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 allogeneic, off‑the‑shelf Epstein–Barr virus (EBV)–specific T‑cell immunotherapy for EBV‑positive post‑transplant lymphoproliferative disease (EBV+ PTLD) after failure of at least one prior therapy. It received EU marketing authorization under exceptional circumstances on December 16, 2022, for adults and children ≥2 years; the Summary of Product Characteristics was last updated February 18, 2025. As of September 2, 2025, it has FDA Priority Review in the United States with a PDUFA target action date of January 10, 2026, following a January 16, 2025 Complete Response Letter related to third‑party manufacturing inspection issues (not efficacy/safety), and subsequent resubmission; clinical holds linked to those issues were lifted in May 2025. (ema.europa.eu, reuters.com, onclive.com, investors.atarabio.com)

Mechanism of action

Tabelecleucel consists of partially HLA‑matched, EBV‑specific cytotoxic T lymphocytes derived from healthy donors, expanded ex vivo by stimulation with donor EBV‑infected B‑cell lines. After infusion, these T cells recognize EBV antigens (for example, latent proteins such as EBNA and LMP family antigens) presented in an HLA‑restricted manner on malignant or infected B cells, and eliminate them. Dosing is 2 × 10^6 cells/kg intravenously on days 1, 8, and 15 of 35‑day cycles, with response‑guided continuation. (ema.europa.eu, pmc.ncbi.nlm.nih.gov)

Efficacy

Phase 3, multicenter, open‑label ALLELE trial (Lancet Oncology 2024): Among 43 treated patients (14 HSCT, 29 SOT) with EBV+ PTLD after failure of rituximab ± chemotherapy, objective response rate (ORR) was 50% in HSCT and 52% in SOT. Responses were durable in a subset (durable responses ≥6 months reported), with ongoing follow‑up. (pubmed.ncbi.nlm.nih.gov)
Updated ALLELE results (ASH 2024 abstract; ASTCT journal 2025 in‑press abstract): In 75 treated patients (49 SOT, 26 HCT), ORR was 50.7% overall (CR 28.0%, PR 22.7%), median time to response 1.1 months, and median duration of response 23.0 months. Median overall survival (OS) was 18.4 months; 1‑year OS was 78.7% for responders vs 28.2% for non‑responders. (ash.confex.com, astctjournal.org)
Multicenter expanded‑access cohort (Blood Advances 2024): In 26 patients (14 HCT, 12 SOT) with relapsed/refractory EBV+ PTLD after rituximab ± chemotherapy, investigator‑assessed ORR was 65% overall (50% HCT; 83% SOT). Estimated 1‑ and 2‑year OS were both 70% overall; responders had markedly higher OS than non‑responders. (pmc.ncbi.nlm.nih.gov)

These findings support clinically meaningful and often durable responses in a population with historically poor outcomes after failure of initial therapy. (pubmed.ncbi.nlm.nih.gov, pmc.ncbi.nlm.nih.gov)

Safety

Across studies, tabelecleucel was generally well tolerated. In ALLELE (n=43), serious TEAEs occurred in 53% and fatal TEAEs in 12%, but none of the fatal events were considered treatment‑related. Notably, no cytokine release syndrome, ICANS, infusion reactions, marrow rejection, graft‑versus‑host disease, or solid‑organ graft rejection were reported as related to tabelecleucel. In the 75‑patient update, serious and fatal TEAEs occurred in approximately 61–65% and 18–19% by cohort, with no fatal treatment‑related TEAEs and no GVHD or organ rejection attributed to therapy. The EMA product information lists common adverse reactions (e.g., pyrexia, diarrhea, fatigue, cytopenias, liver enzyme elevations) and notes authorization under exceptional circumstances with ongoing data collection. (pubmed.ncbi.nlm.nih.gov, astctjournal.org, ema.europa.eu)

HealthScout AI Analysis

Goal: 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 patients following solid organ transplant (SOT) or allogeneic hematopoietic cell transplant (HCT).

Patients: Children and adults of any age with biopsy‑proven EBV+ PTLD after SOT (kidney, liver, heart, lung, pancreas, small bowel, or combinations) or after allogeneic HCT who have failed rituximab (SOT or HCT) or rituximab plus chemotherapy (SOT). Patients must have FDG‑avid, measurable disease per Lugano, ECOG ≤3 (≥16 years) or Lansky ≥20 (<16 years), adequate organ function, and availability of a partially HLA‑matched tabelecleucel product. Key exclusions include T‑cell lymphomas, untreated or actively treated CNS PTLD, grade ≥2 GVHD, recent checkpoint inhibitor use, need for vasopressors or ventilatory support, recent ATG or EBV‑CTL/CAR‑T, and significant uncontrolled comorbidities.

Design: Multicenter, open‑label, nonrandomized phase 3 trial with parallel experimental cohorts: SOT after failure of rituximab (C‑SOT‑R), SOT after failure of rituximab plus chemotherapy (C‑SOT‑R+C), and HCT after failure of rituximab (C‑HCT). Enrollment is contingent upon availability of a partially HLA‑matched product. Efficacy and safety are assessed over treatment cycles with up to 5 years of follow‑up.

Treatments: Tabelecleucel, an allogeneic, off‑the‑shelf EBV‑specific cytotoxic T‑cell therapy composed of partially HLA‑matched donor T cells expanded ex vivo to recognize EBV antigens (e.g., EBNA, LMP) on malignant/infected B cells in an HLA‑restricted manner. Dosing is 2 × 10^6 cells/kg IV on days 1, 8, and 15 of each 35‑day cycle, repeated until maximal response, toxicity, alternative therapy, or failure after up to 2 HLA restrictions in SOT or up to 4 in HCT. Across phase 3 and expanded‑access reports to date, objective response rates around 50% have been observed in both SOT and HCT populations after rituximab ± chemotherapy, with a subset achieving durable responses and favorable survival among responders; safety has been generally acceptable without signals for treatment‑related GVHD or graft rejection.

Outcomes: Primary: Objective response rate in C‑SOT, C‑HCT, and a combined population treated with commercial/comparable process product, assessed over 2 years. Key secondary endpoints include duration of response in each cohort; ORR in combined cohorts; ORR and DOR in chemotherapy‑ineligible and rituximab+chemotherapy SOT subgroups and in HCT; complete and partial response rates; time to response and time to best response; overall survival; and, in SOT, rates of allograft loss or rejection.

Burden on patient: Moderate. Therapy requires IV infusions on days 1, 8, and 15 of 35‑day cycles with imaging (PET‑CT or MRI) and clinical assessments per Lugano, along with routine labs to monitor organ function, cytopenias, and EBV‑PTLD status. No intensive pharmacokinetic sampling is described, but travel for thrice‑per‑cycle infusions and periodic scans is necessary. CNS imaging may be required if CNS disease is present. The need for HLA‑matched product confirmation and potential switching across HLA restrictions may extend treatment logistics, but procedures are generally consistent with advanced PTLD care without additional invasive biopsies beyond diagnostic or response‑driven needs.

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)