A Study to Evaluate Tabelecleucel in Participants With Epstein Barr Virus (EBV) Associated Diseases

An Open-label, Single-arm, Multicohort, Phase 2 Study to Assess the Efficacy and Safety of Tabelecleucel in Subjects With Epstein Barr Virus Associated Diseases (EBVision)

The purpose of this study is to assess the efficacy and safety of tabelecleucel in participants with EBV-associated diseases.

Study Overview

• Status: Active, not recruiting
• Conditions: Lymphoproliferative Disorders; Leiomyosarcoma; Stem Cell Transplant Complications; Solid Organ Transplant Complications; Epstein-Barr Virus (EBV)-Associated Diseases; EBV+ Post-transplant Lymphoproliferative Disease (EBV+ PTLD); Allogeneic Hematopoietic Cell Transplant; EBV+ Sarcomas; EBV+ Lymphoproliferative Disease With Primary Immunodeficiency (EBV+ PID LPD); EBV+ Lymphoproliferative Disease With Acquired (Non-congenital) Immunodeficiency (EBV+ AID LPD); EBV+ Posttransplant Lymphoproliferative Disease in Central Nervous System (EBV+ CNS PTLD)
• Intervention / Treatment: Biological: Tabelecleucel

Detailed Description

This is a multicenter, multicohort, open-label, single-arm, Phase 2 study to assess the efficacy and safety of tabelecleucel for the treatment of EBV-associated diseases. Participants will be enrolled in one of the following cohorts:

• EBV+ lymphoproliferative disease (LPD) in the setting of primary immunodeficiency (PID) (EBV+ PID LPD) that is relapsed and/or refractory (R/R) or newly diagnosed where standard first-line therapy is inappropriate
• EBV+ LPD in the setting of acquired (non-congenital) immunodeficiency (AID) (EBV+ AID LPD) that is R/R or newly diagnosed where standard first-line therapy is inappropriate [cohort closed for enrollment after completion of stage1]
• EBV+ post-transplant lymphoproliferative disease (PTLD) involving the central nervous system (CNS) (EBV+ CNS PTLD) that is R/R or newly diagnosed where standard first-line therapy is inappropriate
• EBV+ PTLD where standard first-line therapy (rituximab or chemotherapy) is inappropriate, including cluster of differentiation antigen 20 (CD20)-negative disease
• EBV+ sarcomas, including leiomyosarcoma (LMS), or smooth muscle tumors that is rapidly progressive where standard first-line therapy is inappropriate

Tabelecleucel will be administered in cycles lasting for 35 days. During each cycle, participants will receive tabelecleucel at a dose of 2 x 10^6 cells/kg intravenously (IV) weekly for 3 weeks, followed by observation through Day 35. Treatment will continue until maximal response, disease progression, unacceptable toxicity, or initiation of nonprotocol therapy for the underlying disease. For EBV+ sarcoma cohort, treatment will continue until disease progression, unacceptable toxicity, two consecutive complete responses (CRs), or up to 12 months from the first dose. Participants who fail to respond to initial tabelecleucel treatment may continue tabelecleucel with a different human leukocyte antigen (HLA) restriction (termed a Restriction Switch), if available; administration of tabelecleucel with up to four different HLA restrictions is allowed for any participant.

After treatment is completed or discontinued, participants will complete a safety follow-up visit at 30 days after the last dose and then will enter a quarterly follow-up period. Participants without documented disease progression will be assessed every 3 months after the safety follow-up visit for continued evaluation of disease response until the end of study (EOS) visit at which occurs at 12 (± 1) months after Cycle 1 Day 1 for adults, and 24 (± 1) months after Cycle 1 Day 1 for pediatric participants. Participants with disease progression any time prior to the EOS visit will continue to be followed every 3 months for survival status until the EOS visit.

