Biomarkers for Post-Transplant Lymphoproliferative Disorders in Children

• ClinicalTrials.gov Identifier: NCT02182986
• Recruitment Status: Completed
• First Posted: July 8, 2014
• Last Update Posted: August 29, 2019
• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Collaborator: Clinical Trials in Organ Transplantation in Children
• Information provided by (Responsible Party): National Institute of Allergy and Infectious Diseases (NIAID)

Study Description

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).

Condition or disease	Intervention/treatment
Heart Transplant; Small Intestine Transplant; Kidney Transplant; Liver Transplant; EBV-Related PTLD; PTLDs	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 Design

• Study Type: Observational
• Actual Enrollment: 944 participants
• Observational Model: Case-Control
• Time Perspective: Prospective
• Official Title: Biomarkers for Post-Transplant Lymphoproliferative Disorders in Children (CTOTC-06)
• Actual Study Start Date: August 14, 2014
• Actual Primary Completion Date: May 15, 2019
• Actual Study Completion Date: May 15, 2019

Groups and Cohorts

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 Name: transplantation; Drug: Immunosuppressive Drugs; Immunosuppressive drugs prescribed as standard of care to prevent rejection of the allograft.; Other Name: 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 Name: transplantation; Drug: Immunosuppressive Drugs; Immunosuppressive drugs prescribed as standard of care to prevent rejection of the allograft.; Other Name: Immunosuppressive Medications

Outcome Measures

Primary Outcome Measures :

1. Incidence of Epstein-Barr Virus (EBV) Positive Post-Transplant Lymphoproliferative Disorders (PTLD) [ Time Frame: 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)
2. Specified Gain-of-Function Mutations in EBV Latent Membrane Protein 1 (LMP-1) [ Time Frame: 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
3. Pathogenic Changes in B Cell Clonotype Development [ Time Frame: 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)

Biospecimen Retention:   Samples With DNA

Blood and tissue samples.

Eligibility Criteria

• Ages Eligible for Study: up to 21 Years (Child, Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No
• 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

Criteria

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.

Contacts and Locations

Locations

United States, California

University of California, Los Angeles

Los Angeles, California, United States, 90095

Lucile Packard Children's Hospital Stanford

Stanford, California, United States, 94305

United States, District of Columbia

Medstar Georgetown Transplant Institute

Washington, District of Columbia, United States, 20057

United States, Florida

University of Miami Health System

Miami, Florida, United States, 33101

United States, Ohio

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States, 45229

United States, Pennsylvania

Children's Hospital of Pittsburgh of UPMC

Pittsburgh, Pennsylvania, United States, 15224

United States, Texas

University of Texas Southwestern

Dallas, Texas, United States, 75235

Sponsors and Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)

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

More Information

Additional Information:

National Institute of Allergy and Infectious Diseases (NIAID) 

Clinical Trials in Organ Transplantation in Children (CTOT-C) 

• Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
• ClinicalTrials.gov Identifier: NCT02182986
• Other Study ID Numbers: DAIT CTOTC-06
• First Posted: July 8, 2014
• Last Update Posted: August 29, 2019
• Last Verified: August 2019

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):

Biomarkers; Post-Transplant Lymphoproliferative Disorders (PTLDs)

Additional relevant MeSH terms:

Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs