Tabelecleucel for Solid Organ or Allogeneic Hematopoietic Cell Transplant Participants With Epstein-Barr Virus-Associated Post-Transplant Lymphoproliferative Disease (EBV+ PTLD) After Failure of Rituximab or Rituximab and Chemotherapy

  • STATUS
    Recruiting
  • End date
    Jun 27, 2027
  • participants needed
    66
  • sponsor
    Atara Biotherapeutics
Updated on 27 June 2021
ct scan
systemic disease
platelet count
cancer
remission
rituximab
absolute neutrophil count
organ transplantation
solid organ transplant
neutrophil count
blood transfusion
chemotherapy regimen
myeloid malignancy
primary disease
deoxyglucose

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.

Description

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 210^6 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 tabelecleucel with up to 2 different HLA restrictions (SOT cohort) or up to 4 different HLA restrictions (HCT cohort). The study includes a total of 5 years of follow-up for disease and survival status.

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

NOTE, 29 April 2020: Enrollment is temporarily paused at study site/locations with status "active, not recruiting" due to COVID-19 restrictions.

Details
Condition Lymphoproliferative Disorder, Stem Cell Transplant Complications, EBV-Related PTLD, EBV-Related PTLD, EBV-Related PTLD, EBV-Related PTLD, Epstein-Barr Virus-Related Post-Transplant Lymphoproliferative Disorder, Epstein-Barr Virus-Related Post-Transplant Lymphoproliferative Disorder, Epstein-Barr Virus-Related Post-Transplant Lymphoproliferative Disorder, Epstein-Barr Virus-Related Post-Transplant Lymphoproliferative Disorder, Epstein-Barr Virus-Related Post-Transplant Lymphoproliferative Disorder, Epstein-Barr Virus-Associated Post-transplant Lymphoproliferative Disease (EBV+ PTLD), Solid Organ Transplant Complications, Lymphoproliferative disorders, Epstein-Barr Virus-Associated Post-transplant Lymphoproliferative Disease (EBV+ PTLD), Epstein-Barr Virus-Associated Post-transplant Lymphoproliferative Disease (EBV+ PTLD), Epstein-Barr Virus+ Associated Post-transplant Lymphoproliferative Disease (EBV+ PTLD), Epstein-Barr Virus+ Associated Post-transplant Lymphoproliferative Disease (EBV+ PTLD), Epstein-Barr Virus+ Associated Post-transplant Lymphoproliferative Disease (EBV+ PTLD), Allogeneic Hematopoietic Cell Transplant, Epstein-Barr Virus+ Associated Post-transplant Lymphoproliferative Disease (EBV+ PTLD), Epstein-Barr Virus+ Associated Post-transplant Lymphoproliferative Disease (EBV+ PTLD), Epstein-Barr Virus+ Associated Post-transplant Lymphoproliferative Disease (EBV+ PTLD), Epstein-Barr Virus+ Associated Post-transplant Lymphoproliferative Disease (EBV+ PTLD), Epstein-Barr Virus+ Associated Post-transplant Lymphoproliferative Disease (EBV+ PTLD), Epstein-Barr Virus+ Associated Post-transplant Lymphoproliferative Disease (EBV+ PTLD), Epstein-Barr Virus+ Associated Post-transplant Lymphoproliferative Disease (EBV+ PTLD), Epstein-Barr Virus+ Associated Post-transplant Lymphoproliferative Disease (EBV+ PTLD), Epstein-Barr Virus+ Associated Post-transplant Lymphoproliferative Disease (EBV+ PTLD), Epstein-Barr Virus+ Associated Post-transplant Lymphoproliferative Disease (EBV+ PTLD), Epstein-Barr Virus+ Associated Post-transplant Lymphoproliferative Disease (EBV+ PTLD), Epstein-Barr Virus+ Associated Post-transplant Lymphoproliferative Disease (EBV+ PTLD), Epstein-Barr Virus+ Associated Post-transplant Lymphoproliferative Disease (EBV+ PTLD), Epstein-Barr Virus+ Associated Post-transplant Lymphoproliferative Disease (EBV+ PTLD), Epstein-Barr Virus+ Associated Post-transplant Lymphoproliferative Disease (EBV+ PTLD), Epstein-Barr Virus+ Associated Post-transplant Lymphoproliferative Disease (EBV+ PTLD), Epstein-Barr Virus+ Associated Post-transplant Lymphoproliferative Disease (EBV+ PTLD), lymphoproliferative disease, Epstein-Barr Virus+ Associated Post-transplant Lymphoproliferative Disease (EBV+ PTLD), Epstein-Barr Virus+ Associated Post-transplant Lymphoproliferative Disease (EBV+ PTLD), Epstein-Barr Virus+ Associated Post-transplant Lymphoproliferative Disease (EBV+ PTLD), Epstein-Barr Virus+ Associated Post-transplant Lymphoproliferative Disease (EBV+ PTLD), Epstein-Barr Virus+ Associated Post-transplant Lymphoproliferative Disease (EBV+ PTLD), Epstein-Barr Virus+ Associated Post-transplant Lymphoproliferative Disease (EBV+ PTLD), Epstein-Barr Virus+ Associated Post-transplant Lymphoproliferative Disease (EBV+ PTLD), Epstein-Barr Virus+ Associated Post-transplant Lymphoproliferative Disease (EBV+ PTLD), Epstein-Barr Virus+ Associated Post-transplant Lymphoproliferative Disease (EBV+ PTLD), Epstein-Barr Virus+ Associated Post-transplant Lymphoproliferative Disease (EBV+ PTLD), Epstein-Barr Virus+ Associated Post-transplant Lymphoproliferative Disease (EBV+ PTLD), Epstein-Barr Virus+ Associated Post-transplant Lymphoproliferative Disease (EBV+ PTLD), Epstein-Barr Virus+ Associated Post-transplant Lymphoproliferative Disease (EBV+ PTLD), Epstein-Barr Virus+ Associated Post-transplant Lymphoproliferative Disease (EBV+ PTLD), Epstein-Barr Virus+ Associated Post-transplant Lymphoproliferative Disease (EBV+ PTLD)
Treatment ATA129, tabelecleucel
Clinical Study IdentifierNCT03394365
SponsorAtara Biotherapeutics
Last Modified on27 June 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

