A Study to Evaluate Tabelecleucel in Participants With Epstein-barr Virus-associated Diseases
Epstein-Barr Virus (EBV)-Associated Diseases, EBV+ Lymphoproliferative Disease With Primary Immunodeficiency (EBV+ PID LPD), EBV+ Lymphoproliferative Disease With Acquired (Non-congenital) Immunodeficiency (EBV+ AID LPD)
About this trial
This is an interventional treatment trial for Epstein-Barr Virus (EBV)-Associated Diseases focused on measuring Allogeneic, Off-The-Shelf T-cell Immunotherapy, Epstein-Barr Virus (EBV), Epstein-Barr Virus-specific Cytotoxic T lymphocyte (EBV-CTL), Solid Organ Transplant (SOT), Hematopoietic Cell Transplant (HCT), EBVision
Eligibility Criteria
Inclusion Criteria:
- Diagnosis of EBV+ disorder
- Eastern Cooperative Oncology Group performance status <= 3 for participants aged >= 16 years; Lansky score >= 20 for participants from 1 year to < 16 years
- Adequate organ function test results, unless organ dysfunction is considered to be due to the underlying EBV-associated disease by the investigator
Cohort-specific Inclusion Criteria:
For participants with PID LPD:
- Newly diagnosed or relapsed/refractory LPD confirmed by biopsy-proven EBV+ LPD or positive cerebrospinal fluid (CSF) cytology with or without radiographically measurable intracranial disease with EBV detected in CSF
- Participant must have systemic measurable disease and/ or CNS measurable disease
- Definitive therapy (eg, allogeneic HCT, gene therapy) for the underlying PID is planned
- Participants with newly diagnosed disease should be ineligible for standard first-line therapy for EBV+ LPD, as determined by the investigator
For participants with AID LPD:
- Newly diagnosed or relapsed/refractory LPD confirmed by biopsy-proven EBV+ LPD or positive CSF cytology, with or without radiographically measurable intracranial disease, with EBV detected in CSF
- Participant must have systemic measurable disease and/ or CNS measurable disease
- Participants who are human immunodeficiency virus positive (HIV+) must meet both of the following criteria: Have an HIV viral load assessed by reverse transcription-polymerase chain reaction (RT-PCR) below the lower limit of detection and CD4 >= 50 cells/μL within 6 months prior to the first dose of tabelecleucel
- Participants with newly diagnosed disease should be ineligible for standard first-line therapy for EBV+ LPD, as determined by the investigator
For participants with CNS PTLD:
- Newly diagnosed or relapsed/refractory EBV+ CNS PTLD histologically confirmed by biopsy-proven EBV+ CNS PTLD or positive CSF cytology with or without radiographically measurable intracranial disease with EBV detected in CSF
- Participant may have systemic and CNS disease or CNS disease only
- Participants with newly diagnosed disease should be ineligible for standard first-line therapy for EBV+ LPD, as determined by the investigator
For participants with EBV+ PTLD, where standard first line therapy (rituximab and/or chemotherapy) is not appropriate, including CD20-negative disease:
- Newly diagnosed, biopsy-proven EBV+ PTLD
- Ineligible for standard first-line therapy for EBV+ PTLD, as determined by the investigator
- Participants must have systemic disease measurable per Lugano Classification criteria, except when contraindicated or mandated by local practice, then MRI may be used.
For participants with sarcoma, including LMS:
- Newly diagnosed or failed systemic first-line therapy for EBV+ sarcoma. Participants with newly diagnosed disease should be ineligible for standard first-line therapy for EBV+ sarcoma, as determined by the investigator.
- Biopsy-proven EBV+ sarcoma
- Measurable disease using diagnostic PET/CT and/or MRI following RECIST 1.1 criteria
For participants with CAEBV:
- Newly diagnosed or previously treated CAEBV
- Detectable EBV viremia on at least 2 occasions at a minimum of 90 days apart
- At least 3 active clinical findings (per Kimura H, et al. Front Immunol. 2017;8:1867) as: Fever >= 38.5°C; splenomegaly, lymphadenopathy, and/or hepatomegaly; cytopenia affecting at least 2 or 3 lineages in the peripheral blood (hemoglobin < 9 g/dL, platelets < 100 × 10^3/mL, neutrophils < 1 × 10^3/mL); hypogammaglobulinemia; hemophagocytosis; hepatitis; neuropathy; rash; and hydroa vacciniforme
For participants with EBV+ viremia with HLH:
- Newly diagnosed or previously treated EBV+ viremia with HLH
- A molecular diagnosis consistent with HLH-2004 trial (per Henter JI, et al. Pediatr Blood Cancer. 2007;48:124-31) OR 5 or more of the clinical symptoms (per Jordan MB, et al. Blood. 2011;118:4041-4052): Fever >= 38.5°C; splenomegaly; cytopenia affecting at least 2 or 3 lineages in the peripheral blood (hemoglobin < 9 g/dL, platelets < 100 × 10^3/mL, neutrophils < 1 × 10^3/mL); hypertriglyceridemia (fasting >= 265 mg/dL) and/or hypofibrinogenemia (<= 150 mg/dL); hemophagocytosis in bone marrow, spleen, lymph nodes, or liver; low or absent natural killer cell (NK-cell) activity; ferritin >= 500 ng/mL; and elevated soluble CD25
Exclusion Criteria:
- Burkitt, T-cell (except in the setting of HLH), natural killer/T-cell lymphoma/LPD, Hodgkin, or transformed lymphoma
- Serious known active infections, defined as ongoing uncontrolled adenovirus infection or infections requiring systemic therapy at the time of enrollment
