Summary

at Sacramento, 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 solid organ transplant (SOT) after failure of rituximab or rituximab plus chemotherapy.

Official Title

Multicenter, Open Label, Phase 3 Study of Tabelecleucel for Solid Organ Transplant Subjects With Epstein-Barr Virus-Associated Post-Transplant Lymphoproliferative Disease After Failure of Rituximab or Rituximab and Chemotherapy

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 SOT after failure of rituximab or rituximab plus chemotherapy.

Tabelecleucel cell products will be selected for the subject from a 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.

Subjects will be enrolled into one of two cohorts based on therapy prior to enrollment: Cohort A, for those who have failed rituximab alone; and Cohort B, for those who have failed rituximab and have also received chemotherapy for the treatment of PTLD. Study procedures and product administration will be the same for each cohort.

Tabelecleucel will be administered in cycles lasting 5 weeks (35 days). During each cycle, subjects will receive 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) Solid Organ Transplant Complications Lymphoproliferative Disorders Epstein-Barr Virus (EBV)-associated Lymphoproliferative Disease (LPD) Epstein-Barr Virus (EBV) Cytotoxic T lymphocyte (CTL) Cancer After Transplant Kidney transplant Renal transplant Liver transplant Heart transplant Lung transplant Intestinal transplant Pancreas transplant Post-transplant Lymphoma Solid Organ Transplant (SOT) Bone Marrow Transplant Complications Epstein-Barr Virus-specific Cytotoxic T Lymphocytes (EBV-CTL) Rituximab tabelecleucel

Eligibility

You can join if…

  1. Prior SOT of kidney, liver, heart, lung, pancreas, small bowel, or any combination of these
  2. A diagnosis of locally-assessed, biopsy-proven EBV+ PTLD with a pathology sample available for central review
  3. Availability of appropriate HLA partially-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). For subjects with treated central nervous system (CNS) disease, a head CT and/or brain/spinal magnetic resonance imaging (MRI) as clinically appropriate will be required to follow CNS disease response per Lugano Classification response criteria.
  5. Treatment failure of rituximab monotherapy (Cohort A) or rituximab plus any concurrent or sequentially administered chemotherapy regimen (Cohort B) for 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.

  1. Males and females of any age
  2. Eastern Cooperative Oncology Group (ECOG) performance status <= 3 for subjects aged > 16 years; Lansky score >= 20 for subjects from birth to 16 years
  3. Adequate organ functions:
  4. Absolute neutrophil count >= 1000/μL, with or without cytokine support
  5. Platelet count >= 50,000/μL, with or without transfusion or cytokine support
  6. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin (TBILI) each < 3×ULN; however, ALT, AST, and TBILI each <= 5×ULN is acceptable if the elevation is considered due to PTLD involvement of the liver.

b.Creatinine < 3×ULN

  1. 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. Untreated CNS PTLD or CNS PTLD for which the subject is actively receiving treatment at enrollment
  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 agent (eg ipilimumab, pembrolizumab, nivolumab) within three drug half-lives from the most recent dose to Cycle 1 Day 1
  5. Need for vasopressor or ventilatory support
  6. Antithymocyte globulin or similar anti-T cell antibody therapy <= 4 weeks prior to Cycle 1 Day 1
  7. Treatment with Epstein-Barr virus cytotoxic T lymphocytes or chimeric antigen receptor (CAR) T cells directed against B cells within 8 weeks of Cycle 1 Day 1
  8. Pregnancy
  9. Female of childbearing potential or male with a female partner of childbearing potential unwilling to use a highly effective method of contraception
  10. . Inability to comply with study-related procedures

Locations

  • University of California Davis Comprehensive Cancer Center accepting new patients
    Sacramento California 95817 United States
  • University of California San Diego Moores Cancer Center accepting new patients
    La Jolla California 92093 United States

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
Atara Biotherapeutics
Links
Sign up for this study
ID
NCT03394365
Phase
Phase 3
Study Type
Interventional
Last Updated