Safety in Immunomodulatory Functions of Alemtuzumab (Campath) in Pediatric Kidney Transplantation Recipients

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ClinicalTrials.gov Identifier: NCT00240994

Recruitment Status : Completed

First Posted : October 18, 2005

Results First Posted : October 25, 2012

Last Update Posted : January 2, 2017

Sponsor:

Collaborator:

Cooperative Clinical Trials in Pediatric Transplantation

Information provided by (Responsible Party):

National Institute of Allergy and Infectious Diseases (NIAID)

Study Type	Interventional
Study Design	Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Prevention
Conditions	Kidney Failure, Chronic Kidney Transplantation Immunosuppression
Interventions	Drug: Alemtuzumab Drug: Tacrolimus Drug: Mycophenolate mofetil Drug: Sirolimus
Enrollment	35

Participant Flow

Recruitment Details	Four centers in the United States recruited 35 subjects between January 2005 and October 2007 who were less than 21 years of age and first time living-donor kidney allograft recipients.
Pre-assignment Details	At a screening visit, participants underwent procedures to establish inclusion/exclusion criteria and then sign the informed consent form.


Arm/Group Title	Alemtuzumab (Campath)
Arm/Group Description	In this open-label, single-arm tria...
Arm/Group Description	In this open-label, single-arm trial, participants were administered a 0.3 mg/kg dose of alemtuzumab intravenously one day prior to kidney transplantation and one day post kidney transplantation. Participants were then administered a maintenance immunosuppressive regimen of tacrolimus and mycophenolate mofetil (MMF) for 8 to 12 weeks, followed by sirolimus and MMF until 24 months post transplantation.
Period Title: Overall Study
Started	35
Completed	32
Not Completed	3
Reason Not Completed
Lost to Follow-up	1
Protocol Violation	1
Graft failure	1

Baseline Characteristics

Arm/Group Title		Alemtuzumab (Campath)
Arm/Group Description		In this open-label, single-arm tria...
Arm/Group Description		In this open-label, single-arm trial, participants were administered a 0.3 mg/kg dose of alemtuzumab intravenously one day prior to kidney transplantation and one day post kidney transplantation. Participants were then administered a maintenance immunosuppressive regimen of tacrolimus and mycophenolate mofetil (MMF) for 8 to 12 weeks, followed by sirolimus and MMF until 24 months post transplantation.
Overall Number of Baseline Participants		35
Baseline Analysis Population Description		[Not Specified]
Baseline Analysis Population Description		[Not Specified]
Age, Continuous Mean (Standard Deviation) Unit of measure: Years	Number Analyzed	35 participants
Final status: Completed (N=22)		13.1 (5.0)
Final status: Discontinued Therapy (N=10)		9.8 (6.2)
Final status: Discontinued Study (N=3)		17.7 (2.4)
All Participants (N=35)		12.6 (5.5)
Gender Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	35 participants
	Female	20 57.1%
	Male	15 42.9%
Region of Enrollment Measure Type: Number Unit of measure: Participants
United States	Number Analyzed	35 participants
United States		35

Outcome Measures

1.Primary Outcome


Title	The Proportion of Participants With Graft Loss or Death Within 12 Months Post Kidney Transplantation
Description	Graft loss is defined as the need for dialysis for more than 30 days d...
Description	Graft loss is defined as the need for dialysis for more than 30 days duration, allograft nephrectomy, or the decision to withdraw immunosuppression due to graft failure.
Time Frame	Up to one year post kidney transplantation procedure

Outcome Measure Data

Analysis Population Description

Intent-to-treat


Arm/Group Title	Alemtuzumab (Campath)
Arm/Group Description:	In this open-label, single-arm tria...
Arm/Group Description:	In this open-label, single-arm trial, participants were administered a 0.3 mg/kg dose of alemtuzumab intravenously one day prior to kidney transplantation and one day post kidney transplantation. Participants were then administered a maintenance immunosuppressive regimen of tacrolimus and mycophenolate mofetil (MMF) for 8 to 12 weeks, followed by sirolimus and MMF until 24 months post transplantation.
Overall Number of Participants Analyzed	35
Measure Type: Number Unit of Measure: Proportion of participants
	0.057

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Alemtuzumab (Campath)
	Comments	The proportion of participants with graft loss or death within 12 months post kidney transplantation is descriptively summarized with a 95% confidence interval using an exact binomial method.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	[Not Specified]
	Comments	[Not Specified]
	Method	95% Confidence Interval
	Comments	95% CI using an exact binomial method

