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
- 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 monotherapy (SOT cohort, subgroup A or HCT cohort) or rituximab plus chemotherapy (SOT cohort, 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
- Burkitt lymphoma, classical Hodgkin lymphoma, or any T cell lymphoma
- Daily steroids of > 0.5 mg/kg prednisone or glucocorticoid equivalent, ongoing methotrexate, or extracorporeal photopheresis
- 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.
- 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
- 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
- For HCT cohort: active adenovirus viremia
- Need for vasopressor or ventilatory support
- Antithymocyte globulin or similar anti-T cell antibody therapy ≤ 4 weeks prior to enrollment
- Treatment with Epstein-Barr virus cytotoxic T lymphocytes or chimeric antigen receptor T cells directed against B cells within 8 weeks of enrollment (SOT or HCT cohorts), or unselected donor lymphocyte infusion within 8 weeks of enrollment (HCT cohort only)
- 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
- Inability to comply with study-related procedures
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
NOTE, 29 April 2020: Enrollment is temporarily paused at study site/locations with status
"active, not recruiting" due to COVID-19 restrictions.
Trial Phase Phase III
Trial Type Treatment
- Primary ID ATA129-EBV-302
- Secondary IDs NCI-2018-00043
- Clinicaltrials.gov ID NCT03394365