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

Last updated: April 16, 2025
Sponsor: Atara Biotherapeutics
Overall Status: Active - Recruiting

Phase

3

Condition

Lymphoproliferative Disorders

Allo-hematopoietic Stem Cell Transplant

Treatment

tabelecleucel

Clinical Study ID

NCT03394365
ATA129-EBV-302
  • All Genders

Study 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.

Eligibility Criteria

Inclusion

Inclusion Criteria:

  1. Prior SOT of kidney, liver, heart, lung, pancreas, small bowel, or any combinationof these (C-SOT); or prior allogeneic HCT (C-HCT)

  2. A diagnosis of locally assessed, biopsy-proven EBV+ PTLD

  3. Availability of appropriate partially HLA-matched and restricted tabelecleucel hasbeen confirmed by the sponsor

  4. Measurable, 18F-deoxyglucose (FDG)-avid (Deauville score ≥ 3) systemic disease usingLugano Classification response criteria by positron emission tomography (PET)-diagnostic computed tomography (CT), except when contraindicated or mandatedby local practice, then magnetic resonance imaging (MRI) may be used. For subjectswith treated central nervous system (CNS) disease, a head CT and/or brain/spinal MRIas clinically appropriate will be required to follow CNS disease response per LuganoClassification response criteria.

  5. Treatment failure of rituximab or interchangeable commercially available biosimilarmonotherapy (C-SOT-R or C-HCT) or rituximab plus any concurrent or sequentiallyadministered chemotherapy regimen (C-SOT-R+C) for treatment of PTLD.

  6. Males and females of any age.

  7. Eastern Cooperative Oncology Group performance status ≤ 3 for subjects aged ≥ 16years; Lansky score ≥ 20 for subjects < 16 years

  8. For C-HCT only: If allogeneic HCT was performed as treatment for an acute lymphoidor myeloid malignancy, the underlying primary disease for which the subjectunderwent transplant must be in morphologic remission

  9. Adequate organ function

  10. Absolute neutrophil count ≥ 1000/μL, (C-SOT) or ≥ 500/μL (C-HCT), with orwithout cytokine support

  11. 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 withouttransfusion support, is permissible if the subject has not had grade ≥ 2bleeding in the prior 4 weeks (where grading of the bleeding is determined perthe National Cancer Institute's Common Terminology Criteria for Adverse Events [CTCAE], version 5.0)

  12. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and totalbilirubin each < 5 × the upper limit of normal; however, ALT, AST, andtotal bilirubin each ≤ 10 × upper limit of normal is acceptable if theelevation is considered by the investigator to be due to EBV and/or PTLDinvolvement of the liver as long as there is no known evidence of significantliver dysfunction

  13. Subject or subject's representative is willing and able to provide written informedconsent

Exclusion

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 receivingCNS-directed chemotherapy (systemic or intrathecal) or radiotherapy at enrollment.NOTE:Subjects with previously treated CNS PTLD may enroll if CNS-directed therapy iscomplete.

  4. Suspected or confirmed grade ≥ 2 graft-versus-host disease (GvHD) per the Center forInternational Blood and Marrow Transplant Research consensus grading system atenrollment

  5. Ongoing or recent use of a checkpoint inhibitor agent (eg, ipilimumab,pembrolizumab, nivolumab) within 3 drug half-lives from the most recent dose toenrollment

  6. For C-HCT: active adenovirus viremia

  7. Need for vasopressor or ventilatory support

  8. Antithymocyte globulin or similar anti-T cell antibody therapy ≤ 4 weeks prior toenrollment

  9. Treatment with Epstein-Barr virus cytotoxic T lymphocytes or chimeric antigenreceptor T cells directed against B cells within 8 weeks of enrollment (C-SOT orC-HCT), or unselected donor lymphocyte infusion within 8 weeks of enrollment (C-HCTonly)

  10. Female who is breastfeeding or pregnant or female of childbearing potential or malewith a female partner of childbearing potential unwilling to use a highly effectivemethod of contraception

  11. Inability to comply with study-related procedures

  12. Any medical condition or organ system dysfunction that in the investigator'sopinion, could compromise the participant's safety or ability to completethe study

Study Design

Total Participants: 66
Treatment Group(s): 1
Primary Treatment: tabelecleucel
Phase: 3
Study Start date:
December 29, 2017
Estimated Completion Date:
June 30, 2027

Study Description

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-R and SOT-R+C (Cohort [C]-SOT) or HCT after failure of rituximab (C-HCT).