- Suspected or confirmed Grade >= 2 acute graft-versus-host disease (GvHD) per the Center for International Blood and Marrow Transplant Research (CIBMTR) consensus grading system or extensive chronic GvHD per National Institutes of Health (NIH) consensus criteria at the time of the enrollment
- Need for vasopressor or ventilatory support
Prior therapy (in order of increasing washout period) prior to enrollment as:
- Within 4 weeks or 5 half-lives (whichever is shorter) for any investigational product and/ or any chemotherapy (systemic or intrathecal), targeted small molecule therapy, or antibody/biologic therapy. Note: prior anti-CD20 antibody use is permitted within the washout period if a subsequent disease response assessment indicates disease progression
- Within <= 8 weeks for cellular therapies (EBV-CTLs, chimeric antigen receptor therapies directed at T cells or T-cell subsets, donor lymphocyte infusion, other CTLs); and/or therapies which could impact tabelecleucel function (anti-thymocyte globulin, alemtuzumab)
- Unwilling to use protocol specified contraceptive methods
- Women who are pregnant or breastfeeding
- Ongoing need for daily steroids of > 0.5 mg/kg prednisone or glucocorticoid equivalent, ongoing methotrexate, or extracorporeal photopheresis (protocol-specified dexamethasone is permitted and concludes by the time of enrollment)
- For participants with PID LPD or AID LPD: history of prior allogeneic HCT or solid organ transplant
Sites / Locations
- University of California Los Angeles (UCLA) (Adults and Pediatrics)Recruiting
- Children's Hospital of Orange County (Pediatrics [up to 25 years old])Recruiting
- Lucile Packard Children's Hospital Stanford (Pediatrics only)Recruiting
- University of California Davis Comprehensive Cancer Center (Adults and Pediatrics)Recruiting
- Sylvester Comprehensive Cancer Center/ University of MiamiRecruiting
- Moffit Cancer Center (Adults only)
- Children's Healthcare of Atlanta (Pediatrics only [up to 25 years old])Recruiting
- Emory University/Winship Cancer Institute (Adults [>= 16 years])
- Ann & Robert H. Lurie Children's Hospital of Chicago (Pediatrics only)Recruiting
- University of Maryland Medical Center (Adults only)Recruiting
- Dana Farber Cancer Institute (DFCI) (Adults and Pediatrics)Recruiting
- University of Michigan Rogel Cancer Center (Adults and Pediatrics)Recruiting
- University of Minnesota (Adults only)Recruiting
- Washington University in St. Louis (Adults only)Recruiting
- The Children's Hospital at Montefiore (Adults and Pediatrics)Recruiting
- Columbia University Irving Medical Center (Adults only)
- Memorial Sloan-Kettering Cancer Center (Adults and Pediatrics)Recruiting
- Cleveland Clinic Taussig Cancer Center (Adults and Pediatrics)
- The Ohio State University - The James Cancer Hospital and Solove Research Institute (Adults only)Recruiting
- Oregon Health and Science University (Adults and Pediatrics)Recruiting
- Medical University of South Carolina (Adults and Pediatrics)Recruiting
- University of Texas Southwestern Medical Center (Pediatrics only)Recruiting
- MD Anderson (Adults and Pediatrics)Recruiting
- Medizinische Universität Graz (Adults only)Recruiting
- Uniklinikum Salzburg Landeskrankenhaus (Adults only)Recruiting
- Medizinische Universität Wien (Adults only)Recruiting
- Hôpital Universitaire des Enfants Reine Fabiola (Pediatrics only)Recruiting
- Algemeen Ziekenhuis Sint-Jan Brugge-Oostende - Campus Sint-Jan (Adults only)Recruiting
- Algemeen Ziekenhuis Delta - Campus Rumbeke (Adults only)Recruiting
- Hôpital Saint-Eloi (Adults and Pediatrics)Recruiting
- Hôpital Universitaire Pitié Salpêtrière (Adults only)Recruiting
- Hôpital Necker-Enfants Malades (Adults and Pediatrics)Recruiting
- Azienda Ospedaliero-Universitaria Pisana (Adults only)Recruiting
- Ospedale Pediatrico Bambino Gesù (Adults and Pediatrics)Recruiting
- Ospedale Infantile Regina Margherita (Pediatrics only)Recruiting
- Hospital Universitari Vall d'Hebrón (Adults and Pediatrics)Recruiting
- Hospital Universitario Ramón y Cajal (Adults only)Recruiting
- Hospital Universitario Viegen del Rocio (Adults and Pediatrics)Recruiting
- University Hospital Birmingham NHS Foundation Trust (Adults only)Recruiting
- Great Ormond Street Hospital (Pediatrics only)Recruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Experimental
Experimental
Experimental
Experimental
Experimental
EBV+ PID LPD
EBV+ AID LPD
EBV+ CNS PTLD
EBV+ PTLD (inappropriate for first-line therapy or CD20-negative)
EBV+ sarcoma, including LMS, or smooth muscle tumors
Participants with R/R or newly diagnosed EBV+ PID LPD for whom standard first-line therapy is inappropriate, will receive IV tabelecleucel.
Participants with R/R or newly diagnosed EBV+ AID LPD for whom standard first-line therapy is inappropriate, will receive IV tabelecleucel.
Participants with R/R or newly diagnosed EBV+ CNS PTLD for whom standard first-line therapy is inappropriate, will receive IV tabelecleucel.
Participants with EBV+ PTLD for whom standard first-line therapy (rituximab or chemotherapy) is inappropriate, including CD20-negative disease, will receive IV tabelecleucel.
Participants with newly diagnosed EBV+ sarcoma for whom the standard first-line therapy is inappropriate, including LMS or smooth muscle tumor, will receive IV tabelecleucel.