TABELECLEUCEL for Post-transplant lymphoproliferative disorder (Epstein-Barr virus-associated)

Inclusion criteria

• {"criterion_text":"- Prior SOT of kidney, liver, heart, lung, pancreas, small bowel, or any combination of these (SOT cohort); or prior allogeneic HCT (HCT cohort).\n- Participant or participant's representative is willing and able to provide written informed consent.\n- A diagnosis of locally-assessed, biopsy-proven EBV+ PTLD.\n- Availability of appropriate partially HLA-matched and restricted tabelecleucel has been confirmed by the sponsor.\n- Measurable, 18F-deoxyglucose (FDG)-avid (Deauville score ≥ 3) systemic disease using Lugano Classification response criteria by positron emission tomography -diagnostic computed tomography, except when contraindicated or mandated by local practice, then magnetic resonance imaging may be used. For Participants with treated central nervous system (CNS) disease, head diagnostic computed tomography and/or brain/spinal magnetic resonance imaging as clinically appropriate will be required to follow CNS disease response per Lugano Classification response criteria.\n- Treatment failure of 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. Treatment failure is defined based on rituximab response as follows: a. Radiographic disease progression per Lugano Classification following a minimum cumulative dose of 1125 mg/m2 rituximab (typically, 3 weekly doses of 375 mg/m2), or b. Failure to achieve CR or PR, defined by Lugano radiographic criteria, after a minimum cumulative dose of 1500 mg/m2 rituximab (typically, 4 weekly doses of 375 mg/m2), or c. Relapse/progression of PTLD after a response to rituximab (SOT-R or HCT cohort) or rituximab plus chemotherapy (SOT-R+C), defined as radiographic and/or biopsy evidence of relapse/progression consistent with PTLD; if the underlying disease for which the subject underwent allogeneic HCT (HCT cohort) was lymphoma, biopsy confirmation of relapsed EBV+ PTLD is required.\n- Males and females of any age.\n- Eastern Cooperative Oncology Group performance status ≤ 3 for Participants aged ≥ 16 years; Lansky score ≥ 20 for Participants < 16 years.\n- For HCT cohort 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.\n- Adequate organ function: a. Absolute neutrophil count ≥ 1000/μL (SOT cohort) or ≥ 500/μL (HCT cohort), with or without cytokine support b. Platelet count ≥ 50,000/μL, with or without transfusion or cytokine support. For HCT cohort, 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, version 5.0) c. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin each < 5 × the upper limit of normal; however, ALT, AST, and total bilirubin each ≤ 10 × the 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 (e.g., elevated prothrombin time due to liver dysfunction, signs/symptoms of liver dysfunction such as asterixis, or similar)."}

Exclusion criteria

• {"criterion_text":"- Currently active Burkitt, T cell, NK/T-cell lymphoma/LPD, Hodgkin, plasmablastic, transformed lymphoma, active hemophagocytic lymphohistiocytosis, or other malignancies requiring systemic therapy.\n- 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.\n- Inability to comply with study-related procedures\n- 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.\n- Daily steroids of > 0.5 mg/kg prednisone or glucocorticoid equivalent, ongoing methotrexate, or extracorporeal photopheresis.\n- 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.\n- Suspected or confirmed grade ≥ 2 graft-versus-host disease per the Center for International Blood and Marrow Transplant Research consensus grading system at enrollment.\n- 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.\n- For HCT cohort only: Active adenovirus viremia.\n- Need for vasopressor or ventilatory support.\n- Antithymocyte globulin or similar anti-T-cell antibody therapy ≤ 4 weeks prior to enrollment.\n- Treatment with EBV-CTLs or chimeric antigen receptor T cells directed against B cells within 8 weeks of enrollment (SOT or HCT cohorts); or unselected donor lymphocyte infusion within 8 weeks of enrollment (HCT cohort only)."}

Primary endpoints

• {"endpoint_text":"- ORR (CR or PR) obtained following administration of tabelecleucel with up to 2 different HLA restrictions in each of the following analysis cohorts: •\tSOT •\tHCT •\tA combined population (SOT-R-Ci, SOT-R+C, and HCT) following administration of commercial product or a product manufactured using a comparable PV","definition_or_measurement_approach":"Objective response rate (ORR) defined as complete response (CR) or partial response (PR); assessed per Lugano Classification response criteria (FDG-PET/diagnostic CT - Deauville score ≥3 for measurable FDG-avid disease) in the defined cohorts (SOT, HCT, combined)."}

