Summary

at La Jolla, California and other locations
study started
estimated completion

Description

Summary

The purpose of this study is to determine the clinical benefit and characterize the safety profile of tabelecleucel for the treatment of Epstein-Barr virus-associated post-transplant lymphoproliferative disease (EBV+ PTLD) in the setting of (1) solid organ transplant (SOT) after failure of rituximab and rituximab plus chemotherapy or (2) allogeneic hematopoietic cell transplant (HCT) after failure of rituximab.

Official Title

Multicenter, Open Label, Phase 3 Study of Tabelecleucel for Solid Organ or Allogeneic Hematopoietic Cell 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, 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 and rituximab plus chemotherapy (SOT cohort) or HCT after failure of rituximab (HCT cohort).

Enrollment will be preceded by confirmation of availability of partially human leukocyte antigen (HLA) matched and restricted tabelecleucel for the participant.

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, participants will receive intravenous tabelecleucel at a dose of 2×106 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 tabelecleucel with up to 2 different HLA restrictions (SOT cohort) or up to 4 different HLA restrictions (HCT cohort).

This protocol has been amended to include the HCT cohort from clinical study ATA129-EBV-301 (NCT03392142).

Keywords

Epstein-Barr Virus+ Associated Post-transplant Lymphoproliferative Disease (EBV+ PTLD) Solid Organ Transplant Complications Lymphoproliferative Disorders Allogeneic Hematopoietic Cell Transplant Stem Cell Transplant Complications 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) Hematopoietic Cell Transplant (HCT) Hematopoietic Stem Cell Transplantation (HSCT) Allogeneic, Off-The-Shelf T-cell Immunotherapy Rituximab tabelecleucel

Eligibility

You can join if…

  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, a head 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 monotherapy (SOT cohort, subgroup A or HCT cohort) or rituximab plus chemotherapy (SOT cohort, subgroup B) for treatment of PTLD.
  6. Eastern Cooperative Oncology Group performance status ≤ 3 for subjects aged > 16 years; Lansky score ≥ 20 for subjects from birth to 16 years
  7. 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
  8. Adequate organ function
  9. Absolute neutrophil count ≥ 1000/μL, (SOT cohort) or ≥ 500/μL (HCT cohort), with or without cytokine support
  10. 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)
  11. 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).
  12. Subject or subject's representative is willing and able to provide written informed consent

You CAN'T join if...

  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.

  1. Suspected or confirmed grade ≥ 2 graft-versus-host disease (GvHD) per the Center for International Blood and Marrow Transplant Research (CIBMTR) consensus grading system at enrollment
  2. 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
  3. For HCT cohort: active adenovirus viremia
  4. Need for vasopressor or ventilatory support
  5. Antithymocyte globulin or similar anti-T cell antibody therapy ≤ 4 weeks prior to enrollment
  6. Treatment with Epstein-Barr virus cytotoxic T lymphocytes 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)
  7. . 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
  8. . 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
  • University of California Davis Comprehensive Cancer Center (Adults only) accepting new patients
    Sacramento California 95817 United States

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
Atara Biotherapeutics
ID
NCT03394365
Phase
Phase 3
Study Type
Interventional
Last Updated