A study for subjects after organ or cell transplantation after failure of prior treatment

Phase 1

• Conditions: Epstein-Barr Virus-Associated Post-Transplant Lymphoproliferative Disease; 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); MedDRA version: 21.0Level: LLTClassification code 10075146Term: Post transplant 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: EUCTR2017-002949-30-ES
• Lead Sponsor: Atara Biotherapeutics, Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2019-12-20
• Last Update Posted: 9 September 2024

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 66

Inclusion Criteria

1. Prior SOT of kidney, liver, heart, lung, pancreas, small bowel, or any combination of these (SOT cohort);
or prior allogeneic HCT (HCT cohort).
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, head diagnostic 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
(SOT subgroup A or HCT cohort) or rituximab plus any concurrent or sequentially administered
chemotherapy regimen (SOT subgroup B) 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 subgroup A or HCT cohort) or
rituximab plus chemotherapy (SOT subgroup B), 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.
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 from birth to 16 years.
8. 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 subject underwent transplant must be in morphologic remission.
9. 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 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)
c. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin (TBILI)
each < 5 × the upper limit of normal (ULN); however, ALT, AST, and TBILI each = 10 × ULN 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 (eg,
elevated prothrombin time due to liver dysfunction, signs/symptoms of liver dysfunction such as
asterixis, or similar).
10. Subject or subject’s representative is willing and able to provide written informed consent.
Are the trial subjects under 18? yes

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 per the Center for International Blood and Marrow Transplant Research (CIBMTR) 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 HCT cohort only: 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 EBV-CTLs or chimeric antigen receptor (CAR) 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).
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

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified