Clinical trial NCT00240994: Safety in Immunomodulatory Functions of Alemtuzumab (Campath) in Pediatric Kidney Transplantation Recipients
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
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
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
Collaborators: name: Cooperative Clinical Trials in Pediatric Transplantation
First posted: 2005-10-18
Enrollment: 35
Sex: ALL
Minimum age (years): 1
Maximum age (years): 20
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: The Proportion of Participants With Graft Loss or Death Within 12 Months Post Kidney Transplantation
timeFrame: Up to one year post kidney transplantation procedure
Secondary outcomes:
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
city: Boston
country: United States
facility: Children's Hospital, Boston
state: Massachusetts
city: Philadelphia
country: United States
facility: Children's Hospital, Philadelphia
state: Pennsylvania
city: Seattle
country: United States
facility: Children's Hospital and Regional Medical Center, Seattle
state: Washington
Study officials:
affiliation: Boston Children's Hospital
name: William Harmon, MD
role: STUDY_CHAIR
References:
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. doi: 10.1007/s004670050531.
citation: 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.
citation: 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.
citation: 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.
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. doi: 10.1111/j.1600-6143.2005.00822.x.
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 2011 Nov 3.