Method of Estimation	Estimation Parameter	Proportion with graft loss or death
	Estimated Value	.057
	Confidence Interval	(2-Sided) 95% 0.007 to 0.192
	Estimation Comments	[Not Specified]

Adverse Events

Time Frame	From beginning of study to end of study
Adverse Event Reporting Description	This study graded the severity of adverse events experienced by the study participants according to criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003)

Arm/Group Title	Alemtuzumab (Campath)
Arm/Group Description	In this open-label, single-arm tria...
Arm/Group Description	In this open-label, single-arm trial , participants were administered a 0.3 mg/kg dose of alemtuzumab intravenously one day prior to kidney transplantation and one day post kidney transplantation. Participants were then administered a maintenance immunosuppressive regimen of tacrolimus and mycophenolate mofetil (MMF) for 8 to 12 weeks, followed by sirolimus and MMF until 24 months post transplantation.
All-Cause Mortality
	Alemtuzumab (Campath)
	Affected / at Risk (%)
Total	--/--
Serious Adverse Events Serious Adverse Events
	Alemtuzumab (Campath)
	Affected / at Risk (%)	# Events
Total	25/35 (71.43%)
Blood and lymphatic system disorders
Anaemia ^† 1	1/35 (2.86%)	1
Leukopenia ^† 1	1/35 (2.86%)	1
Neutropenia ^† 1	4/35 (11.43%)	4
Thrombotic microangiopathy ^† 1	1/35 (2.86%)	1
Gastrointestinal disorders
Abdominal compartment syndrome ^† 1	1/35 (2.86%)	1
Abdominal pain ^† 1	1/35 (2.86%)	1
Ascites ^† 1	1/35 (2.86%)	2
Diarrhoea ^† 1	4/35 (11.43%)	4
Mouth ulceration ^† 1	1/35 (2.86%)	1
General disorders
Adverse drug reaction ^† 1	1/35 (2.86%)	1
Oedema ^† 1	1/35 (2.86%)	1
Pyrexia ^† 1	5/35 (14.29%)	5
Immune system disorders
Graft loss ^† 1	2/35 (5.71%)	2
Hypersensitivity ^† 1	1/35 (2.86%)	1
Kidney transplant rejection ^† 1	2/35 (5.71%)	2
Transplant rejection ^† 1	3/35 (8.57%)	4
Infections and infestations
Adenovirus infection ^† 1	1/35 (2.86%)	1
Arthritis bacterial ^† 1	1/35 (2.86%)	1
Bacterial pyelonephritis ^† 1	1/35 (2.86%)	1
Catheter site cellulitis ^† 1	1/35 (2.86%)	1
Cellulitis ^† 1	1/35 (2.86%)	1
Central line infection ^† 1	1/35 (2.86%)	1
Gastroenteritis ^† 1	3/35 (8.57%)	4
Herpes simplex ^† 1	1/35 (2.86%)	2
Influenza ^† 1	1/35 (2.86%)	1
Klebsiella infection ^† 1	1/35 (2.86%)	1
Lobar pneumonia ^† 1	1/35 (2.86%)	1
Pneumonia ^† 1	2/35 (5.71%)	2
Pyelonephritis ^† 1	2/35 (5.71%)	3
Rhinovirus infection ^† 1	1/35 (2.86%)	1
Urinary tract infection ^† 1	1/35 (2.86%)	2
Injury, poisoning and procedural complications
Arteriovenous fistula occlusion ^† 1	1/35 (2.86%)	1
Arteriovenous fistula thrombosis ^† 1	1/35 (2.86%)	1
Post procedural haemorrhage ^† 1	1/35 (2.86%)	1
Investigations
Blood creatinine increased ^† 1	4/35 (11.43%)	6
Blood culture positive ^† 1	1/35 (2.86%)	1
Metabolism and nutrition disorders
Dehydration ^† 1	2/35 (5.71%)	2
Hypervolaemia ^† 1	1/35 (2.86%)	1
Musculoskeletal and connective tissue disorders
Epiphyseal disorder ^† 1	1/35 (2.86%)	1
Tenosynovitis ^† 1	1/35 (2.86%)	1
Nervous system disorders
Grand mal convulsion ^† 1	1/35 (2.86%)	1
Psychiatric disorders
Depressed mood ^† 1	1/35 (2.86%)	1
Renal and urinary disorders
Anuria ^† 1	1/35 (2.86%)	1
Glomerulonephritis focal ^† 1	1/35 (2.86%)	1
Pelvi-ureteric obstruction ^† 1	1/35 (2.86%)	1
Proteinuria ^† 1	1/35 (2.86%)	1
Renal failure ^† 1	1/35 (2.86%)	1
Urinoma ^† 1	1/35 (2.86%)	1
Reproductive system and breast disorders
Epididymitis ^† 1	1/35 (2.86%)	1
Respiratory, thoracic and mediastinal disorders
Asthma ^† 1	1/35 (2.86%)	2
Pneumothorax ^† 1	1/35 (2.86%)	1
Respiratory distress ^† 1	1/35 (2.86%)	1
Skin and subcutaneous tissue disorders
Skin disorder ^† 1	1/35 (2.86%)	2
Skin lesion ^† 1	1/35 (2.86%)	1
Urticaria ^† 1	1/35 (2.86%)	1
