Biomarkers for Post-Transplant Lymphoproliferative Disorders in Children

Study Overview
=================
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.

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

Conditions
-----------------
Heart Transplant, Small Intestine Transplant, Kidney Transplant, Liver Transplant, EBV-Related PTLD, PTLDs

Intervention / Treatment
-----------------
* Procedure: transplant
* Drug: Immunosuppressive Drugs


Participation Criteria
=================
Eligibility 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.

Ages Eligible for Study
-----------------
Maximum Age: 21 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Subjects Enrolled Pre-Transplant<br>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<br>* 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).<br>* Other names: transplantation;Drug: Immunosuppressive Drugs<br>* Immunosuppressive drugs prescribed as standard of care to prevent rejection of the allograft.<br>* Other names: Immunosuppressive Medications;|
| Subjects Enrolled Post-Transplant<br>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<br>* 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).<br>* Other names: transplantation;Drug: Immunosuppressive Drugs<br>* Immunosuppressive drugs prescribed as standard of care to prevent rejection of the allograft.<br>* 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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Biomarkers, Post-Transplant Lymphoproliferative Disorders (PTLDs)