An adaptive 2-stage design will be used for each relevant cohort in this study. For each cohort, 8 evaluable participants will be enrolled in Stage 1. The decision to move to Stage 2 enrollment will be based on an interim analysis of the first 8 evaluable participants in the cohort using investigator's assessment (per defined radiologic, clinical, and/or laboratory response criteria) who receive tabelecleucel and have at least 1 valid postbaseline disease response assessment. The number of participants enrolled in Stage 2 for each cohort will depend on the number of observed responders in Stage 1. Sponsor may decide not to move forward to Stage 2 in any cohort even if the criteria to move forward for that cohort are met. The decision not to move forward may also be based on data from one or other cohorts.

• Study Type: Interventional
• Enrollment (Estimated): 190
• Phase: Phase 2

Contacts and Locations

Study Locations

• Austria
  • State of Salzburg
    • Salzburg, State of Salzburg, Austria, 5020
      • Uniklinikum Salzburg Landeskrankenhaus (Adults only)
  • State of Vienna
    • Vienna, State of Vienna, Austria, 1090
      • Medizinische Universitat Wien (Adults only)
  • Styria
    • Graz, Styria, Austria, 8036
      • Medizinische Universität Graz (Adults only)
• Belgium
  • Brussles
    • Brussels, Brussles, Belgium, 1020
      • Hôpital Universitaire des Enfants Reine Fabiola (Pediatrics only)
  • West-Vlaanderen
    • Bruges, West-Vlaanderen, Belgium, 8000
      • Algemeen Ziekenhuis Sint-Jan Brugge-Oostende - Campus Sint-Jan (Adults only)
    • Roeselare, West-Vlaanderen, Belgium, 8800
      • Algemeen Ziekenhuis Delta - Campus Rumbeke (Adults only)
• France
  • Paris, France, 75013
    • Hôpital Universitaire Pitié Salpêtrière (Adults only)
  • Montpellier
    • Montpellier, Montpellier, France, 34295
      • Hôpital Saint-Eloi (Adults and Pediatrics)
  • Paris
    • Paris, Paris, France, 75015
      • Hôpital Necker-Enfants Malades (Adults and Pediatrics)
• Italy
  • Pisa
    • Pisa, Pisa, Italy, 56126
      • Azienda Ospedaliero-Universitaria Pisana (Adults only)
  • Roma
    • Roma, Roma, Italy, 00165
      • Ospedale Pediatrico Bambino Gesù (Adults and Pediatrics)
  • Torino
    • Torino, Torino, Italy, 10126
      • Ospedale Infantile Regina Margherita (Pediatrics only)
• Spain
  • Barcelona
    • Barcelona, Barcelona, Spain, 08035
      • Hospital Universitari Vall d'Hebrón (Adults and Pediatrics)
  • Madrid
    • Madrid, Madrid, Spain, 28034
      • Hospital Universitario Ramón y Cajal (Adults only)
  • Sevilla
    • Seville, Sevilla, Spain, 41013
      • Hospital Universitario Virgen del Rocio (Adults and Pediatrics)
• United Kingdom
  • England
    • Birmingham, England, United Kingdom, B15 2TH
      • University Hospital Birmingham NHS Foundation Trust (Adults only)
    • London, England, United Kingdom, WC1N 3JH
      • Great Ormond Street Hospital (Pediatrics only)
• United States
  • California
    • Los Angeles, California, United States, 90095
      • University of California Los Angeles (UCLA) (Adults and Pediatrics)
    • Orange, California, United States, 92868
      • Children's Hospital of Orange County (Pediatrics [up to 25 years old])
    • Palo Alto, California, United States, 94304
      • Lucile Packard Children's Hospital Stanford (Pediatrics only)
    • Sacramento, California, United States, 95817
      • University of California Davis Comprehensive Cancer Center (Adults and Pediatrics)
  • Florida
    • Miami, Florida, United States, 33136
      • Sylvester Comprehensive Cancer Center/ University of Miami
    • Tampa, Florida, United States, 33612
      • Moffit Cancer Center (Adults only)
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Children's Healthcare of Atlanta (Pediatrics only [up to 25 years old])
    • Atlanta, Georgia, United States, 30322
      • Emory University/Winship Cancer Institute (Adults [>= 16 years])
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Ann & Robert H. Lurie Children's Hospital of Chicago (Pediatrics only)
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland Medical Center (Adults only)
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana Farber Cancer Institute (DFCI) (Adults and Pediatrics)
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan Rogel Cancer Center (Adults and Pediatrics)
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota (Adults only)
  • Missouri
    • St Louis, Missouri, United States, 63108
      • Washington University in St. Louis (Adults only)
  • New York
    • New York, New York, United States, 10032
      • Columbia University Irving Medical Center (Adults only)
    • New York, New York, United States, 10065
      • Memorial Sloan-Kettering Cancer Center (Adults and Pediatrics)
    • The Bronx, New York, United States, 10467
      • The Children's Hospital at Montefiore (Adults and Pediatrics)
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Taussig Cancer Center (Adults and Pediatrics)
    • Columbus, Ohio, United States, 43210
      • The Ohio State University - The James Cancer Hospital and Solove Research Institute (Adults only)
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health and Science University (Adults and Pediatrics)
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina (Adults and Pediatrics)
  • Texas
    • Dallas, Texas, United States, 75390
      • University of Texas Southwestern Medical Center (Pediatrics only)
    • Houston, Texas, United States, 77030
      • MD Anderson (Adults and Pediatrics)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Diagnosis of EBV+ disease.
• 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 CNS PTLD:

