A study for subjects with Epstein-Barr Virus-associated Diseases
- 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, including CD20-negative disease• EBV+ sarcomas, including leiomyosarcoma• Chronic active Epstein-Barr virus and EBV+ hemophagocytic lymphohistiocytosisMedDRA 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-IT
- 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
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
[please refer to protocol synopsis as here there is not enough space to write all criteria]
Are the trial subjects under 18? yes
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 107
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 23
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 Main Objective: To determine the clinical benefit of tabelecleucel (allogeneic Epstein- Barr virus-specific cytotoxic T lymphocytes [EBV-CTLs]) in subjects with EBV-associated diseases as measured by the objective response rate (ORR);Secondary Objective: To evaluate additional clinically relevant outcomes in EBV-associated diseases treated with tabelecleucel;Primary end point(s): The ORR obtained following administration of tabelecleucel with up to 4 different human leukocyte antigen (HLA) restrictions;Timepoint(s) of evaluation of this end point: Monitored throughout the study
- Secondary Outcome Measures
Name Time Method Secondary end point(s): • Overall survival (OS)<br>• Duration of response (DOR)<br>• Progression-free survival (PFS)<br>• For EBV-associated lymphoproliferative disease in the setting of primary imunodeficiency (EBV+ PID LPD) and chronic active EBV/hemophagocytic lymphohistiocytosis (CAEBV/HLH) cohorts who are eligible for allogeneic hematopoietic cell transplant (HCT):<br>o Number of subjects who reach definitive therapy (ie, allogeneic HCT) for the underlying disease<br>o Time to allogeneic HCT<br>• For EBV+ sarcoma cohort, including leiomyosarcoma (LMS)<br>o Clinical benefit rate<br>o ORR by immune response evaluation criteria in solid tumors (iRECIST)<br>criteria;Timepoint(s) of evaluation of this end point: Monitored throughout the study