A Phase 3 Study of Tabelecleucel for Participants With Epstein-Barr Virus-Associated Post-Transplant Lymphoproliferative Disease After Failure With Rituximab or Rituximab and Chemotherapy

NCT03394365 | Recruiting Phase 3 FDA Drug

• 2 other identifiers: ATA129-EBV-302/F60085DL3022024-516622-57-00
• Study Type: interventional
• Target: 115
• Locations: 8 countries
• Sites: 65

Brief Summary

The purpose of this study is to determine the clinical benefit and characterize the safety profile of tabelecleucel for the treatment of Epstein-Barr virus-associated post-transplant lymphoproliferative disease (EBV+ PTLD) in the setting of (1) solid organ transplant (SOT) after failure of rituximab (SOT-R) and rituximab plus chemotherapy (SOT-R+C) or (2) allogeneic hematopoietic cell transplant (HCT) after failure of rituximab.

Conditions

Epstein-Barr Virus+ Associated Post-transplant Lymphoproliferative Disease (EBV+ PTLD); Solid Organ Transplant Complications; Lymphoproliferative Disorders; Allogeneic Hematopoietic Cell Transplant; Stem Cell Transplant Complications

Keywords

Epstein-Barr Virus (EBV)-associated Lymphoproliferative Disease (LPD); Epstein-Barr Virus (EBV); Cytotoxic T lymphocyte (CTL); Cancer After Transplant; Kidney transplant; Renal transplant; Liver transplant; Heart transplant; Lung transplant; Intestinal transplant; Pancreas transplant; Post-transplant Lymphoma; Solid Organ Transplant (SOT); Bone Marrow Transplant Complications; Epstein-Barr Virus-specific Cytotoxic T Lymphocytes (EBV-CTL); Hematopoietic Cell Transplant (HCT); Hematopoietic Stem Cell Transplantation (HSCT); Allogeneic Hematopoietic Cell Transplant; Allogeneic, Off-The-Shelf T-cell Immunotherapy

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR) in the Analysis Cohorts C-SOT, C-HCT, and Combined Population (C-SOT-R+C, C-SOT-R-Ci, and C-HCT) Who Received Commercial Product, or a Product Manufactured Using a Comparable PV

  2 years

Secondary Outcomes (9)

• Duration of Response (DOR) in the Analysis Cohorts C-SOT and C-HCT Separately

  2 years

• ORR in the Analysis Cohorts C-SOT and C-HCT Combined

  2 years

• ORR and DOR in Participants who Received Commercial Product or a Product Manufactured Using a Comparable PV in the Analysis Cohorts C-SOT-R-Ci and C-SOT-R+C Separately and Combined, and in the Analysis Cohort C-HCT

  2 years

• DOR in a Combined Population (SOT-R-Ci, SOT-R+C, and HCT) who Received Commercial Product or a Product Manufactured Using a Comparable PV

  2 years

• Rates of Complete Response (CR) and Partial Response (PR)

  2 years

Study Arms (3)

Cohort SOT-R (C-SOT-R)

EXPERIMENTAL

Participants with EBV+ PTLD following SOT that has failed rituximab will receive IV tabelecleucel.

Biological: tabelecleucel

Cohort SOT-R+C (C-SOT-R+C)

EXPERIMENTAL

Participants with EBV+ PTLD following SOT that has failed both rituximab and chemotherapy will receive IV tabelecleucel.

Biological: tabelecleucel

Cohort HCT (C-HCT)

EXPERIMENTAL

Participants with EBV+ PTLD following HCT that has failed rituximab containing regimen will receive IV tabelecleucel.

Biological: tabelecleucel

Interventions

tabelecleucel BIOLOGICAL

Tabelecleucel is being investigated as an off-the-shelf, allogeneic T-cell immunotherapy for the treatment of EBV+ malignancies and diseases.

