Epstein-Barr Virus+ Associated Post-transplant Lymphoproliferative Disease (EBV+ PTLD)Phase 3ALLELENCT03394365
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
A Phase 3 study testing tabelecleucel in people with Epstein-Barr Virus+ Associated Post-transplant Lymphoproliferative Disease (EBV+ PTLD) and Solid Organ Transplant Complications, run by Pierre Fabre Medicament at 71 sites in 9 countries.
Trial 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… Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Epstein-Barr Virus+ Associated Post-transplant Lymphoproliferative Disease (EBV+ PTLD), Solid Organ Transplant Complications, Lymphoproliferative Disorders
- What is being tested?
- tabelecleucel
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 115 participants
- Where
- 71 sitesin 9 countries
- Study dates
- 29 Dec 2017to Aug 2030
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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). Magnetic resonance imaging (MRI) may be used when PET-CT is contraindicated, mandated by local practice, or when disease status cannot be assessed adequately in the investigator's opinion and is confirmed by the Sponsor. For participants with treated CNS disease, a head diagnostic CT and/or brain/spinal MRI as clinically appropriate will be required to follow CNS disease response per Lugano Classification response criteria.
- Treatment failure to CD20-directed antibody, i.e. rituximab or interchangeable commercially available biosimilar monotherapy (SOT-R or HCT cohort) or rituximab plus any concurrent or sequentially administered chemotherapy regimen (SOT-R+C) for treatment of PTLD.
- Males and females of any age.
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- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
71 sites in 9 countries. Contact the study team or a site near you to ask about taking part.
71 sites in 9 countries
United States40 sites, 20 recruiting
- Completed
Winship Cancer Institute (Adults only)
Atlanta, Georgia, 30322
- Recruiting
Arthur M Blank Hospital - Children's Healthcare of Atlanta
Atlanta, Georgia, 30329
Suhag Parikh, MD, 1 (404) 727-8930
- Completed
University of Maryland School of Medicine (Adults only)
Baltimore, Maryland, 21201
- Recruiting
Dana Farber Cancer Institute, Brigham and Women's Hospital (Adults and Pediatrics)
Boston, Massachusetts, 02215
Sarah Nikiforow, MD, 617-632-6640
- Completed
University of North Carolina at Chapel Hill, Lineberger Comprehensive Cancer Center (Adults and Pediatrics)
Chapel Hill, North Carolina, 27599
- Completed
Medical University of South Carolina (Adults and Pediatrics)
Charleston, South Carolina, 29425
- Recruiting
Carolinas Medical Center/Levine Children's Hospital (Adults and Pediatrics)
Charlotte, North Carolina, 28204
Michael Kent, MD, 704-381-9900
- Recruiting
Ann & Robert H. Lurie Children's Hospital of Chicago (Adults and Pediatrics)
Chicago, Illinois, 60611
Sonali Chaudhury, MD, 312-227-4090
- Completed
University of Chicago Medical Center - Duchossois Center for Advanced Medicine (Adults only)
Chicago, Illinois, 60637
- Recruiting
Cleveland Clinic Foundation (Adults and Pediatrics)
Cleveland, Ohio, 44195
Rabi Hanna, MD, 1 (216) 444-0663
- Completed
Nationwide Children's Hospital (Pediatrics only)
Columbus, Ohio, 43205
- Recruiting
Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (Adults and Pediatrics)
Columbus, Ohio, 43210
Robert Baiocchi, MD, PhD, (614) 293-3196
- Recruiting
Baylor Scott and White Research Institute (Adults only)
Dallas, Texas, 75246
Luis Pineiro, MD, 214-370-1000
- Recruiting
University of Texas Southwestern Medical Center - Children's Medical Center (Pediatrics only)
Dallas, Texas, 75390
Tamra Slone, MD, 1 (214) 648-3150
- Completed
City of Hope (Adults and Pediatrics)
Duarte, California, 91010
- Recruiting
Duke Cancer Institute (Adults and Pediatrics)
Durham, North Carolina, 27710
Matthew McKinney, MD, 1 (919) 684-8111
- Completed
University of Florida (Adults and Pediatrics)
Gainesville, Florida, 32610
- Recruiting
MD Anderson Cancer Center (Pediatrics and Adult)
Houston, Texas, 77030
Priti Tewari, MD, 1 713-632-5087
- Completed
University of California San Diego Moores Cancer Center (Adults only)
La Jolla, California, 92093
- Recruiting
Loma Linda University Medical Center (Adults only)
Loma Linda, California, 92354
Aditya Sharma, MD, 1 (909) 558-4910
- Recruiting
Children's Hospital Los Angeles, Div. of Research Immunology/BMT (Adults and Pediatrics)
