Multicenter, Open Label, Phase 3 Trial of ATA129 for Solid Organ Transplant Subjects With Epstein-Barr Virus-Associated Post-Transplant Lymphoproliferative Disease After Failure of Rituximab or Rituximab and Chemotherapy (ALLELE Study)

This is a multicenter, open-label, single-arm phase 3 trial to assess the efficacy and safety of ATA129 for the treatment of EBV-PTLD in the setting of SOT after failure of rituximab or rituximab plus chemotherapy.

ATA129 cell products will be selected for the subject from a bank of available ATA129 cell products based on matching ≥ 2 HLA alleles, at least one of which is a restricting HLA allele, shared between the ATA129 donor and the subject's EBV-PTLD.

Subjects will be enrolled into one of two cohorts based on therapy prior to enrollment: Cohort A, for those who have failed rituximab alone; and Cohort B, for those who have failed rituximab and have also received chemotherapy for the treatment of PTLD. Study procedures and product administration will be the same for each cohort.

ATA129 will be administered in cycles lasting 5 weeks (35 days). During each cycle, subjects will receive IV ATA129 at a dose of 2×10^6 cells/kg on Days 1, 8, and 15, followed by observation through Day 35.

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 ATA129 cell product
4. Measurable, 18F-deoxyglucose (FDG)-avid (Deauville score ≥ 3) systemic disease (using Lugano Classification response criteria) by positron emission tomography (PET)/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
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
   1. Absolute neutrophil count ≥ 1000/μL, with or without cytokine support
   2. Platelet count ≥ 50,000/μL, with or without transfusion or cytokine support
   3. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin < 3×ULN; however, ALT, AST, and TBILI each ≤ 5×ULN is acceptable if the elevation is considered due to PTLD involvement of the liver.
   4. Creatinine < 3×ULN
9. 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. Previous treatment with EBV-targeted cytotoxic T lymphocytes or chimeric antigen receptor 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 procedures