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 a donor-derived T-cell therapy for relapsed or refractory Epstein–Barr virus–positive post-transplant lymphoproliferative disease (EBV+ PTLD). It is authorised in the European Union for patients aged 2 years and older who have received prior treatment; it remains investigational in the United States. (ema.europa.eu)

Mechanism of action

The therapy contains T cells selected for their ability to recognise Epstein–Barr virus (EBV). Their receptors recognise viral peptides displayed with specific human leukocyte antigen (HLA) molecules on infected cells, enabling the T cells to kill those cells. A product lot is selected according to the patient’s HLA profile; the T cells are not genetically modified. (ema.europa.eu)

Efficacy

In the single-arm phase 3 ALLELE trial, a peer-reviewed analysis of 43 treated patients reported an objective response in 7 of 14 (50%) recipients of a hematopoietic cell transplant and 15 of 29 (52%) recipients of a solid-organ transplant. A subsequent conference abstract covering 75 patients reported an overall response rate of 50.7% (38/75), including 28.0% complete responses; median response duration was 23 months. Because ALLELE has no randomised control group, these results do not establish how much benefit tabelecleucel provides relative to other care. (pubmed.ncbi.nlm.nih.gov)

Safety

In the 75-patient update, serious adverse events occurring after treatment were reported in approximately 63% of patients, and fatal adverse events in approximately 19%; none of the fatal events was judged treatment-related. The investigators reported no cytokine-release syndrome or treatment-related graft-versus-host disease or organ rejection. These findings need to be interpreted in the context of a small trial involving seriously ill patients. (ash.confex.com)

TrialFetch AI Analysis

Goal: Assess the clinical benefit and safety of tabelecleucel in Epstein–Barr virus–positive post-transplant lymphoproliferative disease (EBV+ PTLD) after rituximab-based treatment failure.

Patients: Children and adults with biopsy-proven, measurable EBV+ PTLD after solid-organ transplantation who have failed rituximab alone or rituximab plus chemotherapy, or after allogeneic hematopoietic cell transplantation who have failed rituximab. Enrollment requires an available partially HLA-matched tabelecleucel product and adequate performance status and organ function.

Design: Multicenter, open-label, nonrandomized study with separate solid-organ transplant and hematopoietic cell transplant cohorts. There is no control arm. Disease and survival follow-up continues for up to 5 years.

Treatments: All participants receive intravenous tabelecleucel at 2 × 10^6 cells/kg on days 1, 8, and 15 of each 35-day cycle, with treatment continuing until maximal response, unacceptable toxicity, or another stopping criterion. Tabelecleucel is a donor-derived, non-genetically modified T-cell therapy selected to recognize EBV peptides presented by a patient-compatible HLA molecule and kill EBV-infected cells. In a published analysis of this single-arm trial, objective responses occurred in 7 of 14 hematopoietic cell transplant recipients and 15 of 29 solid-organ transplant recipients; without a control group, the relative benefit remains uncertain.

Outcomes: The primary outcome is objective response rate over 2 years in specified solid-organ transplant, hematopoietic cell transplant, and combined analysis populations. Secondary outcomes include duration of response, complete and partial response rates, time to response and best response, overall survival, and solid-organ allograft loss or rejection.

Burden on patient: Moderate to high. Each treatment cycle requires three intravenous infusion visits within 15 days, followed by observation through day 35; additional cycles may be needed. Response assessment requires PET-CT or alternative imaging, and disease and survival follow-up extends to 5 years. No intensive pharmacokinetic sampling or additional research biopsies are specified.

Last updated: Sep 2026

Eligibility

Caution: ClinicalTrials.gov appears to have newer eligibility criteria than the version saved here. Review the current criteria in ClinicalTrials.gov.

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

TrialFetch AI Analysis

Eligibility

Show Criteria

Sites (71)

The Children's Hospital at Westmead (Pediatrics only)

Westmead Hospital (Adults 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)

Alberta Children's Hospital (Adults and Pediatrics)

Princess Margaret Cancer Centre (Adults only)

Sick Kids (Pediatrics only)

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)

Imperial College Healthcare NHS Trust (Adults only)

University Hospitals Birmingham NHS Foundation Trust (Adults only)

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

Loma Linda University Medical Center (Adults only)

MedStar Georgetown University Hospital (Adults and Pediatrics)

University of Miami/Jackson Memorial Hospital (Adults only)

Arthur M. Blank Hospital (Pediatrics)

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

Loyola University Medical Center (Adults and Pediatrics)

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

Washington University School of Medicine (Adults only)

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

Duke Cancer Institute (Adults and Pediatrics)

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

Cleveland Clinic Foundation (Adults and Pediatrics)

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

Hospital of the University of Pennsylvania (Adults only)

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

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

Baylor Scott and White Research Institute (Adults only)

MD Anderson Cancer Center (Pediatrics and Adult)

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

Medizinische Universitat Wien (Adults only)

Universitair Ziekenhuis Leuven (Adults and Pediatrics)

Medical University of South Carolina (Adults and Pediatrics)

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

Centre Hospitalier Universitaire de Bordeaux (Adults only)

Centre Hospitalier Régional Universitaire de Lille (Adults and Pediatrics)

Hôpital Necker-Enfants Malades (Pediatrics only)

Hôpital Saint Antoine (Adults only)

Hôpital Universitaire Pitié Salpêtrière (Adults only)

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

Fondazione IRCCS Policlinico San Matteo (Adults and Pediatrics)

Fondazione Policlinico Universitario Agostino Gemelli (Adults only)

Ospedale Pediatrico Bambino Gesu (Pediatrics only)

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

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

City of Hope (Adults and Pediatrics)

UCLA Medical Center (Adults and Pediatrics)

University of California Davis Comprehensive Cancer Center (Adults only)

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

Yale University (Adults and Pediatrics)

University of Florida (Adults and Pediatrics)

Winship Cancer Institute (Adults only)

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

University of Maryland School of Medicine (Adults only)

Columbia University Medical Center (Adults and Pediatrics)

Memorial Sloan Kettering Cancer Center (Adults and Pediatrics)

Montefiore Medical Center (Adults only)

Montefiore Medical Center (Pediatrics only)

Weill Cornell Medicine (Adults only)