to Maintenance Therapy)17 Participants
p-value: 0.9995% CI: [0.51, 1.97]Log Rank
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.

Time frame: 2 years post-transplantation

ArmMeasureValue (COUNT_OF_PARTICIPANTS)
Period 1: Alemtuzumab/TacrolimusNumber of Participants With Graft Failure (at 18-Months After Randomization to Maintenance Therapy)8 Participants
Period 1: Basiliximab/TacrolimusNumber of Participants With Graft Failure (at 18-Months After Randomization to Maintenance Therapy)4 Participants
p-value: 0.2395% CI: [0.64, 6.18]Log Rank
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.

Time frame: 6 months post-transplantation

ArmMeasureValue (COUNT_OF_PARTICIPANTS)
Period 1: Alemtuzumab/TacrolimusNumber of Participants With Graft Failure (at 6-months After Randomization to Induction Therapy)16 Participants
Period 1: Basiliximab/TacrolimusNumber of Participants With Graft Failure (at 6-months After Randomization to Induction Therapy)13 Participants
p-value: 0.5895% CI: [0.59, 2.55]Regression, Cox
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

Time frame: 2 years post-transplantation

ArmMeasureValue (COUNT_OF_PARTICIPANTS)
Period 1: Alemtuzumab/TacrolimusNumber of Participants With Major Vascular Event (at 18-months After Randomization to Maintenance Therapy)10 Participants
Period 1: Basiliximab/TacrolimusNumber of Participants With Major Vascular Event (at 18-months After Randomization to Maintenance Therapy)13 Participants
p-value: 0.5295% CI: [0.34, 1.73]Log Rank
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).

Time frame: 2 years post-transplantation

ArmMeasureValue (COUNT_OF_PARTICIPANTS)
Period 1: Alemtuzumab/TacrolimusNumber of Participants With Serious Infection (at 18-months After Randomization to Maintenance Therapy)95 Participants
Period 1: Basiliximab/TacrolimusNumber of Participants With Serious Infection (at 18-months After Randomization to Maintenance Therapy)70 Participants
p-value: 0.00895% CI: [1.11, 2.06]Log Rank
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).

Time frame: 6-months post-transplantation

ArmMeasureValue (COUNT_OF_PARTICIPANTS)
Period 1: Alemtuzumab/TacrolimusNumber of Participants With Serious Infection (at 6-months After Randomization to Induction Therapy)135 Participants
Period 1: Basiliximab/TacrolimusNumber of Participants With Serious Infection (at 6-months After Randomization to Induction Therapy)136 Participants
p-value: 0.8895% CI: [0.8, 1.29]Regression, Cox

Source: ClinicalTrials.gov · Data processed: Mar 23, 2026