tabelecleucel for Epstein-Barr virus-associated primary immunodeficiency lymphoproliferative disease (PID LPD) | Epstein-Barr virus-associated post-transplant lymphoproliferative disorder (PTLD) | Epstein-Barr virus-associated sarcoma (including leiomyosarcoma) | Epstein-Barr virus-associated CNS post-transplant lymphoproliferative disorder

Inclusion criteria

• {"criterion_text":"- 1.ECOG performance status ≤3 for participants aged ≥16 years; Lansky score ≥20 for participants from ≥1 year to <16 years"}
• {"criterion_text":"- 4. Provided written informed consent and assent, if required by law for pediatric subjects in accordance with the requirements"}
• {"criterion_text":"- 5. For participants with PID LPD - Relapsed and/or refractory (R/R) or newly diagnosed PID LPD for whom the standard first line therapy is inappropriate, as determined by the investigator. LPD confirmed by at least 1 of the following: a. Biopsy-proven EBV+ LPD b. Positive CSF cytology with or without radiographically measurable intracranial disease with EBV detected in CSF. Participants with R/R disease must have had at least one prior line of systemic therapy and one of the following: a.Radiographic disease progression per Lugano Classification during or after treatment b.Failure to achieve a CR or PR (defined by Lugano radiographic criteria) after standard first-line therapy"}
• {"criterion_text":"- 6. Subjects may have systemic disease only, systemic and CNS disease or CNS disease only, meeting one of the following criteria: a. Systemic disease measurable per Lugano Classification criteria, by PET-CT as evidenced by 18F-deoxyglucose avidity, except when contraindicated or mandated by local practice, then MRI may be used. b.CNS only disease measurable by MRI, CT, or by cytology and flow cytometry with EBV detected in CSF"}
• {"criterion_text":"- 7. For participants with CNS PTLD. R/R or newly diagnosed CNS PTLD for whom the standard first line therapy is inappropriate, as determined by the investigator, confirmed by at least 1 of the following: a.Biopsy-proven EBV+ CNS PTLD, b.Positive CSF cytology, with or without radiographically measurable intracranial disease, with EBV detected in CSF. Participants with R/R disease must have had at least one prior line of systemic therapy and one of the following: a.Radiographic disease progression per Lugano Classification during or after treatment b.Failure to achieve a CR or PR (defined by Lugano radiographic criteria) after standard first-line therapy"}
• {"criterion_text":"- 8. Participants may have systemic and CNS disease, or CNS disease only meeting the following criteria: a.When present, systemic disease measurable per Lugano Classification criteria, by PET-diagnostic CT as evidenced by 18F-deoxyglucose avidity, except when contraindicated or mandated by local practice, then MRI may be used. b.CNS only disease must be measurable by MRI, CT, or by cytology and flow cytometry with EBV detected in CSF. Contrast-enhanced CT scans may be substituted in patients in whom MRI is medically contraindicated (e.g., cardiac pacemaker) or unavailable. For participants with EBV+1L PTLD where standard first line therapy (rituximab and/or chemotherapy) is inappropriate, including CD20negative disease"}
• {"criterion_text":"- 9. Biopsy-proven EBV+ PTLD for whom standard first line therapy is inappropriate"}
• {"criterion_text":"- 10. Subjects must have systemic disease measurable per Lugano Classification criteria, by PET-diagnostic CT as evidenced by 18Fdeoxyglucose avidity."}
• {"criterion_text":"- 11. For participants with Sarcoma, including LMS, or smooth muscle tumors. EBV+ sarcoma or smooth muscle tumor with rapidly progressive disease defined as progressive disease per RECIST 1.1 criteria as documented radiographically within a 6-month interval prior to enrollment."}
• {"criterion_text":"- 12. Biopsy-proven EBV+ sarcoma meeting one of the following criteria: a.Pathologically confirmed EBV+ Leiomyosarcoma b.EBV+ Sarcoma or smooth muscle tumor"}
• {"criterion_text":"- 13. Measurable disease using CT, and/or MRI following RECIST 1.1 criteria"}
• {"criterion_text":"- 2. Adequate organ function, unless organ dysfunction is considered to be due to the underlying EBV-associated disease"}
• {"criterion_text":"- 3. Males and females of any age"}

