Tabelecleucel for Solid Organ or Allogeneic Hematopoietic Cell Transplant Participants With Epstein-Barr Virus-Associated Post-Transplant Lymphoproliferative Disease (EBV+ PTLD) After Failure of Rituximab or Rituximab and Chemotherapy
Hematopoietic Malignancies
Solid Tumor
0 Years and older, Male and Female
ATA129-EBV-302 (primary)
NCI-2018-00043
Summary
The purpose of this study is to determine the clinical benefit and characterize the
safety profile of tabelecleucel for the treatment of Epstein-Barr virus-associated
post-transplant lymphoproliferative disease (EBV+ PTLD) in the setting of (1) solid organ
transplant (SOT) after failure of rituximab and rituximab plus chemotherapy or (2)
allogeneic hematopoietic cell transplant (HCT) after failure of rituximab.
Objectives
This is a multicenter, open-label, phase 3 study to assess the efficacy and safety of
tabelecleucel for the treatment of EBV+ PTLD in the setting of SOT after failure of
rituximab and rituximab plus chemotherapy (SOT cohort) or HCT after failure of rituximab
(HCT cohort).
Enrollment will be preceded by confirmation of availability of partially human leukocyte
antigen (HLA) matched and restricted tabelecleucel for the participant.
Study procedures and product administration will be the same for each cohort.
Tabelecleucel will be administered in cycles lasting 5 weeks (35 days). During each
cycle, participants will receive intravenous tabelecleucel at a dose of 2×10^6 cells/kg
on Days 1, 8, and 15, followed by observation through Day 35. Treatment will continue
until maximal response, unacceptable toxicity, initiation of non protocol therapy, or
failure of tabelecleucel with up to 2 different HLA restrictions (SOT cohort) or up to 4
different HLA restrictions (HCT cohort). The study includes a total of 5 years of
follow-up for disease and survival status.
This protocol has been amended to include the HCT cohort from clinical study
ATA129-EBV-301 (NCT03392142).
NOTE, 29 April 2020: Enrollment is temporarily paused at study site/locations with status
"active, not recruiting" due to COVID-19 restrictions.
Eligibility
- Prior SOT of kidney, liver, heart, lung, pancreas, small bowel, or any combination of these (SOT cohort); or prior allogeneic HCT (HCT cohort)
- A diagnosis of locally-assessed, biopsy-proven EBV+ PTLD
- Availability of appropriate partially HLA-matched and restricted tabelecleucel has been confirmed by the sponsor
- Measurable, 18F-deoxyglucose (FDG)-avid (Deauville score = 3) systemic disease using Lugano Classification response criteria by positron emission tomography (PET)-diagnostic computed tomography (CT), except when contraindicated or mandated by local practice, then magnetic resonance imaging (MRI) may be used.For subjects with treated central nervous system (CNS) disease, a head CT and/or brain/spinal MRI as clinically appropriate will be required to follow CNS disease response per Lugano Classification response criteria.
- Treatment failure of rituximab or interchangeable commercially available biosimilar monotherapy (SOT subgroup A or HCT cohort) or rituximab plus any concurrent or sequentially administered chemotherapy regimen (SOT subgroup B) for treatment of PTLD.
- Eastern Cooperative Oncology Group performance status = 3 for subjects aged = 16 years; Lansky score = 20 for subjects < 16 years
- For HCT cohort only: If allogeneic HCT was performed as treatment for an acute lymphoid or myeloid malignancy, the underlying primary disease for which the subject underwent transplant must be in morphologic remission
- Adequate organ function
- Absolute neutrophil count = 1000/µL, (SOT cohort) or = 500/µL (HCT cohort), with or without cytokine support
- Platelet count = 50,000/µL, with or without transfusion or cytokine support. For HCT cohort, platelet count < 50,000/µL but = 20,000/µL, with or without transfusion support, is permissible if the subject has not had grade = 2 bleeding in the prior 4 weeks (where grading of the bleeding is determined per the National Cancer Institute's Common Terminology Criteria for Adverse Events [CTCAE], version 5.0)
- Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin each < 5 × the upper limit of normal; however, ALT, AST, and total bilirubin each = 10 × upper limit of normal is acceptable if the elevation is considered by the investigator to be due to EBV and/or PTLD involvement of the liver as long as there is no known evidence of significant liver dysfunction
- Subject or subject's representative is willing and able to provide written informed consent
Treatment Sites in Georgia
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