Clinical Trials /

A Study to Evaluate Tabelecleucel in Participants With Epstein-barr Virus-associated Diseases

NCT04554914

Description:

The purpose of this study is to assess the efficacy and safety of tabelecleucel in participants with Epstein-Barr virus (EBV) associated diseases.

Related Conditions:
  • Hemophagocytic Lymphohistiocytosis
  • Immunodeficiency-Associated Lymphoproliferative Disorder
  • Leiomyosarcoma
  • Post-Transplant Lymphoproliferative Disorder
  • Sarcoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Study to Evaluate Tabelecleucel in Participants With Epstein-barr Virus-associated Diseases
  • Official Title: An Open-label, Single-arm, Multicohort, Phase 2 Study to Assess the Efficacy and Safety of Tabelecleucel in Subjects With Epstein-Barr Virus-associated Diseases

Clinical Trial IDs

  • ORG STUDY ID: ATA129-EBV-205
  • SECONDARY ID: 2020-000177-25
  • NCT ID: NCT04554914

Conditions

  • Epstein-Barr Virus (EBV)-Associated Diseases
  • EBV+ Lymphoproliferative Disease With Primary Immunodeficiency (PID LPD)
  • EBV+ Lymphoproliferative Disease With Acquired (Non-congenital) Immunodeficiency (AID LPD)
  • EBV+ Posttransplant Lymphoproliferative Disease in Central Nervous System (CNS PTLD)
  • EBV+ Post-transplant Lymphoproliferative Disease (EBV+ PTLD)
  • Solid Organ Transplant Complications
  • Lymphoproliferative Disorders
  • Allogeneic Hematopoietic Cell Transplant
  • Stem Cell Transplant Complications
  • EBV+ Sarcomas
  • Leiomyosarcoma
  • Chronic Active Epstein-Barr Virus (CAEBV)
  • Chronic Active Epstein-Barr Virus With Hemophagocytic Lymphohistiocytosis (HLH)
  • Lymphohistiocytosis, Hemophagocytic

Interventions

DrugSynonymsArms
Tabelecleuceltab-cel®, ATA129, EBV-CTLsCAEBV or EBV viremia with HLH

Purpose

The purpose of this study is to assess the efficacy and safety of tabelecleucel for the treatment of Epstein-Barr virus (EBV) associated diseases in participants who are newly diagnosed or relapsed/refractory to prior treatment.

Detailed Description

      This is a multicenter, multicohort, open label, single-arm, Phase 2 study to assess the
      efficacy and safety of tabelecleucel for the treatment of EBV-associated diseases in
      participants who are newly diagnosed or relapsed/refractory to prior treatment. Newly
      diagnosed or relapsed/refractory participants will be enrolled in one of the following
      cohorts:

        -  EBV+ lymphoproliferative disease (LPD) in the setting of primary immunodeficiency (PID)
           (ie, PID LPD)

        -  EBV+ LPD in the setting of acquired (non-congenital) immunodeficiency (AID) (ie, AID
           LPD)

        -  EBV+ posttransplant lymphoproliferative disorder involving the central nervous system
           (CNS PTLD)

        -  EBV+ PTLD where standard first line therapy (rituximab or chemotherapy) is not
           appropriate, including CD20 negative disease

        -  EBV+ sarcomas, including leiomyosarcoma (LMS)

        -  Chronic active EBV (CAEBV), including CAEBV with hemophagocytic lymphohistiocytosis
           (HLH)

      Tabelecleucel will be administered in cycles lasting 5 weeks (35 days). During each cycle,
      participants will receive tabelecleucel at a dose of 2 x 10^6 cells/kg intravenously (IV)
      weekly for 3 weeks, followed by observation through Day 35. Treatment will continue until
      maximal disease progression, unacceptable toxicity, or initiation of nonprotocol therapy for
      the underlying disease. For participants in the sarcoma cohort, treatment will continue until
      disease progression, unacceptable toxicity, or 2-year safety visit. Participants who fail to
      respond to initial tabelecleucel treatment may continue tabelecleucel with a different human
      leukocyte antigen (HLA) restriction (termed a Restriction Switch); up to 3 Restriction
      Switches may be performed for any participant.