Also known as: tab-cel®, ATA129, EBV-CTL, Ebvallo®

Cohort HCT (C-HCT); Cohort SOT-R (C-SOT-R); Cohort SOT-R+C (C-SOT-R+C)

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Prior SOT of kidney, liver, heart, lung, pancreas, small bowel, or any combination of these (C-SOT); or prior allogeneic HCT (C-HCT).
• 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 participants 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 or interchangeable commercially available biosimilar monotherapy (C-SOT-R or C-HCT) or rituximab plus any concurrent or sequentially administered chemotherapy regimen (C-SOT-R+C) for treatment of PTLD.
• Males and females of any age.
• Eastern Cooperative Oncology Group performance status ≤ 3 for participants aged ≥ 16 years; Lansky score ≥ 20 for participants \< 16 years.
• For C-HCT only: If allogeneic HCT was performed as treatment for an acute lymphoid or myeloid malignancy, the underlying primary disease for which the participant underwent transplant must be in morphologic remission.
• Adequate organ function.
• Absolute neutrophil count ≥ 1000/μL, (C-SOT) or ≥ 500/μL (C-HCT), with or without cytokine support.
• Platelet count ≥ 50,000/μL, with or without transfusion or cytokine support. For C-HCT, platelet count \< 50,000/μL but ≥ 20,000/μL, with or without transfusion support, is permissible if the participant 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.
• Participant or participant's representative is willing and able to provide written informed consent.

You may not qualify if:

• Currently active Burkitt, T-cell, NK/T-cell lymphoma/LPD, Hodgkin, plasmablastic, transformed lymphoma, active hemophagocytic lymphohistiocytosis, or other malignancies requiring systemic therapy.
• 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 participant is actively receiving CNS-directed chemotherapy (systemic or intrathecal) or radiotherapy at enrollment. NOTE: Participants 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 C-HCT: 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 (C-SOT or C-HCT), or unselected donor lymphocyte infusion within 8 weeks of enrollment (C-HCT 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.
• Any medical condition or organ system dysfunction that in the investigator';s opinion, could compromise the participant's safety or ability to complete the study.

Sponsors & Collaborators

• Pierre Fabre Medicament: lead

Study Sites (71)

City of Hope (Adults and Pediatrics)

Duarte, California, 91010, United States

COMPLETED

University of California San Diego Moores Cancer Center (Adults only)

La Jolla, California, 92093, United States

COMPLETED

Loma Linda University Medical Center (Adults only)

Loma Linda, California, 92354, United States

RECRUITING

Children's Hospital Los Angeles, Div. of Research Immunology/BMT (Adults and Pediatrics)

Los Angeles, California, 90027, United States

RECRUITING

UCLA Medical Center (Adults and Pediatrics)

Los Angeles, California, 90095, United States

COMPLETED

University of California Davis Comprehensive Cancer Center (Adults only)

Sacramento, California, 95817, United States

COMPLETED

Yale University (Adults and Pediatrics)

New Haven, Connecticut, 06519, United States

COMPLETED

MedStar Georgetown University Hospital (Adults and Pediatrics)

Washington D.C., District of Columbia, 20007, United States

RECRUITING

University of Florida (Adults and Pediatrics)

Gainesville, Florida, 32610, United States

COMPLETED

University of Miami/Jackson Memorial Hospital (Adults only)

Miami, Florida, 33136, United States

RECRUITING

Winship Cancer Institute (Adults only)

Atlanta, Georgia, 30322, United States

COMPLETED

Arthur M. Blank Hospital (Pediatrics)

Atlanta, Georgia, 30329, United States

RECRUITING

Ann & Robert H. Lurie Children's Hospital of Chicago (Adults and Pediatrics)

Chicago, Illinois, 60611, United States

RECRUITING

University of Chicago Medical Center - Duchossois Center for Advanced Medicine (Adults only)

Chicago, Illinois, 60637, United States

COMPLETED

Loyola University Medical Center (Adults and Pediatrics)

Maywood, Illinois, 60153, United States

RECRUITING

University of Maryland School of Medicine (Adults only)

Baltimore, Maryland, 21201, United States

COMPLETED

Dana Farber Cancer Institute, Brigham and Women's Hospital (Adults and Pediatrics)

Boston, Massachusetts, 02215, United States

RECRUITING

Washington University School of Medicine (Adults only)

St Louis, Missouri, 63110, United States

RECRUITING

Weill Cornell Medicine (Adults only)

New York, New York, 10021, United States

COMPLETED

Columbia University Medical Center (Adults and Pediatrics)