Prior SOT of kidney, liver, heart, lung, pancreas, small bowel, or any combination of these (SOT cohort); or prior allogeneic HCT (HCT cohort)
A diagnosis of locally-assessed, biopsy-proven EBV+ PTLD
Availability of appropriate partially HLA-matched and restricted tabelecleucel has been confirmed by the sponsor
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
Treatment failure of rituximab monotherapy (SOT cohort, subgroup A or HCT cohort) or rituximab plus chemotherapy (SOT cohort, subgroup B) for treatment of PTLD
Eastern Cooperative Oncology Group performance status 3 for subjects aged 16 years; Lansky score 20 for subjects < 16 years
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
Adequate organ function
Absolute neutrophil count 1000/L, (SOT cohort) or 500/L (HCT cohort), with or without cytokine support
Platelet count 50,000/L, with or without transfusion or cytokine support. For HCT cohort, platelet count < 50,000/L but 20,000/L, 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)
Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin each < 5 the upper limit of normal; however, ALT, AST, and total bilirubin each 10 upper limit of normal 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
Subject or subject's representative is willing and able to provide written informed consent

Exclusion Criteria

Burkitt lymphoma, classical Hodgkin lymphoma, or any T cell lymphoma
Daily steroids of > 0.5 mg/kg prednisone or glucocorticoid equivalent, ongoing methotrexate, or extracorporeal photopheresis
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
Suspected or confirmed grade 2 graft-versus-host disease (GvHD) per the Center for International Blood and Marrow Transplant Research consensus grading system at enrollment
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
For HCT cohort: active adenovirus viremia
Need for vasopressor or ventilatory support
Antithymocyte globulin or similar anti-T cell antibody therapy 4 weeks prior to enrollment
Treatment with Epstein-Barr virus cytotoxic T lymphocytes or chimeric antigen receptor 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)
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
Inability to comply with study-related procedures
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