      Participants will complete a safety follow-up visit at 30 days after the last dose followed
      by quarterly follow-up (after the last dose) until disease progression, initiation of
      non-study treatment for EBV-associated disease or 2-year safety visit at 24-month after first
      dose.

      An adaptive 2-stage design will be used for each cohort in this study. For each cohort,
      approximately 8 participants will be enrolled in Stage 1. The decision to move to Stage 2
      enrollment will be based on an interim analysis of the first 8 evaluable participants in the
      cohort using investigator's assessment (per defined radiologic, clinical, and/or laboratory
      response criteria). The number of participants enrolled in Stage 2 for each cohort will
      depend on the number of observed responders in Stage 1.
    

Trial Arms

NameTypeDescriptionInterventions
EBV+ PID LPDExperimentalParticipants with newly diagnosed or relapsed/refractory EBV+ PID LPD will receive IV tabelecleucel.
  • Tabelecleucel
EBV+ AID LPDExperimentalParticipants with newly diagnosed or relapsed/refractory EBV+ AID LPD will receive IV tabelecleucel.
  • Tabelecleucel
EBV+ PTLD CNSExperimentalParticipants with newly diagnosed or relapsed/refractory EBV+ PTLD CNS will receive IV tabelecleucel.
  • Tabelecleucel
EBV+ PTLD (ineligible for first-line therapy or CD20 negative)ExperimentalParticipants with EBV+ PTLD where standard first line therapy (rituximab or chemotherapy) is not appropriate, including CD20 negative disease will receive IV tabelecleucel.
  • Tabelecleucel
EBV+ sarcoma, including LMSExperimentalParticipants with newly diagnosed or failed systemic first-line therapy for EBV+ sarcoma will receive IV tabelecleucel.
  • Tabelecleucel
CAEBV or EBV viremia with HLHExperimentalParticipants with newly diagnosed or previously treated CAEBV or EBV viremia with HLH will receive IV tabelecleucel.
  • Tabelecleucel

Eligibility Criteria

        Inclusion Criteria:

          -  Diagnosis of EBV+ disorder

          -  Eastern Cooperative Oncology Group performance status <= 3 for participants aged >= 16
             years; Lansky score >= 20 for participants from 1 year to < 16 years

          -  Adequate organ function test results, unless organ dysfunction is considered to be due
             to the underlying LPD by the investigator

        Disease-Related inclusion criteria:

          -  For participants with PID LPD:

               -  Newly diagnosed or relapsed/refractory LPD histologically confirmed by
                  biopsy-proven EBV+ LPD or positive cerebrospinal fluid (CSF) cytology with or
                  without radiographically measurable intracranial disease with EBV detected in CSF

               -  Participant may have systemic only disease, CNS only disease, or both

               -  Definitive therapy (eg, allogeneic HCT, gene therapy) for the underlying PID is
                  planned

          -  For participants with AID LPD:

               -  Newly diagnosed or relapsed/refractory LPD histologically confirmed by
                  biopsy-proven EBV+ LPD or CNS disease must be measurable by MRI/CT or EBV must be
                  detected in CSF by lumbar puncture cytology

               -  Participant may have systemic only disease, CNS only disease, or both

               -  Participants who are human immunodeficiency virus positive (HIV+) must meet both
                  of the following criteria: Have an HIV viral load assessed by reverse
                  transcription-polymerase chain reaction (RT-PCR) below the lower limit of
                  detection and CD4 >= 50 cells/μL within 6 months prior to the first dose of
                  tabelecleucel.

          -  For participants with CNS PTLD:

               -  Newly diagnosed or relapsed/refractory EBV+ CNS PTLD histologically confirmed by
                  biopsy-proven EBV+ CNS PTLD or positive CSF cytology with or without
                  radiographically measurable intracranial disease with EBV detected in CSF

               -  Participant may have systemic and CNS disease or CNS only disease

          -  For participants with sarcoma, including LMS:

               -  Newly diagnosed or failed systemic first-line therapy for EBV+ sarcoma

               -  Biopsy-proven EBV+ sarcoma

               -  Measurable disease using diagnostic PET/CT and/or MRI following RECIST 1.1
                  criteria

          -  For participants with CAEBV:

               -  Newly diagnosed or previously treated CAEBV

               -  Detectable EBV viremia on at least 2 occasions at a minimum of 90 days apart

               -  At least 3 active clinical findings (per Kimura H, et al. Front Immunol.
                  2017;8:1867).