New York, New York, 10032, United States

COMPLETED

Memorial Sloan Kettering Cancer Center (Adults and Pediatrics)

New York, New York, 10065, United States

COMPLETED

Montefiore Medical Center (Adults only)

The Bronx, New York, 10467, United States

COMPLETED

Montefiore Medical Center (Pediatrics only)

The Bronx, New York, 10467, United States

COMPLETED

University of North Carolina at Chapel Hill, Lineberger Comprehensive Cancer Center (Adults and Pediatrics)

Chapel Hill, North Carolina, 27599, United States

COMPLETED

Carolinas Medical Center/Levine Children's Hospital (Adults and Pediatrics)

Charlotte, North Carolina, 28204, United States

RECRUITING

Duke Cancer Institute (Adults and Pediatrics)

Durham, North Carolina, 27710, United States

RECRUITING

Cleveland Clinic Foundation (Adults and Pediatrics)

Cleveland, Ohio, 44195, United States

RECRUITING

Nationwide Children's Hospital (Pediatrics only)

Columbus, Ohio, 43205, United States

COMPLETED

Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (Adults and Pediatrics)

Columbus, Ohio, 43210, United States

RECRUITING

Oregon Health and Science University Physicians Pavilion (Adults and Pediatrics)

Portland, Oregon, 97239, United States

RECRUITING

Hospital of the University of Pennsylvania (Adults only)

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

The Children's Hospital of Philadelphia Oncology Division, Blood & Marrow Transplant Section (Pediatrics)

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

University of Pittsburgh Medical Center (Adults only)

Pittsburgh, Pennsylvania, 15232, United States

COMPLETED

Medical University of South Carolina (Adults and Pediatrics)

Charleston, South Carolina, 29425, United States

ACTIVE NOT RECRUITING

Saint Jude Children's Research Hospital (Pediatrics only)

Memphis, Tennessee, 38105, United States

COMPLETED

Vanderbilt University Medical Center Henry-Joyce Cancer Clinic (Adults and Pediatrics)

Nashville, Tennessee, 37232, United States

RECRUITING

Baylor Scott and White Research Institute (Adults only)

Dallas, Texas, 75246, United States

RECRUITING

University of Texas Southwestern Medical Center - Children's Medical Center (Pediatrics only)

Dallas, Texas, 75390, United States

RECRUITING

MD Anderson Cancer Center (Pediatrics and Adult)

Houston, Texas, 77030, United States

RECRUITING

Froedtert and Medical College of Wisconsin - Clinical Cancer Center (Adults only)

Milwaukee, Wisconsin, 53226, United States

COMPLETED

The Children's Hospital at Westmead (Pediatrics only)

Westmead, New South Wales, 2145, Australia

RECRUITING

Westmead Hospital (Adults only)

Westmead, New South Wales, 2145, Australia

RECRUITING

The Prince Charles Hospital (Adults only)

Chermside, Queensland, 4032, Australia

RECRUITING

Royal Adelaide Hospital (Adults only)

Adelaide, South Australia, 5000, Australia

RECRUITING

The Royal Children's Hospital Melbourne (Pediatrics only)

Melbourne, Victoria, 3052, Australia

RECRUITING

Fiona Stanley Hospital (Adults only)

Murdoch, Western Australia, 6150, Australia

RECRUITING

Medizinische Universitat Wien (Adults only)

Vienna, Austria, 1090, Austria

ACTIVE NOT RECRUITING

Centre Hospitalier Universitaire de Liège Site Sart Tilman (Adults and Pediatrics)

Liège, Brussels Capital, 4000, Belgium

COMPLETED

Universitair Ziekenhuis Leuven (Adults and Pediatrics)

Leuven, Flemish Brabant, 3000, Belgium

ACTIVE NOT RECRUITING

Alberta Children's Hospital (Adults and Pediatrics)

Calgary, Alberta, T3B 6A8, Canada

RECRUITING

Sick Kids (Pediatrics only)

Toronto, Ontario, M5G 1X8, Canada

RECRUITING

Princess Margaret Cancer Centre (Adults only)

Toronto, Ontario, M5G 2M9, Canada

RECRUITING

Centre Hospitalier Universitaire de Bordeaux (Adults only)