Surgical and medical procedures
Gastrostomy closure ^† 1	1/35 (2.86%)	1
Suture removal ^† 1	1/35 (2.86%)	1
Vascular disorders
Hypotension ^† 1	1/35 (2.86%)	1
† Indicates events were collected by systematic assessment 1 Term from vocabulary, MedDRA 11.1
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Alemtuzumab (Campath)
	Affected / at Risk (%)	# Events
Total	34/35 (97.14%)
Blood and lymphatic system disorders
Anaemia ^† 1	20/35 (57.14%)	35
Leukopenia ^† 1	23/35 (65.71%)	70
Lymphopenia ^† 1	4/35 (11.43%)	6
Neutropenia ^† 1	14/35 (40.00%)	26
Gastrointestinal disorders
Abdominal pain ^† 1	4/35 (11.43%)	4
Anal ulcer ^† 1	2/35 (5.71%)	3
Diarrhoea ^† 1	12/35 (34.29%)	15
Mouth ulceration ^† 1	5/35 (14.29%)	11
Nausea ^† 1	3/35 (8.57%)	4
Stomatitis ^† 1	2/35 (5.71%)	2
Vomiting ^† 1	3/35 (8.57%)	3
General disorders
Fatigue ^† 1	2/35 (5.71%)	2
Infusion related reaction ^† 1	4/35 (11.43%)	4
Oedema peripheral ^† 1	3/35 (8.57%)	4
Pain ^† 1	2/35 (5.71%)	2
Pyrexia ^† 1	7/35 (20.00%)	9
Immune system disorders
Cytokine release syndrome ^† 1	3/35 (8.57%)	3
Transplant rejection ^† 1	2/35 (5.71%)	3
Infections and infestations
Bronchitis ^† 1	2/35 (5.71%)	2
Bronchitis acute ^† 1	2/35 (5.71%)	2
Cellulitis ^† 1	2/35 (5.71%)	2
Chronic sinusitis ^† 1	2/35 (5.71%)	2
Cystitis klebsiella ^† 1	4/35 (11.43%)	8
Ear infection ^† 1	2/35 (5.71%)	3
Gastroenteritis ^† 1	2/35 (5.71%)	2
Impetigo ^† 1	2/35 (5.71%)	2
Nasopharyngitis ^† 1	2/35 (5.71%)	2
Otitis media ^† 1	2/35 (5.71%)	2
Sinusitis ^† 1	7/35 (20.00%)	10
Upper respiratory tract infection ^† 1	3/35 (8.57%)	3
Urinary tract infection ^† 1	5/35 (14.29%)	8
Urinary tract infection enterococcal ^† 1	3/35 (8.57%)	6
Viraemia ^† 1	3/35 (8.57%)	4
Injury, poisoning and procedural complications
Anaemia postoperative ^† 1	2/35 (5.71%)	2
Post procedural pain ^† 1	2/35 (5.71%)	2
Investigations
Blood cholesterol increased ^† 1	2/35 (5.71%)	2
Blood creatine phosphokinase increased ^† 1	3/35 (8.57%)	3
Blood creatinine increased ^† 1	5/35 (14.29%)	7
Blood parathyroid hormone increased ^† 1	3/35 (8.57%)	3
Blood pressure increased ^† 1	2/35 (5.71%)	2
Epstein-Barr virus antibody positive ^† 1	3/35 (8.57%)	3
Haematocrit decreased ^† 1	2/35 (5.71%)	2
Haemoglobin decreased ^† 1	5/35 (14.29%)	9
Neutrophil count decreased ^† 1	2/35 (5.71%)	3
Transferrin saturation decreased ^† 1	2/35 (5.71%)	2
Weight increased ^† 1	3/35 (8.57%)	3
Metabolism and nutrition disorders
Dehydration ^† 1	3/35 (8.57%)	3
Food intolerance ^† 1	2/35 (5.71%)	2
Hypercalcaemia ^† 1	3/35 (8.57%)	3
Hypercholesterolaemia ^† 1	2/35 (5.71%)	2
Hyperglycaemia ^† 1	4/35 (11.43%)	5
Hyperkalaemia ^† 1	6/35 (17.14%)	7
Hyperlipidaemia ^† 1	8/35 (22.86%)	8
Hypertriglyceridaemia ^† 1	3/35 (8.57%)	3
Hypoalbuminaemia ^† 1	6/35 (17.14%)	7
Hypocalcaemia ^† 1	3/35 (8.57%)	3
Hypokalaemia ^† 1	5/35 (14.29%)	8
Hypomagnesaemia ^† 1	3/35 (8.57%)	3
Hypophosphataemia ^† 1	9/35 (25.71%)	11
Musculoskeletal and connective tissue disorders
Arthralgia ^† 1	2/35 (5.71%)	2
Pain in extremity ^† 1	3/35 (8.57%)	4
Nervous system disorders
Headache ^† 1	2/35 (5.71%)	2
Migraine ^† 1	2/35 (5.71%)	2
Psychiatric disorders
Anxiety ^† 1	3/35 (8.57%)	4
Depression ^† 1	3/35 (8.57%)	3
Insomnia ^† 1	2/35 (5.71%)	2
Panic attack ^† 1	2/35 (5.71%)	2
Renal and urinary disorders
Haematuria ^† 1	4/35 (11.43%)	4
Hydronephrosis ^† 1	3/35 (8.57%)	3
Hypercalciuria ^† 1	2/35 (5.71%)	2
Proteinuria ^† 1	5/35 (14.29%)	7
Respiratory, thoracic and mediastinal disorders
Pharyngolaryngeal pain ^† 1	4/35 (11.43%)	5
Skin and subcutaneous tissue disorders
Pruritus ^† 1	2/35 (5.71%)	2
Rash ^† 1	2/35 (5.71%)	3
Vascular disorders
Hypertension ^† 1	16/35 (45.71%)	18
† Indicates events were collected by systematic assessment 1 Term from vocabulary, MedDRA 11.1

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT 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.

Results Point of Contact

Layout table for Results Point of Contact information

Name/Title:	Associate Director, Clinical Research Program
Organization:	DAIT/NIAID
Phone:	301-594-7669
EMail:	DAITClinicalTrialsGov@niaid.nih.gov

Publications of Results:

De Serres SA, Mfarrej BG, Magee CN, Benitez F, Ashoor I, Sayegh MH, Harmon WE, Najafian N. Immune profile of pediatric renal transplant recipients following alemtuzumab induction. J Am Soc Nephrol. 2012 Jan;23(1):174-82. doi: 10.1681/ASN.2011040360. Epub 2011 Nov 3.

Other Publications:

Wolff G, Strecker K, Vester U, Latta K, Ehrich JH. Non-compliance following renal transplantation in children and adolescents. Pediatr Nephrol. 1998 Nov;12(9):703-8. Review.

Ciancio G, Burke GW, Gaynor JJ, Mattiazzi A, Roohipour R, Carreno MR, Roth D, Ruiz P, Kupin W, Rosen A, Esquenazi V, Tzakis AG, Miller J. The use of Campath-1H as induction therapy in renal transplantation: preliminary results. Transplantation. 2004 Aug 15;78(3):426-33.

Rao V, Pirsch JD, Becker BN, Knechtle SJ. Sirolimus monotherapy following Campath-1H induction. Transplant Proc. 2003 May;35(3 Suppl):128S-130S.

Kreis H, Cisterne JM, Land W, Wramner L, Squifflet JP, Abramowicz D, Campistol JM, Morales JM, Grinyo JM, Mourad G, Berthoux FC, Brattström C, Lebranchu Y, Vialtel P. Sirolimus in association with mycophenolate mofetil induction for the prevention of acute graft rejection in renal allograft recipients. Transplantation. 2000 Apr 15;69(7):1252-60.

Watson CJ, Bradley JA, Friend PJ, Firth J, Taylor CJ, Bradley JR, Smith KG, Thiru S, Jamieson NV, Hale G, Waldmann H, Calne R. Alemtuzumab (CAMPATH 1H) induction therapy in cadaveric kidney transplantation--efficacy and safety at five years. Am J Transplant. 2005 Jun;5(6):1347-53.

Layout table for additonal information

Responsible Party:	National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:	NCT00240994
Other Study ID Numbers:	DAIT PC01
First Submitted:	October 14, 2005
First Posted:	October 18, 2005
Results First Submitted:	September 13, 2012
Results First Posted:	October 25, 2012
Last Update Posted:	January 2, 2017

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