Summary

at La Jolla, California and other locations
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 accepting new patients
    La Jolla California 92093 United States
  • Children's Hospital of Colorado accepting new patients
    Aurora Colorado 80045 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