Safety of Immunosuppression Minimization in Children and Adolescents After Kidney Transplantation

NCT00768729 | Completed Phase 1 DMC

• 1 other identifier: DAIT CTOTC-01
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 5

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.

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

Outcome Measures

Primary Outcomes (1)

• Per-person incidence of acute rejection episodes and death or graft loss

  Throughout study

Secondary Outcomes (11)

• Incidence of chronic allograft dysfunction

  Throughout study

• Incidence of sub-clinical rejection

  Throughout study

• Incidence of hospitalizations

  Throughout study

• Incidence of surgical complications

  Throughout study

• Resumption of MMF or other therapy

  Throughout study

Study Arms (1)

1

EXPERIMENTAL

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 However, MMF or Azathioprine will be withdrawn gradually over a period of at least 6 months.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; Drug: MMF or Azathioprine

Interventions

Sirolimus DRUG

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.

Also known as: Rapamycin, Rapamune

1

MMF or Azathioprine DRUG

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.

1

Eligibility Criteria

• Age: 1 Year - 20 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (5)

Children's Hospital of Central California

Madera, California, United States

Location

UCSF Children's Hospital

San Francisco, California, United States

Location

Children's Hospital, Boston

Boston, Massachusetts, United States

Location

Children's Hospital, Philadelphia

Philadelphia, Pennsylvania, United States

Location

Children's Hospital and Regional Medical Center, Seattle

Seattle, Washington, United States

Location

Related 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.

  PMID: 18416737 BACKGROUND

• 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.

  PMID: 15888040 BACKGROUND

Related Links

• CTOTC Website

MeSH Terms

Conditions

Kidney Failure, Chronic; Renal Insufficiency

Interventions

Sirolimus; Azathioprine

Condition Hierarchy (Ancestors)

Renal Insufficiency, Chronic; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals; Thionucleosides; Sulfur Compounds; Mercaptopurine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• William H. Harmon, MD

  Boston Children's Hospital

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 6, 2008
• First Posted: October 8, 2008
• Study Start: May 1, 2009
• Primary Completion: December 1, 2012
• Study Completion: December 1, 2012
• Last Updated: February 15, 2013

Record last verified: 2013-02

Locations

US (5)