Exclusion criteria

• {"criterion_text":"- Currently active Burkitt, T cell, natural killer (NK)/T-cell lymphoma/LPD, Hodgkin, plasmablastic, transformed lymphoma, active hemophagocytic lymphohistiocytosis, or other malignancies requiring systemic therapy"}
• {"criterion_text":"- Any conditions that may put the study outcomes at undue risk: \ta. Life expectancy < 60 days \tb. Any life-threatening illness, medical condition, or organ system dysfunction that, in the investigator's opinion, could compromise the subject's safety or put the study outcomes at undue risk"}
• {"criterion_text":"- Exclusion Criteria for Participants with PID LPD or AID LPD (cohort closed in Amendment 3 after completion of stage 1) only History of prior allogeneic HCT or SOT"}
• {"criterion_text":"- Exclusion Criteria for participants with EBV+ 1L PTLD, where standard first-line therapy (rituximab and/or chemotherapy) is inappropriate, including CD20-negative disease Prior systemic therapy for PTLD"}
• {"criterion_text":"- Serious known active infections, defined as ongoing uncontrolled adenovirus infection or infections requiring systemic therapy at the time of enrollment, or known history of human immunodeficiency virus (HIV) infection"}
• {"criterion_text":"- Suspected or confirmed grade ≥ 2 acute (GvHD) per the CIBMTR consensus grading system or moderate/severe chronic GvHD per NIH consensus criteria at the time of the enrollment"}
• {"criterion_text":"- Need for vasopressor or ventilatory support at the time of enrollment."}
• {"criterion_text":"- Prior therapy (in order of increasing washout period) prior to enrollment, as follows: a. Within 4 weeks or 5 half-lives (whichever is shorter): \t\ti. Any investigational product (co-enrollment in a non-interventional study or a study for sample collection only is permitted) \t\tii. Any chemotherapy (systemic or intrathecal), targeted small molecule therapy, or antibody/biologic therapy. Note: prior anti-CD20 antibody use is permitted within the washout period if a subsequent disease response assessment indicates disease progression. B. Within 8 weeks: \t\ti. Prior tabelecleucel (>8 weeks prior to enrollment) is permitted (in consultation with the Medical Monitor) if response was obtained or if usual protocol-directed therapeutic options were not exhausted (e.g., restriction switch options) \t\tii. Cellular therapies: chimeric antigen receptor (CAR) therapies directed at T cells or T cell subsets, donor lymphocyte infusion, other CTLs, or virus-specific T cells \t\tiii. Therapies which could impact tabelecleucel function: Anti-thymocyte globulin, alemtuzumab C. Any prior treatment with EBV-CTLs with the exception of tabelecleucel as above"}
• {"criterion_text":"- Female who is breastfeeding or pregnant"}
• {"criterion_text":"- Any of the following while undergoing treatment with tabelecleucel and for 90 days after the last dose (details are specified in the body of the protocol): For females of childbearing potential: 1) unwilling to use a highly effective method of contraception (i.e., one that can achieve a failure rate of less than 1% per year when used consistently and correctly) or 2) unwilling to refrain from donating eggs For males: 1) unwilling to use a condom during sexual intercourse or 2) unwilling to refrain from donating sperm or 3) has a female partner of childbearing potential who is unwilling to use a highly effective method of contraception (refer to protocol Section 5.6.4)"}
• {"criterion_text":"- Inability or unwillingness to comply with all study procedures"}
• {"criterion_text":"- Ongoing need for daily steroids of >0.5 mg/kg prednisone or glucocorticoid equivalent ongoing methotrexate, or extracorporeal photopheresis. For subjects with CNS disease, protocol specified dexamethasone is permitted"}

