A Study of Experimetnal Tabelecleucel After Failed Standard Treatment for Solid Organ Transplants With Epstein-Barr Virus

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Age: -1 years or older
Gender:
Any
Healthy Volunteers: No
Keywords: organ transplant, Epstein-Barr Virus, Post-Transplant Lymphoproliferative Disease, chemotherapy failure
Type: Biological study, Phase 3
Target:
66 Participants
Investigator:
Description
This is a research study for patients with EBV-associated Post-Transplant Lymphoproliferative Disorder (EBV-PTLD). The study is for patients after a solid organ transplant (SOT) that didn’t respond to rituximab therapy with or without chemotherapy. This study will use a new treatment called tabelecleucel (also known as ATA129).

Epstein-Barr Virus (EBV) is the virus that causes mononucleosis, also known as “mono”. Almost all adults have had EBV. For most people, EBV never causes a health problem. For people whose immune system is not working properly EBV can cause certain diseases where cells grow abnormally. This may happen in people who have had a transplant and those who have immune disorders.

EBV-associated Post-Transplant Lymphoproliferative Disease (EBV-PTLD) can occur after a solid organ transplant (SOT). EBV infects immune cells in your blood, called B cells. In patients who have had an SOT, their immune system is suppressed because of the transplant. These infected immune cells can become cancerous.

This research study is for patients who have EBV-PTLD following an SOT. It has not responded well to treatment with rituximab or rituximab and chemotherapy. Participants will receive experimetnal tabelecleucel. This is a product containing special immune allogeneic cells. The cells are called EBV-Cytotoxic T Lymphocytes (EBV-CTLs). They are made in the laboratory starting with cells from a healthy person who is immune to EBV. Your treatment will be selected specifically for you from a library of frozen tabelecleucel. It will be matched using certain human leukocyte antigens (HLAs).

Treatment with tabelecleucel is experimental and is not approved by the FDA for use in the general public. It has been approved for testing in clinical trials.

Tabelecleucel is made by taking donor cells from a healthy person. The cells that fight EBV (EBVCTLs) are grown in a laboratory for several weeks. They are then stored in a freezer until they are matched to a patient needing treatment. The cells are not genetically modified. This process is repeated using multiple donors in order to create a library of tabelecleucel products.
This study requires

The study team will make sure you qualify to take part in the study. Qualified participants will receive detailed information about the study. This may include a list of study-related tests and procedures.

Who can participate

Inclusion criteria:

  1. Prior SOT of kidney, liver, heart, lung, pancreas, small bowel, or any combination of these
  2. A diagnosis of locally-assessed, biopsy-proven EBV+ PTLD with a pathology sample available for central review
  3. Availability of appropriate HLA partially-matched and restricted tabelecleucel cell product
  4. Measurable, 18F-deoxyglucose (FDG)-avid (Deauville score >= 3) systemic disease (using Lugano Classification response criteria) by positron emission tomography (PET)-diagnostic computed tomography (CT). For subjects with treated central nervous system (CNS) disease, a head CT and/or brain/spinal magnetic resonance imaging (MRI) as clinically appropriate will be required to follow CNS disease response per Lugano Classification response criteria.
  5. Treatment failure of rituximab monotherapy (Cohort A) or rituximab plus any concurrent or sequentially administered chemotherapy regimen (Cohort B) for treatment of PTLD. Note: Subjects with CD20 negative disease are eligible to enroll without prior anti-CD20 therapy after failure of first-line treatment (reduction of immunosuppression is not considered first-line therapy) and discussion with the sponsor's medical monitor.
  6. Males and females of any age
  7. Eastern Cooperative Oncology Group (ECOG) performance status <= 3 for subjects aged > 16 years; Lansky score >= 20 for subjects from birth to 16 years
  8. Adequate organ function
  9. Absolute neutrophil count >= 1000/μL, with or without cytokine support
  10. Platelet count >= 50,000/μL, with or without transfusion or cytokine support
  11. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin (TBILI) each < 3×ULN; however, ALT, AST, and TBILI each <= 5×ULN is acceptable if the elevation is considered due to PTLD involvement of the liver.
  12. Creatinine < 3×ULN
  13. Subject or subject's representative is willing and able to provide written informed consent

Exclusion criteria:

  1. Daily steroids of > 0.5 mg/kg prednisone or glucocorticoid equivalent, methotrexate, or extracorporeal photopheresis
  2. Untreated CNS PTLD or CNS PTLD for which the subject is actively receiving treatment at enrollment
  3. Grade >= 2 graft-versus-host disease (GvHD) per the Center for International Blood and Marrow Transplant Research (CIBMTR) consensus grading system at enrollment
  4. Ongoing or recent use of a checkpoint inhibitor agent (eg ipilimumab, pembrolizumab, nivolumab) within three drug half-lives from the most recent dose to Cycle 1 Day 1
  5. Need for vasopressor or ventilatory support
  6. Antithymocyte globulin or similar anti-T cell antibody therapy <= 4 weeks prior to Cycle 1 Day 1
  7. Treatment with Epstein-Barr virus cytotoxic T lymphocytes or chimeric antigen receptor (CAR) T cells directed against B cells within 8 weeks of Cycle 1 Day 1
  8. Pregnancy
  9. Female of childbearing potential or male with a female partner of childbearing potential unwilling to use a highly effective method of contraception
  10. Inability to comply with study-related procedures
Benefits and risks of participating
BENEFITS:

We cannot promise any benefits to you as a result of taking part in this research study.


RISKS:

The study doctor will discuss the risks associated with taking part in this research study.
Compensation
You will not be paid to take part in this research study.
Resources
Schedule
Study duration and period
Overall the research study will take about 5 years to complete.
Recruitment period
From Nov. 13, 2018
Location
UC Davis Comprehensive Cancer Center
4501 X Street
Sacramento, CA 95817
Contact
Christina Romo
Research Topic
Conditions:
  • Epstein-Barr Virus-Related Post-Transplant Lymphoproliferative Disorder