Los Angeles, California, 90027
Amber Medina, 323-361-5654
Sarah Richman, MD, 323-361-2434
- Completed
UCLA Medical Center (Adults and Pediatrics)
Los Angeles, California, 90095
- Recruiting
Loyola University Medical Center (Adults and Pediatrics)
Maywood, Illinois, 60153
Patrick Hagen, MD, 1 (708) 327-2241
- Completed
Saint Jude Children's Research Hospital (Pediatrics only)
Memphis, Tennessee, 38105
- Recruiting
University of Miami/Jackson Memorial Hospital (Adults only)
Miami, Florida, 33136
Amer Beitinjaneh, MD, MPH, MSc, 1 (305) 243-9848
- Completed
Froedtert and Medical College of Wisconsin - Clinical Cancer Center (Adults only)
Milwaukee, Wisconsin, 53226
- Recruiting
Vanderbilt University Medical Center Henry-Joyce Cancer Clinic (Adults and Pediatrics)
Nashville, Tennessee, 37232
Bhagirathbhai Dholaria, MD, 1 (615) 875-3112
- Completed
Yale University (Adults and Pediatrics)
New Haven, Connecticut, 06519
- Completed
Weill Cornell Medicine (Adults only)
New York, New York, 10021
- Completed
Columbia University Medical Center (Adults and Pediatrics)
New York, New York, 10032
- Completed
Memorial Sloan Kettering Cancer Center (Adults and Pediatrics)
New York, New York, 10065
- Recruiting
Hospital of the University of Pennsylvania (Adults only)
Philadelphia, Pennsylvania, 19104
Sunita Nasta, MD, 215-662-6933
- Recruiting
The Children's Hospital of Philadelphia Oncology Division, Blood & Marrow Transplant Section (Pediatrics)
Philadelphia, Pennsylvania, 19104
Caitlin Elgarten, MD, 1 267-425-7964
- Completed
University of Pittsburgh Medical Center (Adults only)
Pittsburgh, Pennsylvania, 15232
- Recruiting
Oregon Health and Science University Physicians Pavilion (Adults and Pediatrics)
Portland, Oregon, 97239
Andy Chen, MD, 1 (503) 494-5058
- Completed
University of California Davis Comprehensive Cancer Center (Adults only)
Sacramento, California, 95817
- Recruiting
Washington University School of Medicine (Adults only)
St Louis, Missouri, 63110
Armin Ghobadi, MD, (314) 747-8439
- Completed
Montefiore Medical Center (Adults only)
The Bronx, New York, 10467
- Completed
Montefiore Medical Center (Pediatrics only)
The Bronx, New York, 10467
- Recruiting
MedStar Georgetown University Hospital (Adults and Pediatrics)
Washington D.C., District of Columbia, 20007
Udeme Ekong, MD, 202-444-3514
Australia6 sites, 4 recruiting
- Recruiting
Royal Adelaide Hospital (Adults only)
Adelaide, South Australia, 5000
Devendra Hiwase, MD, 870740000
- Completed
The Prince Charles Hospital (Adults only)
Chermside, Queensland, 4032
- Recruiting
The Royal Children's Hospital Melbourne (Pediatrics only)
Melbourne, Victoria, 3052
Theresa Cole, BM, MRCPCH, FRACP, 0393455522
- Recruiting
Fiona Stanley Hospital (Adults only)
Murdoch, Western Australia, 6150
Duncan Purtill, MD, MBBS, FRACP, FRCPA, (8) 6152 3788
- Recruiting
The Children's Hospital at Westmead (Pediatrics only)
Westmead, New South Wales, 2145
Caroline Bateman, MD, 2 9845 2185
- Completed
Westmead Hospital (Adults only)
Westmead, New South Wales, 2145
Spain6 sites, 6 recruiting
- Recruiting
Hospital Duran i Reynals (Adults and Pediatrics)
Badalona, BARCELONA, 8908
Eva González-Barca, MD, 932274778
- Recruiting
Hospital Universitari Vall d'Hebrón - Institut de Recerca (Adults and Pediatrics)
Barcelona, Barcelona, 08035
Pere Barba, MD, 93 274 6100 ext. 4897
- Recruiting
Hospital General Universitario Gregorio Marañón (Adults and Pediatrics)
Madrid, Madrid, 28009
Rebeca Bailen, MD, 91 426 98 26
- Recruiting
Hospital Universitario Marqués de Valdecilla (Adults and Pediatrics)
Santander, Cantabria, 39008
Lucrecia Yanez, MD, 942202573
- Recruiting
University Hospital Virgen del Rocio (Adults and Pediatrics)
Seville, Spain, 41013
Jose Perez-Simon, MD, 955 013260
- Recruiting
Hospital Universitario La Fe (Adults and Pediatrics)
Valencia, Valencia, 46009
Juan Montoro, MD, 961 245 876
France5 sites
- Completed
Centre Hospitalier Régional Universitaire de Lille (Adults and Pediatrics)
Lille, Hauts-de-France, 59037
- Completed
Hôpital Necker-Enfants Malades (Pediatrics only)
Paris, Île-de-France Region, 75015
- Completed
Hôpital Saint Antoine (Adults only)
Paris, Île-de-France Region, 75571
- Completed
Hôpital Universitaire Pitié Salpêtrière (Adults only)
Paris, Île-de-France Region, 75651
- Completed
Centre Hospitalier Universitaire de Bordeaux (Adults only)
Pessac, Aquitaine, 33600
Italy5 sites
- Completed
Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda (Adults only)
Milan, Milano, 20162
