Safety of Immunosuppression Minimization in Children and Adolescents After Kidney Transplantation

Kidney Transplantation Clinical Trial

Official title:

Immunosuppression Minimization to Single Drug Therapy With Sirolimus (Rapamune) in Pediatric Transplantation

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00768729
• Other study ID #: DAIT CTOTC-01
• Status: Completed
• Phase: Phase 1
• First received: October 6, 2008
• Last updated: February 14, 2013
• Start date: May 2009
• Est. completion date: December 2012

Study information

• Verified date: February 2013
• 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

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.

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 Enrolled participants receiving (MMF) or Azathioprine at study entry will have their doses withdrawn gradually over a period of 6 months.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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 7
• Est. completion date: December 2012
• Est. primary completion date: December 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 1 Year to 20 Years

Eligibility

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

Study Design

Allocation: Non-Randomized, 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:
• Sirolimus
Oral tablets or liquid taken every 12 hours. Dosage adjusted to attain target trough levels of 8-12 ng/mL. Participants who have maintained such levels at study entry on once daily dosage will be permitted to continue on once daily dosing.
• MMF or Azathioprine
600 mg/m2 MMF taken orally daily or Azathioprine orally daily. Dosage of Azathioprine is dependent on weight. MMF or Azathioprine will be reduced by 25% initially and by 25% every 2 months resulting in complete withdrawal by 6 months.

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)

Country where clinical trial is conducted

United States, 

References & Publications (2)

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. — 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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Per-person incidence of acute rejection episodes and death or graft loss		Throughout study	Yes
Secondary	Incidence of chronic allograft dysfunction		Throughout study	Yes
Secondary	Incidence of sub-clinical rejection		Throughout study	Yes
Secondary	Incidence of hospitalizations		Throughout study	Yes
Secondary	Incidence of surgical complications		Throughout study	Yes
Secondary	Resumption of MMF or other therapy		Throughout study	No
Secondary	Incidence, severity, and treatment of anemia, hypertension, hyperlipidemia, proteinuria, thrombocytopenia, and leukopenia		Throughout study	Yes
Secondary	Incidence, severity, and treatment of opportunistic infections		Throughout study	Yes
Secondary	Incidence of biopsy proven PTLD		Throughout study	Yes
Secondary	Renal function assessed by measured GFR		At baseline, week 48 and week 96	No
Secondary	Development of donor-specific or non-specific anti-HLA antibodies		Throughout study	No
Secondary	Evolution of immune response in cellular, humoral, and molecular assays from baseline through week 96		Throughout study	No

External Links

•   CTOTC Website