Summary

at UCSD
study started
estimated completion

Description

Summary

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.

Official Title

Multicenter, Open-Label, Phase 3 Study of Tabelecleucel for Allogeneic Hematopoietic Cell Transplant Subjects With Epstein-Barr Virus-Associated Post-Transplant Lymphoproliferative Disease After Failure of Rituximab

Details

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 2×106 cells/kg on Days 1, 8, and 15, followed by observation through Day 35.

Keywords

Epstein-Barr Virus-Associated Post-Transplant Lymphoproliferative Disease (EBV+ PTLD) Stem Cell Transplant Complications Lymphoproliferative Disorders Epstein-Barr Virus (EBV)-associated Lymphoproliferative Disease (LPD) Hematopoietic Cell Transplantation (HCT) Hematopoietic Stem Cell Transplantation (HSCT) Allogeneic Hematopoietic Cell Transplant Bone Marrow Transplant Complications Cancer After Transplant Cytotoxic T lymphocyte (CTL) Epstein-Barr Virus-specific Cytotoxic T Lymphocytes (EBV-CTL) Allogeneic, Off-The-Shelf T-cell Immunotherapy Post-transplant Lymphoma Epstein-Barr Virus (EBV) Rituximab tabelecleucel

Eligibility

You can join if…

  1. Prior allogeneic hematopoietic cell transplant
  2. A diagnosis of locally-assessed, biopsy-proven EBV+ PTLD with a pathology sample available for central review
  3. Availability of appropriate partially HLA-matched and restricted tabelecleucel cell product
  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). Baseline scans must be of acceptable quality to the central radiology laboratory prior to Cycle 1 Day 1.
  5. 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.
  6. Males and females of any age
  7. Eastern Cooperative Oncology Group (ECOG) performance status <= 3 for subjects aged > 16 years; Lansky score >= 20 for subjects from birth to 16 years
  8. Underlying primary disease, for which the subject underwent transplant, is in morphologic remission
  9. Adequate organ function
  10. Absolute neutrophil count >= 500/µL, with or without cytokine support
  11. 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)
  12. 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
  13. Creatinine < 3 x ULN
  14. . Subject or subject's representative is willing and able to provide written informed consent

You CAN'T join if...

  1. Daily steroids of > 0.5 mg/kg prednisone or glucocorticoid equivalent, methotrexate, or extracorporeal photopheresis
  2. History of central nervous system (CNS) PTLD
  3. Grade >= 2 graft-versus-host disease (GvHD) per the Center for International Blood and Marrow Transplant Research (CIBMTR) consensus grading system at enrollment
  4. 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
  5. Active adenovirus viremia
  6. Need for vasopressor or ventilatory support
  7. Antithymocyte globulin or similar anti-T cell antibody therapy <= 4 weeks prior to Cycle 1 Day 1
  8. 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
  9. Pregnancy
  10. . 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

Locations

  • University of California San Diego Moores Cancer Center (Adults Only) accepting new patients
    La Jolla California 92093 United States
  • Oregon Health and Science University (Adults and Pediatrics) accepting new patients
    Portland Oregon 97239 United States

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
Atara Biotherapeutics
ID
NCT03392142
Phase
Phase 3
Study Type
Interventional
Last Updated