  • R/R or newly diagnosed EBV+ CNS PTLD for whom the standard. first-line therapy is inappropriate, as determined by the investigator. The CNS PTLD is histologically confirmed by at least biopsy-proven EBV+ CNS PTLD or positive CSF cytology with or without radiographically measurable intracranial disease with EBV detected in CSF.
  • Participants with R/R disease must have had at least one prior line of systemic therapy and one of the following: radiographic disease progression per Lugano Classification during or after treatment or failure to achieve a CR or PR (defined by Lugano radiographic criteria) after standard first-line therapy.
  • Participant may have systemic and CNS disease or CNS disease only.

Exclusion Criteria:

• Currently active Burkitt, T-cell, natural killer/T-cell lymphoma/LPD, Hodgkin, plasmablastic, transformed lymphoma, active hemophagocytic lymphohistiocytosis, or other malignancies requiring systemic therapy.
• Serious known active infections, defined as ongoing uncontrolled adenovirus infection or infections requiring systemic therapy at the time of enrollment, or known history of human immunodeficiency virus (HIV) infection.
• 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 at the time of enrollment.

• Prior therapy (in order of increasing washout period) prior to enrollment as follows:

  • 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: prior tabelecleucel (> 8 weeks prior to enrollment) is permitted if response was obtained or if usual protocol-directed therapeutic options were not exhausted, for cellular therapies (chimeric antigen receptor therapies directed at T-cells or T-cell subsets, donor lymphocyte infusion, other CTLs or virus-specific T-cells); and/or therapies which could impact tabelecleucel function (anti-thymocyte globulin, alemtuzumab).
  • Any prior treatment with EBV-CTLs with the exception of tabelecleucel as above
• Women who are breastfeeding or pregnant.
• Unwilling to comply with protocol specified contraceptive/reproductive restrictions from enrollment through 90 days after the last treatment.
• Inability or unwillingness to comply with all study procedures.
• Ongoing need for daily steroids of > 0.5 mg/kg prednisone or glucocorticoid equivalent, ongoing methotrexate, or extracorporeal photopheresis (for participants with CNS disease, protocol-specified dexamethasone is permitted and concludes by the time of enrollment).
• Any conditions that may put the study outcomes at undue risk (life expectancy < 60 days or any life-threatening illness, medical condition, or organ system dysfunction).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: EBV+ PID LPD; Participants with R/R or newly diagnosed EBV+ PID LPD for whom standard first-line therapy is inappropriate, will receive IV tabelecleucel.	Biological: Tabelecleucel; Tabelecleucel is being investigated as an off-the-shelf, allogeneic T-cell immunotherapy for the treatment of EBV+ malignancies and diseases.; Other Names: EBV-CTLs; ATA129
Experimental: EBV+ CNS PTLD; Participants with R/R or newly diagnosed EBV+ CNS PTLD for whom standard first-line therapy is inappropriate, will receive IV tabelecleucel.	Biological: Tabelecleucel; Tabelecleucel is being investigated as an off-the-shelf, allogeneic T-cell immunotherapy for the treatment of EBV+ malignancies and diseases.; Other Names: EBV-CTLs; ATA129