SOT-R further included participants:

  1. who did not receive chemotherapy and did not have a documented medical reason not to receive chemotherapy (SOT-Ro) or

  2. who were considered chemotherapy ineligible/inappropriate (SOT-R-Ci)

Combined population (SOT-R-Ci, SOT-R+C, and HCT) and (SOT-R-Ci and SOT-R+C) who received commercial product, or a product manufactured using a comparable process version (PV) were also used for analysis of outcomes.

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 (C-SOT) or up to 4 different HLA restrictions (C-HCT). The study includes a total of 5 years of follow-up for disease and survival status.

Connect with a study center

  • The Children's Hospital at Westmead (Pediatrics only)

    Westmead, New South Wales 2145
    Australia

    Active - Recruiting

  • Westmead Hospital (Adults only)

    Westmead, New South Wales 2145
    Australia

    Active - Recruiting

  • The Prince Charles Hospital (Adults only)

    Chermside, Queensland 4032
    Australia

    Active - Recruiting

  • Royal Adelaide Hospital (Adults only)

    Adelaide, South Australia 5000
    Australia

    Active - Recruiting

  • The Royal Children's Hospital Melbourne (Pediatrics only)

    Melbourne, Victoria 3052
    Australia

    Active - Recruiting

  • Fiona Stanley Hospital (Adults only)

    Murdoch, Western Australia 6150
    Australia

    Active - Recruiting

  • Medizinische Universitat Wien (Adults only)

    Wien, 1090
    Austria

    Active - Recruiting

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

    Liège, Brussels 4000
    Belgium

    Active - Recruiting

  • Universitair Ziekenhuis Leuven (Adults and Pediatrics)

    Leuven, Flemish Brabant 3000
    Belgium

    Active - Recruiting

  • Alberta Children's Hospital (Adults and Pediatrics)

    Calgary, Alberta T3B 6A8
    Canada

    Active - Recruiting

  • Princess Margaret Cancer Centre (Adults only)

    Toronto, Ontario M5G 2M9
    Canada

    Active - Recruiting

  • Sick Kids (Pediatrics only)

    Toronto, Ontario M5G 1X8
    Canada

    Active - Recruiting

  • Centre Hospitalier Universitaire de Bordeaux (Adults only)

    Pessac, Aquitaine 33600
    France

    Active - Recruiting

  • Groupe Hospitalier du Haut Leveque (Adults only)

    Pessac, Aquitaine 33600
    France

    Active - Recruiting

  • Hôpital Saint Antoine (Adults only)

    Paris, Ile-de-France 75571
    France

    Active - Recruiting

  • Centre Hospitalier Régional Universitaire de Lille (Adults and Pediatrics)

    Lille cedex, Nord-Pas-de-Calais 59037
    France

    Active - Recruiting

  • Hôpital Necker-Enfants Malades (Pediatrics only)

    Paris 15, Île-de-France 75015
    France

    Active - Recruiting

  • Hôpital Universitaire Pitié Salpêtrière (Adults only)

    Paris Cedex 13, Île-de-France 75651
    France

    Active - Recruiting

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

    Milano, 20162
    Italy

    Active - Recruiting

  • Fondazione IRCCS Policlinico San Matteo (Adults and Pediatrics)

    Pavia, 27100
    Italy

    Active - Recruiting

  • Fondazione Policlinico Universitario Agostino Gemelli (Adults only)

    Roma, 00168
    Italy

    Active - Recruiting

  • Ospedale Pediatrico Bambino Gesu (Pediatrics only)

    Roma, 165
    Italy

    Active - Recruiting

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

    Torino, 10126
    Italy

    Active - Recruiting

  • Hospital Duran i Reynals

    Badalona, Barcelona 8908
    Spain

    Active - Recruiting

  • Hospital Duran i Reynals (Adults and Pediatrics)

    Badalona, Barcelona 8908
    Spain

    Active - Recruiting

  • Hospital Universitario Marqués de Valdecilla (Adults and Pediatrics)

