Biomarkers for Post-Transplant Lymphoproliferative Disorders in Children

Biomarkers for Post-Transplant Lymphoproliferative Disorders in Children (CTOTC-06)

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).

Study Overview

• Status: Completed
• Conditions: Liver Transplant; Kidney Transplant; Heart Transplant; EBV-Related PTLD; Small Intestine Transplant; PTLDs
• Intervention / Treatment: Procedure: transplant; Drug: Immunosuppressive Drugs

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 Type: Observational
• Enrollment (Actual): 944

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90095
      • University of California, Los Angeles
    • Stanford, California, United States, 94305
      • Lucile Packard Children's Hospital Stanford
  • District of Columbia
    • Washington, District of Columbia, United States, 20057
      • Medstar Georgetown Transplant Institute
  • Florida
    • Miami, Florida, United States, 33101
      • University of Miami Health System
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Cincinnati Children's Hospital Medical Center
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15224
      • Children's Hospital of Pittsburgh of UPMC
  • Texas
    • Dallas, Texas, United States, 75235
      • University of Texas Southwestern

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 21 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Pediatric Candidates for or recipients of heart, liver, heart with liver, kidney, small intestine, or liver with small intestine at participating major pediatric solid organ transplant programs

Description

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 Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Subjects Enrolled Pre-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	Procedure: transplant; All subjects enrolled in this study are candidates for/recipients of solid organ transplants as a therapeutic for end stage diseases (e.g., heart, liver, heart with liver, kidney, small intestine, or liver with small intestine transplants).; Other Names: transplantation; Drug: Immunosuppressive Drugs; Immunosuppressive drugs prescribed as standard of care to prevent rejection of the allograft.; Other Names: Immunosuppressive Medications
Subjects Enrolled Post-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	Procedure: transplant; All subjects enrolled in this study are candidates for/recipients of solid organ transplants as a therapeutic for end stage diseases (e.g., heart, liver, heart with liver, kidney, small intestine, or liver with small intestine transplants).; Other Names: transplantation; Drug: Immunosuppressive Drugs; Immunosuppressive drugs prescribed as standard of care to prevent rejection of the allograft.; Other Names: Immunosuppressive Medications

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Epstein-Barr Virus (EBV) Positive Post-Transplant Lymphoproliferative Disorders (PTLD)	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)	Receipt of transplanted organ(s) to confirmation of EBV-positive PTLD, up to year 4 post - enrollment
Specified Gain-of-Function Mutations in EBV Latent Membrane Protein 1 (LMP-1)	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	Receipt of transplanted organ(s) to confirmation of mutations in EBV LMP1 , up to year 4 post - enrollment
Pathogenic Changes in B Cell Clonotype Development	Pathogenic changes in B cell clonotype development as assessed using high throughput sequencing (HTS)	Receipt of transplanted organ(s) to confirmation of changes in B cell clonotype development, up to year 4 post - enrollment

Collaborators and Investigators

• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Collaborators: Clinical Trials in Organ Transplantation in Children
• Investigators: Principal Investigator: Carlos Esquivel, M.D., Ph.D., Stanford University; Study Chair: Daniel Bernstein, M.D., Stanford University

Publications and helpful links

Helpful Links

• National Institute of Allergy and Infectious Diseases (NIAID)
• Clinical Trials in Organ Transplantation in Children (CTOT-C)

Study record dates

Study Major Dates

• Study Start (Actual): August 14, 2014
• Primary Completion (Actual): May 15, 2019
• Study Completion (Actual): May 15, 2019

Study Registration Dates

• First Submitted: June 30, 2014
• First Submitted That Met QC Criteria: July 7, 2014
• First Posted (Estimate): July 8, 2014

Study Record Updates

• Last Update Posted (Actual): August 29, 2019
• Last Update Submitted That Met QC Criteria: August 28, 2019
• Last Verified: August 1, 2019

More Information

Terms related to this study

• Keywords: Biomarkers; Post-Transplant Lymphoproliferative Disorders (PTLDs)
• Additional Relevant MeSH Terms: Immune System Diseases; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoproliferative Disorders; Physiological Effects of Drugs; Immunologic Factors; Immunosuppressive Agents
• Other Study ID Numbers: DAIT CTOTC-06