Detection and Cytotoxic T Lymphocyte Therapy of Post-Transplant Lymphoproliferative Disorder After Liver Transplant

This study has been completed.
Sponsor:
Information provided by:
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
ClinicalTrials.gov Identifier:
NCT00063648
First received: July 1, 2003
Last updated: January 12, 2010
Last verified: January 2010
  Purpose

Despite advances in medical and gene therapy, orthotopic liver transplantation remains the only definitive therapeutic option for children with end-stage liver disease. Recent advances in pre-, intra-, and early post-transplant care have resulted in a dramatic improvement in survival of the pediatric liver transplant patient. The broad long-range goal of our research program is directed at enhancing the patient's long-term survival. Our primary focus relates to obligate life-long immunosuppression, with its inherent complications including severe infection and development of cancer. These two complications come together in a single disease, Epstein-Barr Virus (EBV)- associated post-transplant lymphoproliferative disorder (PTLD). EBV, a latent human lymphotrophic herpes virus infects and immortalizes B cells. Primary infection usually occurs via salivary exchange and results in a mild, self-limited illness followed by life-long EBV-specific T cell controlled EBV latency. T cell-based immunosuppression prevents allograft rejection, however, it also suppresses cytotoxic T lymphocyte (CTL) function, generating an environment in which EBV-infected cells can proliferate. Patients receiving life-long T cell-based immunosuppression have an increased risk of developing PTLD due to their inability to produce normal immunoregulatory responses. This disease is particularly devastating to the pediatric patient as its incidence is at least 4-fold greater than in the adult liver transplant patient population. In fact, PTLD is the number one cause of death following pediatric liver transplantation. At this time, there is no definitive method of prospectively detecting, diagnosing, or treating PTLD, and current treatment protocols place the liver allograft and patient at risk. Therefore, a diagnostic tool that is both sensitive and specific, and a treatment strategy with low toxicity are greatly needed to decrease the morbidity and mortality suffered by the pediatric liver transplant patient with PTLD. Our proposed studies will support our hypothesis that the combination of a persistently elevated EBV load in the setting of a diminished immune response to EBV will be an early risk indicator associated with PTLD development, and that pre-emptive treatment utilizing autologous adoptive EBV-specific CTL immunotherapy will provide a low toxicity treatment option.


Condition Intervention Phase
Liver Disease
Lymphoproliferative Disorders
Biological: EBV-specific autologous CTL
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Prevention

Resource links provided by NLM:


Further study details as provided by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK):

Estimated Enrollment: 50
Study Start Date: May 2002
Estimated Study Completion Date: December 2007
  Eligibility

Ages Eligible for Study:   1 Month to 21 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Pediatric patients s/p orthotopic liver transplantation

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00063648

Locations
United States, Texas
Texas Children's Hospital
Houston, Texas, United States, 77030
Sponsors and Collaborators
  More Information

No publications provided

ClinicalTrials.gov Identifier: NCT00063648     History of Changes
Other Study ID Numbers: PTLD (completed)
Study First Received: July 1, 2003
Last Updated: January 12, 2010
Health Authority: United States: Federal Government

Keywords provided by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK):
PTLD
CTL Therapy
Post-transplant lymphoproliferative disorder

Additional relevant MeSH terms:
Disease
Liver Diseases
Lymphoproliferative Disorders
Pathologic Processes
Digestive System Diseases
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases

ClinicalTrials.gov processed this record on September 18, 2014