Experimental: EBV+ sarcoma, including LMS, or smooth muscle tumors; 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.	Biological: Tabelecleucel; Tabelecleucel is being investigated as an off-the-shelf, allogeneic T-cell immunotherapy for the treatment of EBV+ malignancies and diseases.; Other Names: EBV-CTLs; ATA129
Experimental: EBV+ 1L PTLD (inappropriate for first-line therapy or CD20-negative); Participants with EBV+ PTLD for whom standard first-line therapy (rituximab or chemotherapy) is inappropriate, including CD20-negative disease, will receive IV tabelecleucel.	Biological: Tabelecleucel; Tabelecleucel is being investigated as an off-the-shelf, allogeneic T-cell immunotherapy for the treatment of EBV+ malignancies and diseases.; Other Names: EBV-CTLs; ATA129
Experimental: EBV+ AID LPD; Participants with R/R or newly diagnosed EBV+ AID LPD for whom standard first-line therapy is inappropriate, will receive IV tabelecleucel. Cohort closed for enrollment after completion of stage1	Biological: Tabelecleucel; Tabelecleucel is being investigated as an off-the-shelf, allogeneic T-cell immunotherapy for the treatment of EBV+ malignancies and diseases.; Other Names: EBV-CTLs; ATA129

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Objective response rate (ORR)	Up to 2 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Overall survival (OS)	Up to 2 years
Progression-free survival (PFS)	Up to 2 years
Duration of response (DOR)	Up to 2 years
For EBV+ PID LPD cohort: Number of participants who reach definitive therapy (ie, allogeneic HCT) for the underlying disease	Up to 2 years
For EBV+ PID LPD cohort: Time to definitive therapy	Up to 2 years
For EBV+ sarcoma cohort, including LMS, or smooth muscle tumors: Clinical benefit rate	Up to 2 years
For EBV+ sarcoma cohort, including LMS, or smooth muscle tumors: ORR by immune Response Evaluation Criteria in Solid Tumors (iRECIST) criteria	Up to 2 years
Number of Participants who Experience Adverse Events (AE)	Up to 2 years

Collaborators and Investigators

• Sponsor: Pierre Fabre Medicament
• Investigators: Study Director: Glen Lew, Pierre Fabre Laboratories; Study Director: Federica Cattaneo, Pierre Fabre Laboratories

Study record dates

Study Major Dates

• Study Start (Actual): July 14, 2021
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): May 1, 2028

Study Registration Dates

• First Submitted: September 14, 2020
• First Submitted That Met QC Criteria: September 14, 2020
• First Posted (Actual): September 18, 2020

Study Record Updates

• Last Update Posted (Actual): April 27, 2026
• Last Update Submitted That Met QC Criteria: April 22, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Hematopoietic Cell Transplant (HCT); Epstein-Barr Virus (EBV); Allogeneic, Off-The-Shelf T-cell Immunotherapy; Epstein-Barr Virus-specific Cytotoxic T lymphocyte (EBV-CTL); Solid Organ Transplant (SOT); EBVision
• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Infections; Virus Diseases; Neoplasms by Histologic Type; DNA Virus Infections; Lymphatic Diseases; Immunoproliferative Disorders; Sarcoma; Neoplasms, Connective and Soft Tissue; Herpesviridae Infections; Tumor Virus Infections; Neoplasms, Muscle Tissue; Hemic and Lymphatic Diseases; Leiomyosarcoma; Immunologic Deficiency Syndromes; Lymphoproliferative Disorders; Epstein-Barr Virus Infections
• Other Study ID Numbers: ATA129-EBV-205/F60085DL205; 2024-516623-14-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No