This is a prospective multicenter, open-label, single-arm trial in which 20 pediatric recipients of parental living-donor liver allografts will undergo gradual withdrawal of immunosuppression with the goal of complete withdrawal. Patients on stable immunosuppression regimens with good organ function and no evidence of acute or chronic rejection or other forms of allograft dysfunction will be enrolled. Participants will undergo gradual withdrawal of immunosuppression and will be followed for a minimum of 4 years after completion of immunosuppression withdrawal. Immunologic and genetic profiles will be collected at multiple time points and compared between tolerant and nontolerant participants.

Plan to Share IPD: Yes Plan Description: Participant level data and additional study materials are available to the public in: 1.) the Immunology Database and Analysis Portal (ImmPort), a long-term archive of clinical and mechanistic data from Division of Allergy, Immunology, and Transplantation (DAIT)-funded grants and contracts and 2.) TrialShare, the Immune Tolerance Network (ITN) Clinical Trials Research Portal.

instance of dataset

available with registration

WISP-R

National Institute of Allergy and Infectious Diseases (NIAID)

Drug: Gradual withdrawal of immunosuppressive medication With high dose, daily dose reduction by 25% for 8 weeks. With low dose, daily dose reduction by 25% for 4 weeks.

registration required

Liver Transplant Immunosuppression

Sandy Feng, MD

University of California, San Francisco

Principal Investigator

Withdrawal of Immunosuppression in Pediatric Liver Transplant Recipients

20

Proportion of Subjects Successfully Withdrawn From Immunosuppression [ Time Frame: 1 year after completion of immunosuppression withdrawal ] Subjects were considered successfully withdrawn from immunosuppression if they remained off immunosuppression for at least one year with normal allograft function Proportion of Patients Who Suffer Graft Loss or Die Following Initiation of Immunosuppression Withdrawal [ Time Frame: 1 year ]

Time From Start of Immunosuppression to the First Episode of Acute Rejection or to Diagnosis of Chronic Rejection [ Time Frame: Immunosuppression to first acute rejection or diagnosis of chronic rejection ] Distribution of Histologic Severity Among Rejection Episodes [ Time Frame: Immunosuppression to rejection ] Incidence of Adverse Events [ Time Frame: throughout trial ] Changes in Renal Function, Blood Pressure, Cholesterol Level, and Glucose Control [ Time Frame: throughout trial ]

NC

Inclusion Criteria for Liver Recipients: Received liver from living parent donor Received transplant at least 4 years prior to study entry Less than 18 years of age at time of transplant Parent or guardian willing to provide informed consent Inclusion Criteria for Liver Donors: Willing to participate in this study Exclusion Criteria for Liver Recipients: Underwent transplant because of liver failure related to autoimmune disease Underwent transplant of a second organ simultaneously with or after liver transplant OR liver retransplantation Receiving immunosuppression with more than one drug 50% increase in dose of current immunosuppressive drug HIV infection Hepatitis B or C virus infection Pregnancy or breastfeeding

2010-08-01

Immunosuppression Withdrawal for Pediatric Living-donor Liver Transplant Recipients (ITN029ST)

Experimental: Immunosuppression Withdrawal Recipients of parental living donor liver transplants 4 or more years prior to trial enrollment, who also had stable allograft function during the preceding 6 months while taking a single immunosuppressive drug were permitted to undergo withdrawal of immunosuppression therapy. With high dose, daily dose reduction by 25% for 8 weeks. With low dose, daily dose reduction by 25% for 4 weeks. Patients are carefully evaluated/monitored throughout the study by assessments including but not limited to liver biopsy, liver tests and clinic visits, alloantibodies, autoantibodies and quantitative immunoglobulin G test results. Intervention: Drug: Gradual withdrawal of immunosuppressive medication

Antirejection medicines, also known as immunosuppressive drugs, are prescribed to organ transplant recipients to prevent their bodies from rejecting the new organ. Long-term use of these drugs places transplant recipients at higher risk of serious infections and certain types of cancer. The purpose of this study is to determine whether immunosuppressive drugs can be safely withdrawn over a minimum of 9 months from children who received liver transplants at least 4 years ago.

In order to prevent the rejection of transplanted organs, transplant recipients are prescribed a strict, lifelong regimen of immunosuppressive drugs. While these drugs help prevent the body from rejecting the transplant, they carry numerous complications, including increased risk of serious infections and certain types of cancer. However, there is mounting evidence that a significant percentage of liver transplant recipients can maintain a healthy, functioning transplant without ongoing immunosuppression. This study will determine whether gradual withdrawal and eventual discontinuation of all immunosuppressive medication can be safely accomplished in children who received a liver transplant from a parent. Twenty eligible patients who were under 18 years old at the time of transplant, whose donor was a parent, and who received the transplant at least four years ago will be enrolled in the study. Liver recipients will have an initial screening assessment consisting of a medical history, liver biopsy, and urine and blood collection. Eligible recipients will be placed on a modified medication schedule to gradually decrease their immunosuppression medication slowly over a 9- to 12-month period, during which time they will be closely monitored by study staff. Immunosuppressive drugs will not be provided by this study. For a minimum of 3 and up to a maximum of 7 years, monthly telephone consultations and quarterly study visits will occur. Visits will include physical exams and blood collection to monitor the children's health during the withdrawal phase. The exact schedule of immunosuppressant withdrawal will be determined by study physicians based on participant's health and immune function test results. Donor and nondonor parents will be asked to each provide one blood sample during the initial study visits for immunologic and genetic testing. *** IMPORTANT NOTICE: *** The National Institute of Allergy and Infectious Diseases and the Immune Tolerance Network do not recommend the discontinuation of immunosuppressive therapy for recipients of cell, organ, or tissue transplants outside of physician-directed, controlled clinical studies. Discontinuation of prescribed immunosuppressive therapy can result in serious health consequences and should only be performed in certain rare circumstances, upon the recommendation and with the guidance of your health care provider.

Intervention Model: Single Group Assignment Intervention Model Description: Recipients of parental living-donor liver allografts will undergo gradual withdrawal as tolerated of immunosuppression with the goal of complete withdrawal. Masking: None (Open Label) Primary Purpose: Treatment

United States

2006-05-01

ITN TrialShare