Epstein-Barr Virus-Associated Post-Transplant Lymphoproliferative Disease MedDRA version: 21.1 Level: PT Classification code 10068349 Term: Epstein-Barr virus associated lymphoproliferative disorder System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 21.0 Level: LLT Classification code 10075146 Term: Post transplant Epstein-Barr virus associated lymphoproliferative disorder System Organ Class: 10029104 - Neoplasms benign, malignant
Conditions
Sponsors
Atara Biotherapeutics, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Prior SOT of kidney, liver, heart, lung, pancreas, small bowel, or any combination of these (SOT cohort); or prior allogeneic HCT (HCT cohort). 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, head diagnostic 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 (SOT subgroup A or HCT cohort) or rituximab plus any concurrent or sequentially administered chemotherapy regimen (SOT subgroup B) for treatment of PTLD. Treatment failure is defined based on rituximab response as follows: a.Radiographic disease progression per Lugano Classification following a minimum cumulative dose of 1125 mg/m2 rituximab (typically, 3 weekly doses of 375 mg/m2), or b. Failure to achieve CR or PR, defined by Lugano radiographic criteria, after a minimum cumulative dose of 1500 mg/m2 rituximab (typically, 4 weekly doses of 375 mg/m2), or c. Relapse/progression of PTLD after a response to rituximab (SOT subgroup A or HCT cohort) or rituximab plus chemotherapy (SOT subgroup B), defined as radiographic and/or biopsy evidence of relapse/progression consistent with PTLD; if the underlying disease for which the subject underwent allogeneic HCT (HCT cohort) was lymphoma, biopsy confirmation of relapsed EBV+ PTLD is required. 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 from birth to 16 years. 8. 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. 9. Adequate organ function: a. Absolute neutrophil count = 1000/µL (SOT cohort) or = 500/µL (HCT cohort), with or without cytokine support b. 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) c. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin (TBILI) each < 5 × the upper limit of normal (ULN); however, ALT, AST, and TBILI each = 10 × ULN 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 (eg, elevated prothrombin time due to liver dysfunction, signs/symptoms of liver dysfunction such as asterixis, or similar). 10. Subject or subject’s representative is willing and able to provide written informed consent. Are the tr
Exclusion criteria
Exclusion criteria: 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 per the Center for International Blood and Marrow Transplant Research (CIBMTR) 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 HCT cohort only: 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 EBV-CTLs or chimeric antigen receptor (CAR) 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). 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: -To determine the clinical benefit of tabelecleucel (ATA129; allogeneic Epstein-Barr virus specific cytotoxic T lymphocytes [EBV-CTLs]) in subjects with EBV-associated post-transplant lymphoproliferative disease (EBV+ PTLD) following (1) solid organ transplant (SOT) and after failure of rituximab (Subgroup A) and rituximab plus chemotherapy (Subgroup B) or (2) allogeneic hematopoietic cell transplant (HCT) after failure of rituximab, as measured by the objective response rate (ORR).;Secondary Objective: - To evaluate duration of response (DOR) in the SOT and HCT cohorts separately - To evaluate ORR and DOR in the SOT and HCT cohorts combined - To evaluate rates of complete response (CR) and partial response (PR) - To evaluate time to response and time to best response - To evaluate overall survival (OS) - To evaluate graft status (SOT subjects only) - To characterize the safety profile of tabelecleucel in this subject population;Primary end point(s): The ORR (CR or PR) obtained following administration of tabelecleucel with up to 2 different HLA restrictions in the SOT or HCT cohort;Timepoint(s) of evaluation of this end point: Monitored throughout the study | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - DOR in SOT and HCT cohorts separately. - ORR and DOR in SOT and HCT cohorts combined. - Rates of CR and PR - Time to response and time to best response - OS - Rates of allograft loss/rejection episodes (for SOT cohort only): loss is defined as allograft removal, resumption of renal replacement therapy (kidney), initiation of a ventricular assist device (heart), need for mechanical ventilation or extracorporeal membrane oxygenation (lung), re-transplant (any), or placement on a SOT list (any); rejection episodes will be defined according to appropriate criteria for the particular organ transplant.;Timepoint(s) of evaluation of this end point: Monitored throughout the study | — |
Countries
Australia, Austria, Belgium, Canada, France, Germany, Italy, Spain, United Kingdom, United States
Contacts
Public ContactLan T Hoang
Atara Biotherapeutics, Inc.
Outcome results
None listed