Clinical trial NCT00768729: Safety of Immunosuppression Minimization in Children and Adolescents After Kidney Transplantation
Official title: Immunosuppression Minimization to Single Drug Therapy With Sirolimus (Rapamune) in Pediatric Transplantation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Kidney Failure, Chronic
Kidney Transplantation
Immunosuppression
Keywords: End stage renal disease
Kidney transplantation
Renal transplantation
Kidney failure
Children
Adolescents
Sirolimus
Rapamycin
CellCept
Mycophenolate mofetil (MMF)
Azathioprine
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
First posted: 2008-10-08
Enrollment: 7
Sex: ALL
Minimum age (years): 1
Maximum age (years): 20
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

Brief summary: Kidney transplantation is widely considered to be the treatment of choice for children with End Stage Renal Disease (ESRD). The purpose of this study is to determine the safety of sirolimus monotherapy for long-term immunosuppression in children and adolescents after kidney transplantation.

Detailed description: Improvements in surgical techniques, donor selection, immunosuppression practices, and 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 Long-term graft survival rates decrease in adolescents 11 to 17 years of age. Several studies have suggested this decrease may be the result of noncompliance with immunosuppressive medications in this age group. Therefore, protocols that minimize the use of immunosuppressive medications, while retaining kidney function are necessary for improving graft and patient survival in children. The purpose of this study is to determine the safety of sirolimus monotherapy for long-term immunosuppression in children and adolescents after kidney transplantation.

This study will enroll 10 participants who previously completed the CCTPT-PC01 study. The accrual period is scheduled for 12 months. The study follow-up period will last 96 weeks. Patients from the CCTPT-PC01 study have been maintained on sirolimus and mycophenolate mofetil (MMF) since 2-3 months post transplant. Enrolled participants receiving (MMF) or Azathioprine at study entry will have their doses withdrawn gradually over a period of 6 months. Dosage will be reduced by 25% initially and by 25% every 2 months resulting in complete withdrawal by 6 months.

This study will consist of 11 study visits after screening and study entry. Study visits will occur at weeks 1, 8, 16, 24, 32, 40, 48, 60, 72, 84, and 96. A physical exam, vital signs, sirolimus levels, as well as blood and urine collection will occur at all visits. A renal biopsy will be performed at week 96.

Eligibility criteria: Inclusion Criteria:

* Participant and/or parent guardian able to understand and willing to provide informed consent
* Previously enrolled and completed the CCTPT-PC01 study and within the 36 months post-completion timeframe prior to study entry
* Currently receiving sirolimus and MMF or azathioprine therapy
* No history of acute rejection episodes
* No evidence of acute or chronic rejection on the 24 month CCTPT-PC01 protocol biopsy or any subsequent biopsy obtained after that time prior to study entry
* PRA (Class I and II) less than 5% at study entry
* No evidence of donor specific antibody at study entry
* Stable renal function with GFR greater than 60 cc/min 1.73M\^2 using the Schwartz calculated method
* A negative pregnancy test for female participants of childbearing potential at study entry
* Agreement by female and male participants to use FDA approved methods of contraception.

Exclusion Criteria:

* Total lymphocyte count less than 400 mm\^3
* Acute or chronic infection at study entry
* Treatment with investigational drug within 1 month prior to study entry
* Mental illness or history of drug or alcohol abuse that, in the opinion of the investigator, would interfere with the study
* History of allergic reaction to Iodine GFR assay
* History of malignancy within the past 12 months
* Inability or unwillingness to give informed consent or comply with the study protocol

Primary outcomes:
measure: Per-person incidence of acute rejection episodes and death or graft loss
timeFrame: Throughout study
Secondary outcomes:
measure: Incidence of chronic allograft dysfunction
timeFrame: Throughout study
measure: Incidence of sub-clinical rejection
timeFrame: Throughout study
measure: Incidence of hospitalizations
timeFrame: Throughout study
measure: Incidence of surgical complications
timeFrame: Throughout study
measure: Resumption of MMF or other therapy
timeFrame: Throughout study
measure: Incidence, severity, and treatment of anemia, hypertension, hyperlipidemia, proteinuria, thrombocytopenia, and leukopenia
timeFrame: Throughout study
measure: Incidence, severity, and treatment of opportunistic infections
timeFrame: Throughout study
measure: Incidence of biopsy proven PTLD
timeFrame: Throughout study
measure: Renal function assessed by measured GFR
timeFrame: At baseline, week 48 and week 96
measure: Development of donor-specific or non-specific anti-HLA antibodies
timeFrame: Throughout study
measure: Evolution of immune response in cellular, humoral, and molecular assays from baseline through week 96
timeFrame: Throughout study
Other outcomes:
Locations:
city: Madera
country: United States
facility: Children's Hospital of Central California
state: California
city: San Francisco
country: United States
facility: UCSF Children's Hospital
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 H. Harmon, MD
role: STUDY_CHAIR
References:
citation: McDonald RA, Smith JM, Ho M, Lindblad R, Ikle D, Grimm P, Wyatt R, Arar M, Liereman D, Bridges N, Harmon W; CCTPT Study Group. Incidence of PTLD in pediatric renal transplant recipients receiving basiliximab, calcineurin inhibitor, sirolimus and steroids. Am J Transplant. 2008 May;8(5):984-9. doi: 10.1111/j.1600-6143.2008.02167.x.
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.