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

Kidney Transplantation Clinical Trial

Official title:

A Phase II Exploratory Study to Determine the Safety and Study the Immunomodulatory Functions of Induction Therapy With Campath, Combined With Chronic Immunosuppression With Mycophenolate Mofetil and Sirolimus

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00240994
• Other study ID #: DAIT PC01
• Status: Completed
• Phase: Phase 2
• First received: October 14, 2005
• Last updated: October 25, 2012
• Start date: January 2005
• Est. completion date: November 2009

Study information

• Verified date: September 2012
• Source: National Institute of Allergy and Infectious Diseases (NIAID)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

Description:

Kidney transplantation is widely considered to be the treatment of choice for children with End Stage Renal Disease (ESRD). Improvements in surgical techniques, donor selection, and immunosuppression practices, as well as the enhanced experience of specialized pediatric transplant teams, have all led to marked improvements in patient and kidney graft survival in infants and young children ages 1 to 10. However, young children now have more infections following transplant previously. Also, improved graft survival is not observed in pediatric renal transplant recipients 11 to 17 years of age. Some studies do indicate that the poor long term outcome of patient and kidney survival observed in this age group may be caused by noncompliance with immunosuppressive medications. Therefore, protocols that minimize the use of immunosuppressive medications while retaining kidney function are necessary for improving graft and patient survival in children. This study will evaluate the safety of a regimen containing alemtuzumab after kidney transplantation, followed by steroid avoidance and calcineurin inhibitor withdrawal in pediatric renal transplant recipients 1 to 20 years of age.

The accrual period is scheduled for 18 months. The study follow-up period will last 24 months. All participants enrolled will undergo this treatment schedule: 1.) All participants will receive intravenous alemtuzumab one day before transplantation and 1 day after transplantation. 2.) Mycophenolate mofetil (MMF) will be administered orally no later than 2 days after transplantation. 3.) Participants will begin to take oral tacrolimus twice a day 1 to 3 days after transplantation until Weeks 8 through 12 when 4.) Sirolimus will be initiated. 5.) Sirolimus and MMF will be taken orally until Month 24.

Blood collection will occur at baseline, 1 day before transplant, at Days 1 and 3, at Weeks 2, 4, 6, 8, 10, and at Months 3 through 24. Scheduled kidney (renal) biopsies will be performed at transplant, during Weeks 8 through 12, immediately before conversion to sirolimus, and at Months 6 and 24.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 35
• Est. completion date: November 2009
• Est. primary completion date: November 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 1 Year to 20 Years

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

Study Design

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Immunosuppression
• Kidney Failure, Chronic
• Kidney Transplantation
• Renal Insufficiency

Intervention

Drug:
• Alemtuzumab
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.
• Tacrolimus
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. Tacromlimus will be discontinued and a treatment regimen with sirolimus will be initiated between weeks 8-12 but some overlap with these medications is possible.
• Mycophenolate mofetil
Per recommendation
• Sirolimus
Administered by either liquid or tablet every 12 hours from month 6 until month 24. Dosage will vary throughout the treatment course.

Locations

Country	Name	City	State
United States	Children's Hospital, Boston	Boston	Massachusetts
United States	Children's Hospital, Philadelphia	Philadelphia	Pennsylvania
United States	University of California, San Francisco	San Francisco	California
United States	Children's Hospital and Regional Medical Center, Seattle	Seattle	Washington

Sponsors (2)

Lead Sponsor	Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)	Cooperative Clinical Trials in Pediatric Transplantation

Country where clinical trial is conducted

United States, 

References & Publications (6)

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. — View Citation

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 — View Citation

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. — View Citation

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

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Yes