Primary endpoints

• {"endpoint_text":"- The ORR obtained following administration of tabelecleucel with up to different human leukocyte antigen (HLA) restrictions","definition_or_measurement_approach":"Objective response rate (ORR) as the measure of clinical benefit (ORR). Primary endpoint text indicates ORR after tabelecleucel administration (translations specify up to two HLA restrictions)."}

Secondary endpoints

• {"endpoint_text":"- Overall survival (OS)","definition_or_measurement_approach":"Overall survival measured as time from study entry (or defined baseline) to death from any cause (OS)."}
• {"endpoint_text":"- Duration of response (DOR)","definition_or_measurement_approach":"Duration of response measured as time from documented response to disease progression or death (DOR)."}
• {"endpoint_text":"- Progression-free survival (PFS)","definition_or_measurement_approach":"Progression-free survival measured as time from study entry (or defined baseline) to radiographic or clinical progression or death (PFS)."}
• {"endpoint_text":"- For EBV-associated lymphoproliferative disease in the setting of primary imunodeficiency (EBV+ PID LPD) cohort: Number of participants who reach definitive therapy (i.e., allogeneic HCT) for the underlying disease. Time to definitive therapy.","definition_or_measurement_approach":"Count of participants who proceed to definitive therapy (allogeneic hematopoietic cell transplantation) and time-to-definitive-therapy measurement."}
• {"endpoint_text":"- For EBV+ sarcoma cohort, including leiomyosarcoma (LMS), or smooth muscle tumors: Clinical benefit rate. ORR by immune response evaluation criteria in solid tumors (iRECIST) criteria [Seymour 2017]","definition_or_measurement_approach":"Clinical benefit rate and ORR assessed per iRECIST (immune response evaluation criteria in solid tumors) [Seymour 2017]."}

Methods

• Referral letters to clinicians (country-specific referral letter documents listed: e.g., K2_*_Recruitment Material_Referral letter in German/French/Spanish)
• Printed recruitment flyers (e.g., K2_AT_Recruitment Material_Flyer_German)
• Website postings / online recruitment via Sarcoma Alliance website (K2_AT_Recruitment Material_ Sarcoma Alliance Website_Screenshots)
• Country-specific recruitment procedures and placeholder recruitment arrangements documents exist for BE, IT, AT, FR, ES (K1_*_Recruitment Procedure and placeholder documents)

Belgium

Earliest CTIS Part Ii Submission Date

24-09-2024

Latest Decision Or Authorization Date

09-02-2026

Processing Time Days

503

Number Of Sites

3

Number Of Participants

12

Italy

Earliest CTIS Part Ii Submission Date

24-09-2024

Latest Decision Or Authorization Date

10-02-2026

Processing Time Days

504

Number Of Sites

3

Number Of Participants

19

Austria

Earliest CTIS Part Ii Submission Date

24-09-2024

Latest Decision Or Authorization Date

16-02-2026

Processing Time Days

510

Number Of Sites

1

Number Of Participants

9

France

Earliest CTIS Part Ii Submission Date

24-09-2024

Latest Decision Or Authorization Date

16-02-2026

Processing Time Days

510

Number Of Sites

3

Number Of Participants

12

Spain

Earliest CTIS Part Ii Submission Date

24-09-2024

Latest Decision Or Authorization Date

11-02-2026

Processing Time Days

505

Number Of Sites

3

Number Of Participants

12

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: 1,12,2,6,7,8

Name

Fortrea Inc.

Third parties

• {"country":"United States","full_name":"Voiant LLC","duties_or_roles":"Medical image analysis/ review - X-ray, MRI, ultrasound, etc.","organisation_type":"Pharmaceutical company"}
• {"country":"Switzerland","full_name":"Labcorp Central Laboratory Services SARL","duties_or_roles":"MV antibody, EBV DNA load","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Fortrea Inc.","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"Ireland","full_name":"Icon Clinical Research Limited","duties_or_roles":"Sponsor duties codes: 1,12,2,6,7,8","organisation_type":"Pharmaceutical company"}
• {"country":"Germany","full_name":"Fisher Clinical Services GmbH","duties_or_roles":"Sponsor duties code: 14","organisation_type":"Pharmaceutical company"}