Primary Outcome Measures:
- Proportion of participants who have graft loss or death [ Time Frame: At 12 month post transpla nt ] [ Designated as safety issue: Yes ]
Secondary Outcome Measures:
- Longer term patient and graft survival [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
- Occurrence, severity, and treatment for acute and humoral rejection [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
- Incidence of chronic allograft nephropathy [ Time Frame: At Months 6 and 24 ] [ Designated as safety issue: No ]
- Change in serum creatinine [ Time Frame: At Day 3, andMonths 6 and 12 post transplant ] [ Designated as safety issue: No ]
- kidney function [ Time Frame: At Month 12 ] [ Designated as safety issue: No ]
- Incidence and severity of hyperlipidemia, hypertension, anemia, leukopenia, neutropenia, and the requirement for treatment [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
- Infectious complications, including bacterial, viral, and fungal infections [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
- Surgical complications [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
- Incidence and duration of re-hospitalizations after transplantation [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
- Incidence of biopsy proven post-transplant lymphoproliferative disorder (PTLD) [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
- Incidence of opportunistic infections, especially cytomegalovirus (CMV) and Epstein-Barr virus (EBV) viremia [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
- Treatment for viremia and disease [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
- Incidence of delayed graft function [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
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 aged 1 to 10 years of age. However, young children now have more infections following transplant previously. Also, improved graft survival is not observed in adolescents aged 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 children and adolescents.
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. All participants will receive intravenous (IV) alemtuzumab one day before transplantation and 1 day after transplantation. Mycophenolate mofetil (MMF) will be administered orally no later than 2 days after transplantation. Participants will begin to take oral tacrolimus twice a day 1 to 3 days after transplantation until Weeks 8 through 12 when sirolimus will be initiated. 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 renal biopsies will be performed at transplant, during Weeks 8 through 12 immediately before conversion to sirolimus, and at Months 6 and 24.
Purpose
