Safety of Immunosuppression Minimization in Children and Adolescents After Kidney Transplantation

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00768729
First received: October 6, 2008
Last updated: February 14, 2013
Last verified: February 2013
  Purpose

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.


Condition Intervention Phase
Kidney Failure, Chronic
Kidney Transplantation
Immunosuppression
Drug: Sirolimus
Drug: MMF or Azathioprine
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: Immunosuppression Minimization to Single Drug Therapy With Sirolimus (Rapamune) in Pediatric Transplantation

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcome Measures:
  • Per-person incidence of acute rejection episodes and death or graft loss [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Incidence of chronic allograft dysfunction [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]
  • Incidence of sub-clinical rejection [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]
  • Incidence of hospitalizations [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]
  • Incidence of surgical complications [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]
  • Resumption of MMF or other therapy [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
  • Incidence, severity, and treatment of anemia, hypertension, hyperlipidemia, proteinuria, thrombocytopenia, and leukopenia [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]
  • Incidence, severity, and treatment of opportunistic infections [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]
  • Incidence of biopsy proven PTLD [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]
  • Renal function assessed by measured GFR [ Time Frame: At baseline, week 48 and week 96 ] [ Designated as safety issue: No ]
  • Development of donor-specific or non-specific anti-HLA antibodies [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
  • Evolution of immune response in cellular, humoral, and molecular assays from baseline through week 96 [ Time Frame: Throughout study ] [ Designated as safety issue: No ]

Enrollment: 7
Study Start Date: May 2009
Study Completion Date: December 2012
Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1

Participants who have been maintained on MMF at study entry will start the study on 600 mg/m2 MMF orally daily. Participants who have been maintained on Azathioprine due to MMF intolerance will receive 1 mg/kg Azathioprine orally daily.

Participants will continue receiving sirolimus throughout the study. However, MMF or Azathioprine will be withdrawn gradually over a period of at least 6 months. Dosage will be reduced by 25% initially and by 25% every subsequent 2 months resulting in complete withdrawal by 6 months.

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.
Other Name: Rapamycin, Rapamune
Drug: 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.

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

Ages Eligible for Study:   1 Year to 20 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00768729

Locations
United States, California
Children's Hospital of Central California
Madera, California, United States
UCSF Children's Hospital
San Francisco, California, United States
United States, Massachusetts
Children's Hospital, Boston
Boston, Massachusetts, United States
United States, Pennsylvania
Children's Hospital, Philadelphia
Philadelphia, Pennsylvania, United States
United States, Washington
Children's Hospital and Regional Medical Center, Seattle
Seattle, Washington, United States
Sponsors and Collaborators
Investigators
Study Chair: William H. Harmon, MD Children's Hospital Boston
  More Information

Additional Information:
Publications:
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00768729     History of Changes
Other Study ID Numbers: DAIT CTOTC-01
Study First Received: October 6, 2008
Last Updated: February 14, 2013
Health Authority: United States: Federal Government

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
End stage renal disease
Kidney transplantation
Renal transplantation
Kidney failure
Children
Adolescents
Sirolimus
Rapamycin
CellCept
Mycophenolate mofetil (MMF)
Azathioprine

Additional relevant MeSH terms:
Kidney Failure, Chronic
Renal Insufficiency
Renal Insufficiency, Chronic
Kidney Diseases
Urologic Diseases
Azathioprine
Sirolimus
Everolimus
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antimetabolites, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antibiotics, Antineoplastic
Antifungal Agents
Anti-Infective Agents
Anti-Bacterial Agents

ClinicalTrials.gov processed this record on July 26, 2014