    Santander, Cantabria 39008
    Spain

    Active - Recruiting

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

    Barcelona, 08035
    Spain

    Active - Recruiting

  • Hospital General Universitario Gregorio Marañón (Adults and Pediatrics)

    Madrid, 28009
    Spain

    Active - Recruiting

  • University Hospital Virgen del Rocio (Adults and Pediatrics)

    Sevilla, 41013
    Spain

    Active - Recruiting

  • Hospital Universitario La Fe (Adults and Pediatrics)

    Valencia, 46009
    Spain

    Active - Recruiting

  • University Hospitals Birmingham NHS Foundation Trust (Adults only)

    Birmingham, England B15 2GW
    United Kingdom

    Active - Recruiting

  • Imperial College Healthcare NHS Trust (Adults only)

    London, England W12 0HS
    United Kingdom

    Active - Recruiting

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

    London, England SE5 9RS
    United Kingdom

    Completed

  • 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 Cancer Center (Adults only)

    Loma Linda, California 92354
    United States

    Active - Recruiting

  • Loma Linda University Medical Center (Adults only)

    Loma Linda, California 92354
    United States

    Site Not Available

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

    Los Angeles, California 90027
    United States

    Site Not Available

  • 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, District of Columbia 20007
    United States

    Site Not Available

  • 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

    Site Not Available

  • Arthur M. Blank Hospital (Pediatrics)

    Atlanta, Georgia 30329
    United States

    Site Not Available

  • Children's Healthcare of Atlanta at Egleston (Pediatrics)

    Atlanta, Georgia 30322-1060
    United States

    Active - Recruiting

  • Winship Cancer Institute (Adults only)

    Atlanta, Georgia 30322
    United States

    Completed

  • Winship Cancer Institute of Emory University (Adults only)

    Atlanta, Georgia 30322
    United States

    Active - Recruiting

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

    Chicago, Illinois 60611
    United States

    Site Not Available

  • 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

    Site Not Available

  • 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

    Site Not Available

  • Washington University School of Medicine (Adults only)

    Saint Louis, Missouri 63110
    United States

    Site Not Available

  • Montefiore Medical Center (Adults only)

    Bronx, New York 10467
    United States

    Completed

  • Montefiore Medical Center (Pediatrics only)

    Bronx, New York 10467
    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

    Site Not Available

  • Weill Cornell Medicine (Adults only)

    New York, New York 10021
    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

    Site Not Available

  • Duke Cancer Institute (Adults only)

    Durham, North Carolina 27710
    United States

    Site Not Available

  • Cleveland Clinic Foundation (Adults and Pediatrics)

    Cleveland, Ohio 44195
    United States

    Site Not Available

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

    Columbus, Ohio 43210
    United States

    Site Not Available

  • Nationwide Children's Hospital (Pediatrics only)

    Columbus, Ohio 43205
    United States

    Completed

  • The Ohio State University - Arthur G. James Cancer Center Hospital (Adults and Pediatrics)

    Columbus, Ohio 43210
    United States

    Active - Recruiting

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

    Portland, Oregon 97239
    United States

    Site Not Available

  • Children's Hospital of Philadelphia (Pediatrics only)

    Philadelphia, Pennsylvania 19104
    United States

    Active - Recruiting

  • Hospital of the University of Pennsylvania (Adults only)

    Philadelphia, Pennsylvania 19104
    United States

    Site Not Available

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

    Philadelphia, Pennsylvania 19104
    United States

    Site Not Available

  • University of Pennsylvania (Adults only)

    Philadelphia, Pennsylvania 19104
    United States

    Site Not Available

  • 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

    Site Not Available

  • 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

    Site Not Available

  • Baylor Scott and White Research Institute (Adults only)

    Dallas, Texas 75246
    United States

    Site Not Available

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

    Dallas, Texas 75390
    United States

    Site Not Available

  • MD Anderson Cancer Center (Adults and Pediatrics)

    Houston, Texas 77030
    United States

    Active - Recruiting

  • MD Anderson Cancer Center (Pediatrics and Adult)

    Houston, Texas 77030
    United States

    Site Not Available

  • Froedtert Hospital & the Medical College of Wisconsin (Adults only)

    Milwaukee, Wisconsin 53226
    United States

    Completed

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

    Milwaukee, Wisconsin 53226
    United States

    Completed

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