- Completed
Fondazione IRCCS Policlinico San Matteo (Adults and Pediatrics)
Pavia, Pavia, 27100
- Completed
Fondazione Policlinico Universitario Agostino Gemelli (Adults only)
Roma, Roma, 00168
- Completed
Ospedale Pediatrico Bambino Gesu (Pediatrics only)
Roma, Roma, 165
- Completed
Azienda Ospedaliera - Universitaria Città della Salute e della Scienza di Torino (Adults only)
Torino, Torino, 10126
Canada3 sites, 3 recruiting
- Recruiting
Alberta Children's Hospital (Adults and Pediatrics)
Calgary, Alberta, T3B 6A8
Victor Lewis, MD, (403) 955-7203
- Recruiting
Sick Kids (Pediatrics only)
Toronto, Ontario, M5G 1X8
Joerg Krueger, MD, (416) 813-7654
- Recruiting
Princess Margaret Cancer Centre (Adults only)
Toronto, Ontario, M5G 2M9
Igor Novitzky Basso, MD, (416) 315-1147
United Kingdom3 sites, 2 recruiting
- Recruiting
University Hospitals Birmingham NHS Foundation Trust (Adults only)
Birmingham, England, B15 2GW
Sridhar Chaganti, MD, 1214242000
- Completed
King's College Hospital NHS Foundation Trust (Adults only)
London, England, SE5 9RS
- Recruiting
Imperial College Healthcare NHS Trust (Adults only)
London, England, W12 0HS
Eduardo Olavarria, MD, 208 383 2134
Belgium2 sites
- Active, not recruiting
Universitair Ziekenhuis Leuven (Adults and Pediatrics)
Leuven, Flemish Brabant, 3000
- Completed
Centre Hospitalier Universitaire de Liège Site Sart Tilman (Adults and Pediatrics)
Liège, Brussels Capital, 4000
Austria1 site
- Active, not recruiting
Medizinische Universitat Wien (Adults only)
Vienna, Austria, 1090
About this study
Official title: Multicenter, Open-Label, Phase 3 Study of Tabelecleucel for Solid Organ or Allogeneic Hematopoietic Cell Transplant Subjects With Epstein-Barr Virus-Associated Post-Transplant Lymphoproliferative Disease After Failure of Rituximab or Rituximab and Chemotherapy
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.
Read the detailed 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:
- who did not receive chemotherapy and did not have a documented medical reason not to receive chemotherapy (SOT-Ro) or
- 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.
- 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
- Being tested
- tabelecleucel
- 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
- Medical subject headings
- Lymphoproliferative Disorders, Epstein-Barr Virus Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
tabelecleucelBiological
Also called tab-cel®, ATA129, EBV-CTL, Ebvallo®
Tabelecleucel is being investigated as an off-the-shelf, allogeneic T-cell immunotherapy for the treatment of EBV+ malignancies and diseases.
| Study group | Role | What they receive |
|---|---|---|
| Cohort SOT-R (C-SOT-R) | Experimental | Participants with EBV+ PTLD following SOT that has failed rituximab will receive IV tabelecleucel. Receives: 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. Receives: Biological: tabelecleucel |
| Cohort HCT (C-HCT) | Experimental | Participants with EBV+ PTLD following HCT that has failed rituximab containing regimen will receive IV tabelecleucel. Receives: Biological: tabelecleucel |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 2 years
Secondary outcomes (9)
Duration of Response (DOR) in the Analysis Cohorts C-SOT and C-HCT Separately
Measured: 2 years
ORR in the Analysis Cohorts C-SOT and C-HCT Combined
Measured: 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
Measured: 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
Measured: 2 years
Rates of Complete Response (CR) and Partial Response (PR)
Measured: 2 years
Time to Response
Measured: 2 years
Time to Best Response
Measured: 2 years
Overall Survival (OS)
Measured: 2 years
Rates of Allograft Loss or Rejection Episodes (Analysis Cohort C-SOT)
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Jan 2018
- Study start29 Dec 2017
- Primary completion31 May 2030 (estimated)
- Study completionAug 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Epstein-Barr Virus+ Associated Post-transplant Lymphoproliferative Disease (EBV+ PTLD)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 115 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Pierre Fabre Medicament
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03394365
- Sponsor's protocol ID
- ATA129-EBV-302/F60085DL302
- Other IDs
- 2024-516622-57-00
- Acronym
- ALLELE
- Status last verified
- Oct 2026
- First submitted
- 29 Dec 2017
- Last updated
- 19 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 38309282