Trial: Tabelecleucel for Solid Organ or Alloge…

Trial Details

Sponsor: Pierre Fabre Medicament (industry)

Phase: 3

Start date: Dec. 29, 2017

Planned enrollment: 66

Trial ID: NCT03394365

More trial details at ClinicalTrials.gov

Show Summary from Sponsor

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.

More details:

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.

Investigational Drug AI Analysis

Show for: tabelecleucel (Ebvallo)

Overview

Tabelecleucel (Ebvallo) is an off‑the‑shelf, allogeneic, Epstein–Barr virus (EBV)–specific T‑cell therapy for EBV‑positive post‑transplant lymphoproliferative disease (EBV+ PTLD). It received EU marketing authorization on December 16, 2022, for adults and children ≥2 years with relapsed/refractory EBV+ PTLD after at least one prior therapy (for solid‑organ transplant, prior therapy includes chemotherapy unless inappropriate). In the United States, FDA issued a Complete Response Letter in January 2025 related to third‑party manufacturing; the resubmitted BLA received Priority Review in July 2025 with a PDUFA target action date of January 10, 2026. (ema.europa.eu)

Mechanism of action

Tabelecleucel consists of EBV‑specific cytotoxic T cells derived from seropositive third‑party donors. Donor T cells are primed ex vivo against EBV‑infected B cells from the same donor and expanded without genetic modification. After infusion, these HLA‑restricted T cells recognize and eliminate EBV‑infected cells in the recipient. (ema.europa.eu)

Efficacy

Pivotal single‑arm phase 3 (ALLELE; multicenter, open‑label) in relapsed/refractory EBV+ PTLD after HCT or SOT: among the first 43 treated patients, objective response rate (ORR) was 51.2% (CR 26%, PR 25%); median duration of response (DOR) 23.0 months; median overall survival (OS) 18.4 months; 1‑year OS 84.4% for responders vs 34.8% for non‑responders. (sciencedirect.com)
Updated ALLELE cohort (conference update; n=75): ORR 50.7% overall (SOT 51.0%, HCT 50.0%); median DOR 23 months; median OS 18.4 months. (ashpublications.org)
EU EPAR summary of the 43‑patient dataset: responses in 15/29 SOT and 7/14 HCT; several responses >6 months. (ema.europa.eu)
Multicenter Expanded Access Protocol (Blood Advances 2024; n=26 treated: 14 HCT, 12 SOT): investigator‑assessed ORR 65.4% overall (HCT 50%, SOT 83.3%); estimated 1‑ and 2‑year OS 70% overall; responses associated with markedly higher survival. (scholars.duke.edu)
CNS‑involved EBV+ PTLD pooled analysis (Transplantation and Cellular Therapy 2023; n=18): ORR 77.8%; 1‑ and 2‑year OS 70.6% and 54.9%. (astctjournal.org)

Context: EBV+ PTLD after failure of initial therapy has historically poor survival measured in weeks to a few months, underscoring the unmet need. (ashpublications.org)

Safety

In ALLELE (Lancet Oncology) and subsequent ASH update, no cytokine release syndrome, tumor flare reaction, immune‑effector neurotoxicity, or graft‑versus‑host disease/organ rejection events were reported as related to tabelecleucel; serious TEAEs occurred but fatal events were not considered treatment‑related. (sciencedirect.com)
EU product information lists common adverse reactions (e.g., pyrexia, diarrhea, fatigue, anemia) and identifies tumor flare reaction and graft‑versus‑host disease as important risks warranting monitoring. (ema.europa.eu)
Expanded‑access reports describe good tolerability with absence of CRS, ICANS, tumor flare, or transplant rejection attributed to therapy. (scholars.duke.edu)

HealthScout AI Analysis

Goal: To evaluate the clinical benefit and safety of tabelecleucel in Epstein-Barr virus–positive post-transplant lymphoproliferative disease (EBV+ PTLD) after failure of rituximab with or without chemotherapy in solid organ transplant recipients, and after failure of rituximab in allogeneic hematopoietic cell transplant recipients.

Patients: Children and adults of any age with biopsy-proven, FDG-avid EBV+ PTLD following solid organ transplant (kidney, liver, heart, lung, pancreas, small bowel, or combinations) who have failed rituximab alone or rituximab plus chemotherapy, including those ineligible for chemotherapy, or following allogeneic HCT who have failed rituximab. Key requirements include availability of a partially HLA-matched tabelecleucel product, ECOG ≤3 (≥16 years) or Lansky ≥20 (<16 years), adequate organ function, and measurable disease per Lugano criteria. Exclusions include Burkitt, classical Hodgkin, and T-cell lymphomas, untreated or actively treated CNS PTLD, recent checkpoint inhibitor use, significant GVHD in HCT, and need for vasopressors or ventilatory support.

Design: Multicenter, open-label, nonrandomized phase 3 trial with parallel experimental cohorts in SOT after rituximab failure (with or without prior chemotherapy) and in allogeneic HCT after rituximab failure. Enrollment requires confirmation of an appropriate partially HLA-matched product. Follow-up extends to 5 years for disease and survival.

