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

Phase 3

Recruiting

• Conditions: Solid Organ Transplant Complications; Lymphoproliferative Disorders; Epstein-Barr Virus+ Associated Post-transplant Lymphoproliferative Disease (EBV+ PTLD); Allogeneic Hematopoietic Cell Transplant; Stem Cell Transplant Complications
• Interventions: Biological: tabelecleucel

• Registration Number: NCT03394365
• Lead Sponsor: Pierre Fabre Medicament

Brief 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.

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:

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.

Study Timeline

• Study Start: 2017-12-29
• Study First Submitted: 2017-12-29
• Study First Submitted QC: 2018-01-04
• Study First Posted: 2018-01-09
• Status Verified: 2025-06
• Last Update Submitted: 2025-07-09
• Last Update Posted: 2025-07-14
• Primary Completion: 2025-08
• Study Completion: 2027-06-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 66

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 subjects 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 subjects aged ≥ 16 years; Lansky score ≥ 20 for subjects < 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 subject 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 subject 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. Subject or subject'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 subject is actively receiving CNS-directed chemotherapy (systemic or intrathecal) or radiotherapy at enrollment. NOTE:Subjects 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
12. 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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Cohort SOT-R (C-SOT-R)	tabelecleucel	Participants with EBV+ PTLD following SOT that has failed rituximab will receive IV tabelecleucel.
Cohort SOT-R+C (C-SOT-R+C)	tabelecleucel	Participants with EBV+ PTLD following SOT that has failed both rituximab and chemotherapy will receive IV tabelecleucel.
Cohort HCT (C-HCT)	tabelecleucel	Participants with EBV+ PTLD following HCT that has failed rituximab containing regimen will receive IV tabelecleucel.

Primary Outcome Measures

Name	Time	Method
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	2 years

Secondary Outcome Measures

Name	Time	Method
Time to Response	2 years
Duration of response (DOR) in the Analysis Cohorts C-SOT and C-HCT Separately	2 years
ORR and DOR in the Analysis Cohorts C-SOT and C-HCT Combined	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	2 years
DOR in the Analysis Cohort of the 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	2 years
Rates of Complete Response (CR) and Partial Response (PR)	2 years
Time to Best Response	2 years
Overall Survival (OS)	2 years
Rates of Allograft Loss or Rejection Episodes (Analysis Cohort C-SOT)	2 years

Trial Locations

Locations (71)

City of Hope (Adults and Pediatrics); 🇺🇸 Duarte, California, United States

University of California San Diego Moores Cancer Center (Adults only); 🇺🇸 La Jolla, California, United States

Loma Linda University Medical Center (Adults only); 🇺🇸 Loma Linda, California, United States

Children's Hospital Los Angeles, Div. of Research Immunology/BMT (Adults and Pediatrics); 🇺🇸 Los Angeles, California, United States

UCLA Medical Center (Adults and Pediatrics); 🇺🇸 Los Angeles, California, United States

University of California Davis Comprehensive Cancer Center (Adults only); 🇺🇸 Sacramento, California, United States

Yale University (Adults and Pediatrics); 🇺🇸 New Haven, Connecticut, United States

MedStar Georgetown University Hospital (Adults and Pediatrics); 🇺🇸 Washington, District of Columbia, United States

University of Florida (Adults and Pediatrics); 🇺🇸 Gainesville, Florida, United States

University of Miami/Jackson Memorial Hospital (Adults only); 🇺🇸 Miami, Florida, United States

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