Tabelecleucel for Allogeneic Hematopoietic Cell Transplant Subjects With Epstein-Barr Virus-Associated Post-Transplant Lymphoproliferative Disease (EBV+ PTLD) After Failure of Rituximab
Purpose
This is a multicenter, open label, single-arm, phase 3 study to assess the efficacy and safety of tabelecleucel for the treatment of Epstein-Barr virus-associated post-transplant lymphoproliferative disease (EBV+ PTLD) in the setting of allogeneic hematopoietic cell transplant (HCT) after failure of rituximab.
Conditions
- Epstein-Barr Virus-Associated Post-Transplant Lymphoproliferative Disease (EBV+ PTLD)
- Stem Cell Transplant Complications
- Lymphoproliferative Disorders
Eligibility
- Eligible Ages
- All ages
- Eligible Genders
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- Prior allogeneic hematopoietic cell transplant
- A diagnosis of locally-assessed, biopsy-proven EBV+ PTLD with a pathology sample available for central review
- Availability of appropriate partially HLA-matched and restricted tabelecleucel cell product
- Measurable, 18F-deoxyglucose (FDG)-avid (Deauville score >= 3) systemic disease (using Lugano Classification response criteria) by positron emission tomography (PET)-diagnostic computed tomography (CT). Baseline scans must be of acceptable quality to the central radiology laboratory prior to Cycle 1 Day 1.
- Failure of rituximab for first-line treatment of PTLD. Note: Subjects with CD20 negative disease are eligible to enroll without prior anti-CD20 therapy after failure of first-line treatment (reduction of immunosuppression is not considered first-line therapy) and discussion with the sponsor's medical monitor.
- Males and females of any age
- Eastern Cooperative Oncology Group (ECOG) performance status <= 3 for subjects aged > 16 years; Lansky score >= 20 for subjects from birth to 16 years
- Underlying primary disease, for which the subject underwent transplant, is in morphologic remission
- Adequate organ function
- Absolute neutrophil count >= 500/µL, with or without cytokine support
- Platelet count >= 50,000/µL, with or without transfusion support; 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 6 months (where grading of the bleeding is determined per the National Cancer Institute's Common Terminology Criteria for Adverse Events [CTCAE], version 5.0)
- Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin (TBILI) each < 3 x the upper limit of normal (ULN); however, ALT, AST, and TBILI each <= 5 x ULN is acceptable if the elevation is considered by the investigator to be due to PTLD involvement of the liver
- Creatinine < 3 x ULN
- Subject or subject's representative is willing and able to provide written informed consent
Exclusion Criteria
- Daily steroids of > 0.5 mg/kg prednisone or glucocorticoid equivalent, methotrexate, or extracorporeal photopheresis
- History of central nervous system (CNS) PTLD
- Grade >= 2 graft-versus-host disease (GvHD) per the Center for International Blood and Marrow Transplant Research (CIBMTR) consensus grading system at enrollment
- Ongoing or recent use of a checkpoint inhibitor (eg, nivolumab, pembrolizumab, ipilimumab) within three drug half-lives from the most recent dose to Cycle 1 Day 1
- Active adenovirus viremia
- Need for vasopressor or ventilatory support
- Antithymocyte globulin or similar anti-T cell antibody therapy <= 4 weeks prior to Cycle 1 Day 1
- Treatment with Epstein-Barr virus cytotoxic T lymphocytes, chimeric antigen receptor (CAR)-T cells directed against B cells, or unselected donor lymphocyte infusion (DLI) within 8 weeks of Cycle 1 Day 1
- Pregnancy
- Female of childbearing potential or male with a female partner of childbearing potential unwilling to use a highly effective method of contraception
- Inability to comply with study-related procedures
Study Design
- Phase
- Phase 3
- Study Type
- Interventional
- Intervention Model
- Single Group Assignment
- Primary Purpose
- Treatment
- Masking
- None (Open Label)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Experimental tabelecleucel |
Tabelecleucel will be administered in cycles lasting 5 weeks (35 days). During each cycle, subjects will receive intravenous (IV) tabelecleucel at a dose of 2 x 10^6 cells/kg on Days 1, 8 and 15, followed by observation through Day 35. Treatment will continue until maximal response, unacceptable toxicity, initiation of non-protocol therapy, or failure of multiple tabelecleucel cell products. |
|
Recruiting Locations
Nashville, Tennessee 37232
More Details
- NCT ID
- NCT03392142
- Status
- Recruiting
- Sponsor
- Atara Biotherapeutics
Detailed Description
This is a multicenter, open label, single-arm, phase 3 study to assess the efficacy and safety of tabelecleucel for the treatment of EBV+ PTLD in the setting of allogeneic HCT after failure of rituximab.
Tabelecleucel will be selected for the subject from the bank of available tabelecleucel cell products based on matching >= 2 human leukocyte antigen (HLA) alleles, at least one of which is a restricting HLA allele, shared between the tabelecleucel donor and the subject's EBV+ PTLD. Sites will provide high resolution subject and subject's graft donor HLA typing results and other information as required by the protocol.
Tabelecleucel will be administered in cycles lasting 5 weeks (35 days). During each cycle, subjects will receive intravenous (IV) tabelecleucel at a dose of 2×10^6 cells/kg on Days 1, 8, and 15, followed by observation through Day 35.