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

NCT00240994 | Completed Phase 2 Results DMC

• 1 other identifier: DAIT PC01
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 4

Brief Summary

The purpose of this study is to evaluate the safety of alemtuzumab after kidney transplantation as part of a multitherapy regimen to prevent kidney graft loss and death and to avoid steroids and chronic use of calcineurin inhibitors in pediatric renal transplant recipients 1 to 20 years of age.

Conditions

Kidney Failure, Chronic; Kidney Transplantation; Immunosuppression

Keywords

End stage renal disease; Kidney transplantation; Renal transplantation; Kidney failure; Pediatric renal transplant recipients; Alemtuzumab; Campath; Mycophenolate mofetil; MMF; CellCept; Tacrolimus; Prograf; Sirolimus; Rapamycin

Outcome Measures

Primary Outcomes (1)

• The Proportion of Participants With Graft Loss or Death Within 12 Months Post Kidney Transplantation

  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.

  Up to one year post kidney transplantation procedure

Study Arms (1)

Alemtuzumab (Campath)

EXPERIMENTAL

In this open-label, single-arm trial , participants will be administered a 0.3 mg/kg dose of alemtuzumab (Campath) intravenously one day prior to kidney transplantation and one day post kidney transplantation. Participants will then receive 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.

Drug: Alemtuzumab; Drug: Tacrolimus; Drug: Mycophenolate mofetil; Drug: Sirolimus

Interventions

Alemtuzumab DRUG

Administered intravenously over a period of 2-3 hours. Two doses total, the first will be one day before transplant and the second will be on the day following transplantation. Pre-medication with methylprednisolone, acetaminophen, and Benadryl will be administered before each dose.

Also known as: Campath, Campath- 1H

Alemtuzumab (Campath)

Tacrolimus DRUG

Administered orally at a dose of 0.05-0.1 mg/kg twice daily, beginning 1-3 days following transplantation and continuing until weeks 8-12. Tacrolimus will be discontinued and a treatment regimen with sirolimus will be initiated between weeks 8-12 but some overlap with these medications is possible.

Also known as: Prograf

Alemtuzumab (Campath)

Mycophenolate mofetil DRUG

Per recommendation

Also known as: CellCept

Alemtuzumab (Campath)

Sirolimus DRUG

Administered by either liquid or tablet every 12 hours from month 6 until month 24. Dosage will vary throughout the treatment course.

Also known as: Rapamycin

Alemtuzumab (Campath)

Eligibility Criteria

• Age: 1 Year - 20 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Between the ages of 1 to 20 (prior to 21st birthday)
• End Stage Renal Disease
• Necessity of kidney transplant
• First kidney transplant received from a living donor
• A living kidney donor identified
• No known contraindications to therapy with alemtuzumab
• Negative pregnancy test before study entry
• Willing to use approved methods of contraception for the duration of the study, 6 weeks after discontinuation of MMF, and 12 weeks after discontinuation of sirolimus
• Informed consent from participant, parent, or guardian
• Current vaccinations, including varicella-zoster (VZV) vaccine, before study enrollment

You may not qualify if:

• Recipient of a deceased donor kidney transplant
• Multiorgan transplant
• History of prior organ transplantation
• Participant sensitized to greater than 0% Panel Reactive Antibody (PRA) within 4 weeks before study enrollment. (If participant receives a blood transfusion status post PRA test, then the PRA must be repeated within 1 week of transplantation)
• Participants with human leukocyte antigen (HLA) identical living related donors
• History of primary focal segmented glomerulosclerosis
• History of other disorders requiring continuous maintenance steroids or calcineurin inhibitors
• Active systemic infection at time of transplant
• History of malignancy
• Infected with human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV)
• Contraindication to receive tacrolimus, sirolimus, MMF, or monoclonal antibody therapy
• Use of investigational drugs within 4 weeks before study enrollment
• Recipient of any licensed or investigational live attenuated vaccine(s) within 2 months before study enrollment
• Family history of high cholesterol

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead
• Cooperative Clinical Trials in Pediatric Transplantation: collaborator

Study Sites (4)

University of California, San Francisco

San Francisco, California, 94143-0116, United States

Location

Children's Hospital, Boston

Boston, Massachusetts, 02115, United States

Location

Children's Hospital, Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Children's Hospital and Regional Medical Center, Seattle

Seattle, Washington, 98105, United States

Location

Related Publications (6)

• 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. doi: 10.1007/s004670050531.

  PMID: 9874312 BACKGROUND

• 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. doi: 10.1097/01.tp.0000128625.29654.eb.

  PMID: 15316372 BACKGROUND

• Rao V, Pirsch JD, Becker BN, Knechtle SJ. Sirolimus monotherapy following Campath-1H induction. Transplant Proc. 2003 May;35(3 Suppl):128S-130S. doi: 10.1016/s0041-1345(03)00227-6.

  PMID: 12742484 BACKGROUND

• Kreis H, Cisterne JM, Land W, Wramner L, Squifflet JP, Abramowicz D, Campistol JM, Morales JM, Grinyo JM, Mourad G, Berthoux FC, Brattstrom 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. doi: 10.1097/00007890-200004150-00009.

  PMID: 10798738 BACKGROUND

• 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. doi: 10.1111/j.1600-6143.2005.00822.x.

  PMID: 15888040 BACKGROUND

• 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.

  PMID: 22052056 RESULT

Related Links

• National Institute of Allergy and Infectious Diseases (NIAID)
• Division of Allergy, Immunology, and Transplantation (DAIT)

MeSH Terms

Conditions

Kidney Failure, Chronic; Renal Insufficiency

Interventions

Alemtuzumab; Tacrolimus; Mycophenolic Acid; Sirolimus

Condition Hierarchy (Ancestors)

Renal Insufficiency, Chronic; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Macrolides; Lactones; Organic Chemicals; Caproates; Acids, Acyclic; Carboxylic Acids; Fatty Acids; Lipids

Results Point of Contact

• Title: Associate Director, Clinical Research Program
• Organization: DAIT/NIAID

DAITClinicalTrialsGov@niaid.nih.gov

301-594-7669

Study Officials

• William Harmon, MD

  Boston Children's Hospital

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 14, 2005
• First Posted: October 18, 2005
• Study Start: January 1, 2005
• Primary Completion: November 1, 2009
• Study Completion: November 1, 2009
• Last Updated: January 2, 2017
• Results First Posted: October 25, 2012

Record last verified: 2016-11

Data Sharing

• IPD Sharing: Will share

Locations

US (4)