Biomarkers for Post-Transplant Lymphoproliferative Disorders in Children

Completed

• Conditions: Small Intestine Transplant; Liver Transplant; PTLDs; Heart Transplant; Kidney Transplant; EBV-Related PTLD
• Interventions: Procedure: transplant; Drug: Immunosuppressive Drugs

• Registration Number: NCT02182986
• Lead Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

Brief Summary

Solid organ transplantation is an important therapeutic option for children with a variety of end stage diseases. However, the same immunosuppressive medications that are required to prevent the child's immune system from attacking and rejecting the transplanted organ can predispose these individuals to developing a very serious cancer that is linked to Epstein-Barr virus (EBV).

Detailed Description

EBV-associated post-transplant lymphoproliferative disease (PTLD) is the most common malignancy in children after transplant. Diagnosis and effective treatment of the EBV-associated cancer is hampered by our inability to determine which children are at risk of developing these cancers and to detect the cancer at an early stage. In this study, we plan to test new "biomarkers" in the blood of children that will tell us very early on if the child is at risk of developing the EBV-associated cancer or if the cancer is present. These studies provide new opportunities for detection, diagnosis, and treatment of children with EBV-associated, post-transplant cancer.

Study Timeline

• Study First Submitted: 2014-06-30
• Study First Submitted QC: 2014-07-07
• Study First Posted: 2014-07-08
• Study Start: 2014-08-14
• Primary Completion: 2019-05-15
• Study Completion: 2019-05-15
• Status Verified: 2019-08
• Last Update Submitted: 2019-08-28
• Last Update Posted: 2019-08-29

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 944

Inclusion Criteria

• Subject and/or parent or legal guardian must be able to understand and provide informed consent/assent;
• Candidate for or recipient of: heart, liver, heart with liver, small intestine, liver with small intestine, or kidney; and
• Subject enrolled within 3 years of transplant.

Exclusion Criteria

• Previous diagnosis of PTLD;
• Transplant recipients of lung alone, or in combination with an eligible organ type;
• Pancreas transplantation with the exception of 'en bloc' transplant in combined liver and small intestine multivisceral transplantation;
• Any combination other than listed in inclusion criteria;
• History of any previous solid organ, stem cell, or bone marrow transplantation;
• Inability or unwillingness of the legal guardian and/or the subject to comply with the study protocol.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Subjects Enrolled Pre-Transplant	Immunosuppressive Drugs	Subjects (N=approximately 357) Enrolled Pre-Transplant * Subjects with evidence of EBV infection prior to transplant * Subjects without evidence of EBV infection prior to transplant, who are at risk of developing EBV infection after transplant
Subjects Enrolled Post-Transplant	transplant	Subjects (N=approximately 588) Enrolled 3 Yrs Post-Transplant * Subjects with evidence of EBV infection prior to transplant * Subjects without evidence of EBV infection prior to transplant, who are at risk of developing EBV infection after transplant
Subjects Enrolled Pre-Transplant	transplant	Subjects (N=approximately 357) Enrolled Pre-Transplant * Subjects with evidence of EBV infection prior to transplant * Subjects without evidence of EBV infection prior to transplant, who are at risk of developing EBV infection after transplant
Subjects Enrolled Post-Transplant	Immunosuppressive Drugs	Subjects (N=approximately 588) Enrolled 3 Yrs Post-Transplant * Subjects with evidence of EBV infection prior to transplant * Subjects without evidence of EBV infection prior to transplant, who are at risk of developing EBV infection after transplant

Primary Outcome Measures

Name	Time	Method
Incidence of Epstein-Barr Virus (EBV) Positive Post-Transplant Lymphoproliferative Disorders (PTLD)	Receipt of transplanted organ(s) to confirmation of EBV-positive PTLD, up to year 4 post - enrollment	The development of EBV positive PTLD during the study period as assessed by the local site pathologist, with confirmation of the PTLD diagnosis by the Study Clinicopathological Review Board (SCPRB)
Specified Gain-of-Function Mutations in EBV Latent Membrane Protein 1 (LMP-1)	Receipt of transplanted organ(s) to confirmation of mutations in EBV LMP1 , up to year 4 post - enrollment	Specified gain-of-function mutations in EBV LMP-1 (e.g., corresponding to EBV LMP-1 variants G212S or S366T) detected by polymerase chain reaction (PCR) method
Pathogenic Changes in B Cell Clonotype Development	Receipt of transplanted organ(s) to confirmation of changes in B cell clonotype development, up to year 4 post - enrollment	Pathogenic changes in B cell clonotype development as assessed using high throughput sequencing (HTS)

Trial Locations

Locations (7)

Medstar Georgetown Transplant Institute; 🇺🇸 Washington, District of Columbia, United States

Lucile Packard Children's Hospital Stanford; 🇺🇸 Stanford, California, United States

Cincinnati Children's Hospital Medical Center; 🇺🇸 Cincinnati, Ohio, United States

University of California, Los Angeles; 🇺🇸 Los Angeles, California, United States

Children's Hospital of Pittsburgh of UPMC; 🇺🇸 Pittsburgh, Pennsylvania, United States

University of Texas Southwestern; 🇺🇸 Dallas, Texas, United States

University of Miami Health System; 🇺🇸 Miami, Florida, United States