A study for subjects with Epstein-Barr Virus-associated Diseases

Phase 1

Conditions: • EBV+ primary imunodeficiency lymphoproliferative disease (LPD)• EBV+ LPD in the setting of acquired (non-congenital) immunodeficiency • EBV+ post-transplant LPD involving the central nervous system• EBV+ post-transplant LPD where standard first line therapy (rituximab or chemotherapy) is not appropriate, includingCD20-negative disease• EBV+ sarcomas, including leiomyosarcoma• Chronic active Epstein-Barr virus and EBV+ hemophagocytic lymphohistiocytosis
MedDRA version: 21.1Level: PTClassification code 10068349Term: Epstein-Barr virus associated lymphoproliferative disorderSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Therapeutic area: Diseases [C] - Immune System Diseases [C20]

Registration Number: EUCTR2020-000177-25-FR

Lead Sponsor: Atara Biotherapeutics, Inc.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: All

Target Recruitment: 228

Inclusion Criteria

1. ECOG performance status =3 for subjects aged =16 years; Lansky score =20 for subjects from =1 year to <16 years
2. Adequate organ function, unless organ dysfunction is considered to be due to the underlying EBV-associated disease
3. Males and females of any age
For subjects with PID LPD
4. Provided written informed consent and assent, if required by law for pediatric subjects in accordance with the requirements
5. Newly diagnosed or relapsed/refractory 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
6. Systemic and/or CNS disease must be measurable by the at least 1 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 disease measurable by MRI, CT, or by positive cytology with EBV detected in CSF
7. Definitive therapy for the underlying PID is planned
8. Subjects with newly diagnosed disease should be ineligible for standard first-line therapy for EBV+ LPD
For Subjects with AID LPD
9. Newly diagnosed or relapsed/refractory LPD confirmed by at least 1 of the following criteria:
a. Biopsy-proven EBV+ LPD
b. Positive CSF cytology, with or without radiographically measurable intracranial disease, with EBV detected in CSF
10. Systemic and/or CNS disease must be measurable by at least 1 of the following criteria:
a. Systemic disease measurable per Lugano Classification criteria, by PET-diagnostic CT as evidenced by 18F-deoxyglucose avidity
b. CNS disease measurable by MRI, CT, or by positive cytology with EBV detected in CSF
11. Subjects who are HIV+ must meet both of the following criteria:
a. An HIV viral load assessed by RT-PCR below the lower limit of detection, according to the institutional standard, within 6 months of the first dose of tabelecleucel
b. CD4 = 50 cells/µL within 6 months prior to the first dose of tabelecleucel
12. Subjects with newly diagnosed disease should be ineligible for standard first-line therapy for EBV+ LPD
For Subjects with CNS PTLD
13. Newly diagnosed or relapsed/refractory EBV+ CNS PTLD 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
14. Subject 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 disease must be measurable by MRI, CT, or by positive cytology with EBV detected in CSF
15. Subjects with newly diagnosed disease should be ineligible for standard first-line therapy for EBV+ LPD
For subjects with EBV+ PTLD, where standard first line therapy (rituximab and/or chemotherapy) is not appropriate, including CD20-negative disease
16. Newly diagnosed, biopsy-proven EBV+ PTLD
17. Ineligible for standard first-line therapy for EBV+ PTLD
18. Subjects must have systemic disease measurable per Lugano Classification criteria, by PET-diagnostic CT as evidenced by 18F-deoxyglucose avidity
For Subjects with Sarcoma, Including LMS
19. Newly diagnosed or fail

Exclusion Criteria

1. Burkitt, T cell (except in the setting of HLH), NK/T-cell lymphoma/LPD, Hodgkin, or transformed lymphoma
2. Serious known active infections, defined as ongoing uncontrolled adenovirus infection or infections requiring systemic therapy at the time of enrollment
3. 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
4. Need for vasopressor or ventilatory support at the time of enrollment
5. Prior therapy (in order of increasing washout period) prior to enrollment, as follows:
a. Within 4 weeks or 5 half-lives (whichever is shorter):
i. Any investigational product (co-enrollment in a non-interventional study or a study for sample collection only is permitted)
ii. 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. =8 weeks:
i. Cellular therapies: EBV-CTLs, chimeric antigen receptor (CAR) therapies directed at T cells or T cell subsets, donor lymphocyte infusion, other CTLs
ii. Therapies which could impact tabelecleucel function: Anti-thymocyte globulin, alemtuzumab
6. 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
7. Inability or unwillingness to comply with all study procedures
8. 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
9 History of prior allogeneic HCT or SOT

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

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