Pessac, Aquitaine, 33600, France

COMPLETED

Centre Hospitalier Régional Universitaire de Lille (Adults and Pediatrics)

Lille, Hauts-de-France, 59037, France

COMPLETED

Hôpital Necker-Enfants Malades (Pediatrics only)

Paris, Île-de-France Region, 75015, France

COMPLETED

Hôpital Saint Antoine (Adults only)

Paris, Île-de-France Region, 75571, France

COMPLETED

Hôpital Universitaire Pitié Salpêtrière (Adults only)

Paris, Île-de-France Region, 75651, France

COMPLETED

Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda (Adults only)

Milan, Milano, 20162, Italy

COMPLETED

Fondazione IRCCS Policlinico San Matteo (Adults and Pediatrics)

Pavia, Pavia, 27100, Italy

COMPLETED

Fondazione Policlinico Universitario Agostino Gemelli (Adults only)

Roma, Roma, 00168, Italy

COMPLETED

Ospedale Pediatrico Bambino Gesu (Pediatrics only)

Roma, Roma, 165, Italy

COMPLETED

Azienda Ospedaliera - Universitaria Città della Salute e della Scienza di Torino (Adults only)

Torino, Torino, 10126, Italy

COMPLETED

Hospital Duran i Reynals (Adults and Pediatrics)

Badalona, BARCELONA, 8908, Spain

RECRUITING

Hospital Universitari Vall d'Hebrón - Institut de Recerca (Adults and Pediatrics)

Barcelona, Barcelona, 08035, Spain

SUSPENDED

Hospital Universitario Marqués de Valdecilla (Adults and Pediatrics)

Santander, Cantabria, 39008, Spain

RECRUITING

Hospital General Universitario Gregorio Marañón (Adults and Pediatrics)

Madrid, Madrid, 28009, Spain

RECRUITING

University Hospital Virgen del Rocio (Adults and Pediatrics)

Seville, Spain, 41013, Spain

RECRUITING

Hospital Universitario La Fe (Adults and Pediatrics)

Valencia, Valencia, 46009, Spain

RECRUITING

University Hospitals Birmingham NHS Foundation Trust (Adults only)

Birmingham, England, B15 2GW, United Kingdom

RECRUITING

King's College Hospital NHS Foundation Trust (Adults only)

London, England, SE5 9RS, United Kingdom

COMPLETED

Imperial College Healthcare NHS Trust (Adults only)

London, England, W12 0HS, United Kingdom

RECRUITING

Related Publications (1)

• Mahadeo KM, Baiocchi R, Beitinjaneh A, Chaganti S, Choquet S, Dierickx D, Dinavahi R, Duan X, Gamelin L, Ghobadi A, Guzman-Becerra N, Joshi M, Mehta A, Navarro WH, Nikiforow S, O'Reilly RJ, Reshef R, Ruiz F, Spindler T, Prockop S. Tabelecleucel for allogeneic haematopoietic stem-cell or solid organ transplant recipients with Epstein-Barr virus-positive post-transplant lymphoproliferative disease after failure of rituximab or rituximab and chemotherapy (ALLELE): a phase 3, multicentre, open-label trial. Lancet Oncol. 2024 Mar;25(3):376-387. doi: 10.1016/S1470-2045(23)00649-6. Epub 2024 Jan 31.

  PMID: 38309282 DERIVED

MeSH Terms

Conditions

Lymphoproliferative Disorders; Epstein-Barr Virus Infections

Condition Hierarchy (Ancestors)

Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections

Study Officials

• Anke Friedetzky

  Pierre Fabre Laboratories

  STUDY DIRECTOR

Central Study Contacts

Claire Fabre

CONTACT

6 42 04 84 76; claire.fabre@pierre-fabre.com

Marie Bosredon

CONTACT

7 84 14 59 82; marie.bosredon@pierre-fabre.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 29, 2017
• First Posted: January 9, 2018
• Study Start: December 29, 2017
• Primary Completion (Estimated): May 31, 2030
• Study Completion (Estimated): August 1, 2030
• Last Updated: February 20, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

CA (3); BE (2); ES (6); FR (5); US (40); IT (5); GB (3); AU (1)