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

Eligibility Criteria

• 1. Prior SOT of kidney, liver, heart, lung, pancreas, small bowel, or any combination of these (C-SOT); or prior allogeneic HCT (C-HCT)
• 2. A diagnosis of locally assessed, biopsy-proven EBV+ PTLD
• 3. Availability of appropriate partially HLA-matched and restricted tabelecleucel has been confirmed by the sponsor
• 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), 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.
• 5. Treatment failure of rituximab or interchangeable commercially available biosimilar monotherapy (C-SOT-R or C-HCT) or rituximab plus any concurrent or sequentially administered chemotherapy regimen (C-SOT-R+C) for treatment of PTLD.
• 6. Males and females of any age.
• 7. Eastern Cooperative Oncology Group performance status ≤ 3 for subjects aged ≥ 16 years; Lansky score ≥ 20 for subjects \< 16 years
• 8. For C-HCT 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
• 9. Adequate organ function
• 1. Absolute neutrophil count ≥ 1000/μL, (C-SOT) or ≥ 500/μL (C-HCT), with or without cytokine support
• 2. Platelet count ≥ 50,000/μL, with or without transfusion or cytokine support. For C-HCT, 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)
• 3. 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
• 10. Subject or subject's representative is willing and able to provide written informed consent
• 1. Burkitt lymphoma, classical Hodgkin lymphoma, or any T cell lymphoma
• 2. Daily steroids of \> 0.5 mg/kg prednisone or glucocorticoid equivalent, ongoing methotrexate, or extracorporeal photopheresis
• 3. Untreated CNS PTLD or CNS PTLD for which the subject is actively receiving CNS-directed chemotherapy (systemic or intrathecal) or radiotherapy at enrollment. NOTE:Subjects with previously treated CNS PTLD may enroll if CNS-directed therapy is complete.
• 4. Suspected or confirmed grade ≥ 2 graft-versus-host disease (GvHD) per the Center for International Blood and Marrow Transplant Research consensus grading system at enrollment
• 5. Ongoing or recent use of a checkpoint inhibitor agent (eg, ipilimumab, pembrolizumab, nivolumab) within 3 drug half-lives from the most recent dose to enrollment
• 6. For C-HCT: active adenovirus viremia
• 7. Need for vasopressor or ventilatory support
• 8. Antithymocyte globulin or similar anti-T cell antibody therapy ≤ 4 weeks prior to enrollment
• 9. Treatment with Epstein-Barr virus cytotoxic T lymphocytes or chimeric antigen receptor T cells directed against B cells within 8 weeks of enrollment (C-SOT or C-HCT), or unselected donor lymphocyte infusion within 8 weeks of enrollment (C-HCT only)
• 10. Female who is breastfeeding or pregnant or female of childbearing potential or male with a female partner of childbearing potential unwilling to use a highly effective method of contraception
• 11. Inability to comply with study-related procedures
• 12. Any medical condition or organ system dysfunction that in the investigator\'s opinion, could compromise the participant\'s safety or ability to complete the study