Secondary endpoints

• {"endpoint_text":"- DOR in the SOT and HCT cohorts separately.","definition_or_measurement_approach":"Duration of response measured from documented response to progression or death in each cohort (SOT and HCT) separately."}
• {"endpoint_text":"- ORR and DOR in SOT and HCT cohorts combined.","definition_or_measurement_approach":"Objective response rate and duration of response assessed as for primary endpoint, in pooled SOT+HCT population."}
• {"endpoint_text":"- ORR and DOR in subjects who received commercial product or a product manufactured using a comparable PV in the following: SOT-R-Ci and SOT-R+C combined, and separately, HCT","definition_or_measurement_approach":"ORR and DOR measured as above in subgroups defined by product source (commercial or comparable process version) and cohort combinations."}
• {"endpoint_text":"- 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","definition_or_measurement_approach":"Duration of response in the specified combined population receiving commercial or comparable PV product."}
• {"endpoint_text":"- Rates of CR and PR","definition_or_measurement_approach":"Rates of complete response and partial response as per Lugano radiographic criteria."}
• {"endpoint_text":"- Time to response and time to best response","definition_or_measurement_approach":"Time from treatment initiation to first documented response and to best documented response."}
• {"endpoint_text":"- OS","definition_or_measurement_approach":"Overall survival measured from treatment initiation to death from any cause."}
• {"endpoint_text":"- Rates of allograft loss/rejection episodes (for SOT cohort only)","definition_or_measurement_approach":"Incidence of allograft loss or rejection episodes recorded for SOT participants."}

Methods

• Country-specific recruitment arrangements documents are provided (placeholder recruitment arrangements uploaded for France, Italy, Spain, Austria, Belgium) indicating local recruitment procedures are defined per country (documents present but specific content not extractable).
• Physician-to-physician referral (Doctor-to-Doctor referral letter) material present for Spain (K2_ES_Recruitment Material_Dr to Dr Referral Letter_Spanish) indicating recruitment via clinician referral in Spain.

France

Latest Decision Or Authorization Date

21-10-2024

Number Of Sites

5

Number Of Participants

8

Italy

Latest Decision Or Authorization Date

28-10-2024

Number Of Sites

5

Number Of Participants

5

Spain

Latest Decision Or Authorization Date

27-02-2026

Number Of Sites

6

Number Of Participants

5

Austria

Latest Decision Or Authorization Date

26-02-2026

Number Of Sites

1

Number Of Participants

4

Belgium

Latest Decision Or Authorization Date

25-02-2026

Number Of Sites

2

Number Of Participants

4

Primary sponsor

Full Name

Pierre Fabre Medicament

Organisation Type

Pharmaceutical company

Country Of Registered Address

France

Contract research organisations

Name

Icon Clinical Research Limited

Responsibilities

Sponsor duties codes: 1;12;2; contact CTIS-Biotech@iconplc.com; phone +35312912000

Third parties

• {"country":"Germany","full_name":"Fisher Clinical Services GmbH","duties_or_roles":"Sponsor duties codes: 14; contact andrej.kramer@thermofisher.com","organisation_type":"Pharmaceutical company"}
• {"country":"Ireland","full_name":"Icon Clinical Research Limited","duties_or_roles":"Sponsor duties codes: 1; 12; 2; contact CTIS-Biotech@iconplc.com (phone +35312912000)","organisation_type":"Pharmaceutical company"}
• {"country":"Germany","full_name":"Fisher Clinical Services GmbH","duties_or_roles":"Sponsor duties codes: 14; contact andrej.kramer@thermofisher.com","organisation_type":"Pharmaceutical company"}
• {"country":"Germany","full_name":"Fisher Clinical Services GmbH","duties_or_roles":"Sponsor duties codes: 14; contact andrej.kramer@thermofisher.com","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Fortrea Inc.","duties_or_roles":"Sponsor duties codes: 15 (\"Safety report submissions for EU only\"); 8; contact atara@fortrea.com","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Voiant LLC","duties_or_roles":"Sponsor duties codes: 15 (\"Independent radiologic assessments\"); contact hgarrison@voiantclinical.com","organisation_type":"Pharmaceutical company"}
• {"country":"Switzerland","full_name":"Labcorp Central Laboratory Services SARL","duties_or_roles":"Sponsor duties codes: 15 (\"CMV Antibody test,EBV DNA test,EBV-CTLp plasma isolation and PBMC aliquots\"); contact ctasubmissions@labcorp.com","organisation_type":"Pharmaceutical company"}