          -  For participants with EBV+ viremia with HLH:

               -  Newly diagnosed or previously treated EBV+ viremia with HLH

               -  A molecular diagnosis consistent with HLH-2004 trial (per Henter JI, et al.
                  Pediatr Blood Cancer. 2007;48:124-31) OR 5 or more of the clinical symptoms (per
                  Jordan MB, et al. Blood. 2011;118:4041-4052).

        Exclusion Criteria:

          -  Burkitt, T-cell (except in the setting of HLH), natural killer/T-cell lymphoma/LPD,
             Hodgkin, or transformed lymphoma

          -  Serious known active infections, defined as ongoing uncontrolled adenovirus infection
             or infections requiring active therapy, within 2 weeks prior to enrollment

          -  Suspected or confirmed Grade >= 2 acute graft-versus-host disease (GvHD) per the
             Center for International Blood and Marrow Transplant Research (CIBMTR) consensus
             grading system or extensive chronic GvHD per National Institutes of Health (NIH)
             consensus criteria at the time of the enrollment

          -  Need for vasopressor or ventilatory support

          -  Prior therapy (in order of increasing washout period) prior to enrollment as: within 4
             weeks or 5 half-lives (whichever is shorter) for any investigational product; and/or
             within <= 8 weeks for cellular therapies (EBV-CTLs, chimeric antigen receptor
             therapies directed at T cells or T-cell subsets, donor lymphocyte infusion, other
             CTLs); and/or therapies which could impact tabelecleucel function (anti-thymocyte
             globulin, alemtuzumab)

          -  Unwilling to use protocol specified contraceptive methods

          -  Women who are pregnant or breastfeeding

          -  For participants with involvement of CNS (CNS LPD or CNS PTLD):

               -  Participant actively receiving chemotherapy (systemic or intrathecal), or
                  radiotherapy treatment at the time of enrollment

               -  Daily steroids of > 0.5 mg/kg prednisone or glucocorticoid equivalent, ongoing
                  methotrexate, or extracorporeal photopheresis (protocol-specified dexamethasone
                  is permitted and concludes by the time of enrollment)

          -  For participants with PID LPD or AID LPD: history of prior allogeneic HCT or solid
             organ transplant

          -  For participants with EBV+ viremia: Participants with EBV+ viremia who do not meet
             inclusion criteria for CAEBV or HLH
      
Maximum Eligible Age:N/A
Minimum Eligible Age:N/A
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Objective response rate (ORR)
Time Frame:2 years
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Overall survival (OS)
Time Frame:2 years
Safety Issue:
Description:
Measure:Duration of response (DOR)
Time Frame:2 years
Safety Issue:
Description:
Measure:Progression-free survival (PFS)
Time Frame:2 years
Safety Issue:
Description:
Measure:For EBV+ AID LPD and CAEBV/HLH: Number of participants who reach definitive therapy (ie, allogeneic HCT) for the underlying disease
Time Frame:2 years
Safety Issue:
Description:
Measure:For EBV+ AID LPD and CAEBV/HLH: Time to allogeneic HCT
Time Frame:2 years
Safety Issue:
Description:
Measure:For EBV+ sarcomas, including LMS: Clinical benefit rate
Time Frame:2 years
Safety Issue:
Description:
Measure:For EBV+ sarcomas, including LMS: ORR by immune response evaluation criteria in solid tumors (iRECIST) criteria
Time Frame:2 years
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Atara Biotherapeutics

Trial Keywords

  • Allogeneic, Off-The-Shelf T-cell Immunotherapy
  • Epstein-Barr Virus (EBV)
  • Epstein-Barr Virus-specific Cytotoxic T lymphocyte (EBV-CTL)
  • Solid Organ Transplant (SOT)
  • Hematopoietic Cell Transplant (HCT)

Last Updated

September 14, 2020