Treatments: Tabelecleucel, an allogeneic, off-the-shelf EBV-specific cytotoxic T-cell therapy derived from healthy donors, partially HLA-matched to the recipient. It targets EBV antigens presented on malignant or infected B cells and eliminates them via HLA-restricted cytotoxicity. Dosing is 2 × 10^6 cells/kg IV on days 1, 8, and 15 of 35-day cycles, continued until maximal response, unacceptable toxicity, nonprotocol therapy, or predefined failure criteria; up to 2 different HLA restrictions may be used in SOT and up to 4 in HCT. Prior studies, including the phase 3 ALLELE program, show objective response rates around 50% with durable responses in a substantial subset and a tolerable safety profile without treatment-related GVHD or organ rejection reported.

Outcomes: Primary: Objective response rate in prespecified cohorts and a combined population receiving commercial or comparable-process product over 2 years. Secondary: Duration of response; combined ORR; ORR and DOR within cohort subsets receiving commercial/comparable product; time to response; time to best response; overall survival; rates of complete and partial responses; and, in SOT, rates of allograft loss or rejection episodes, all assessed over approximately 2 years, with extended survival follow-up to 5 years.

Burden on patient: Moderate. Patients receive IV infusions on days 1, 8, and 15 of each 35-day cycle with imaging assessments per Lugano criteria and routine laboratory monitoring for cytopenias, liver function, and infectious complications. Upfront HLA matching is required but does not entail additional procedures beyond standard typing. There are no intensive pharmacokinetic schedules, but serial PET-CT or MRI and frequent clinical visits, particularly early in treatment, increase time and travel demands. Long-term follow-up for up to 5 years adds visit or contact requirements but aligns with oncologic surveillance after transplant.

Last updated: Oct 2025

Eligibility

Show Criteria

Inclusion Criteria:

1. Prior SOT of kidney, liver, heart, lung, pancreas, small bowel, or any combination of 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 has been confirmed by the sponsor.

4. 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.

5. 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.

6. Males and females of any age.

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

8. 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.

9. Adequate organ function.

1. Absolute neutrophil count ≥ 1000/μL, (C-SOT) or ≥ 500/μL (C-HCT), with or without cytokine support.

2. 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).

3. 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.

10. Participant or participant's representative is willing and able to provide written informed consent.

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 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.

4. 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.

5. 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.

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 to enrollment.

9. 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).

10. 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.

11. Inability to comply with study-related procedures.

Trial Details

Show Summary from Sponsor

More details:

Investigational Drug AI Analysis

Show for: tabelecleucel (Ebvallo)

Overview

Mechanism of action

Efficacy

Safety

Further reading

HealthScout AI Analysis

Eligibility

Show Criteria

Sites (71)

Westmead Hospital (Adults only)

The Children's Hospital at Westmead (Pediatrics only)

The Prince Charles Hospital (Adults only)

Royal Adelaide Hospital (Adults only)

The Royal Children's Hospital Melbourne (Pediatrics only)

Fiona Stanley Hospital (Adults only)

Medizinische Universitat Wien (Adults only)

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

Universitair Ziekenhuis Leuven (Adults and Pediatrics)

Alberta Children's Hospital (Adults and Pediatrics)

Sick Kids (Pediatrics only)

Princess Margaret Cancer Centre (Adults only)

Centre Hospitalier Universitaire de Bordeaux (Adults only)

Centre Hospitalier Régional Universitaire de Lille (Adults and Pediatrics)

Hôpital Necker-Enfants Malades (Pediatrics only)

Hôpital Universitaire Pitié Salpêtrière (Adults only)

Hôpital Saint Antoine (Adults only)

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

Fondazione IRCCS Policlinico San Matteo (Adults and Pediatrics)

Ospedale Pediatrico Bambino Gesu (Pediatrics only)

Fondazione Policlinico Universitario Agostino Gemelli (Adults only)

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

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

Hospital Duran i Reynals (Adults and Pediatrics)

Hospital Universitario Marqués de Valdecilla (Adults and Pediatrics)

Hospital General Universitario Gregorio Marañón (Adults and Pediatrics)

University Hospital Virgen del Rocio (Adults and Pediatrics)

Hospital Universitario La Fe (Adults and Pediatrics)

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

Imperial College Healthcare NHS Trust (Adults only)

University Hospitals Birmingham NHS Foundation Trust (Adults only)

Loma Linda University Medical Center (Adults only)

UCLA Medical Center (Adults and Pediatrics)

University of California Davis Comprehensive Cancer Center (Adults only)

City of Hope (Adults and Pediatrics)

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

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

Yale University (Adults and Pediatrics)

MedStar Georgetown University Hospital (Adults and Pediatrics)

University of Florida (Adults and Pediatrics)

University of Miami/Jackson Memorial Hospital (Adults only)

Winship Cancer Institute (Adults only)

Arthur M. Blank Hospital (Pediatrics)

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

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

Loyola University Medical Center (Adults and Pediatrics)

University of Maryland School of Medicine (Adults only)

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

Washington University School of Medicine (Adults only)

Montefiore Medical Center (Adults only)

Weill Cornell Medicine (Adults only)

Columbia University Medical Center (Adults and Pediatrics)

Memorial Sloan Kettering Cancer Center (Adults and Pediatrics)

Montefiore Medical Center (Pediatrics only)

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

Duke Cancer Institute (Adults only)

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

Cleveland Clinic Foundation (Adults and Pediatrics)

Nationwide Children's Hospital (Pediatrics only)

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

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

University of Pittsburgh Medical Center (Adults only)

Hospital of the University of Pennsylvania (Adults only)

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

Medical University of South Carolina (Adults and Pediatrics)