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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Kidney Failure, Chronic, Kidney Transplantation, Immunosuppression

Intervention / Treatment
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* Drug: Alemtuzumab
* Drug: Tacrolimus
* Drug: Mycophenolate mofetil
* Drug: Sirolimus


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 1 Year
Maximum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Alemtuzumab (Campath)<br>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<br>* 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.<br>* Other names: Campath- 1H;Drug: Tacrolimus<br>* 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.<br>* Other names: Prograf;Drug: Mycophenolate mofetil<br>* Per recommendation<br>* Other names: CellCept;Drug: Sirolimus<br>* Administered by either liquid or tablet every 12 hours from month 6 until month 24. Dosage will vary throughout the treatment course.<br>* Other names: Rapamycin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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End stage renal disease, Kidney transplantation, Renal transplantation, Kidney failure, Pediatric renal transplant recipients, Alemtuzumab, Campath, Mycophenolate mofetil, MMF, CellCept, Tacrolimus, Prograf, Sirolimus, Rapamycin