Description:
The purpose of this study is to assess the efficacy and safety of tabelecleucel in
participants with Epstein-Barr virus (EBV) associated diseases.
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
Drug | Synonyms | Arms |
---|
Tabelecleucel | tab-cel®, ATA129, EBV-CTLs | CAEBV 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
Name | Type | Description | Interventions |
---|
EBV+ PID LPD | Experimental | Participants with newly diagnosed or relapsed/refractory EBV+ PID LPD will receive IV tabelecleucel. | |
EBV+ AID LPD | Experimental | Participants with newly diagnosed or relapsed/refractory EBV+ AID LPD will receive IV tabelecleucel. | |
EBV+ PTLD CNS | Experimental | Participants with newly diagnosed or relapsed/refractory EBV+ PTLD CNS will receive IV tabelecleucel. | |
EBV+ PTLD (ineligible for first-line therapy or CD20 negative) | Experimental | Participants with EBV+ PTLD where standard first line therapy (rituximab or chemotherapy) is not appropriate, including CD20 negative disease will receive IV tabelecleucel. | |
EBV+ sarcoma, including LMS | Experimental | Participants with newly diagnosed or failed systemic first-line therapy for EBV+ sarcoma will receive IV tabelecleucel. | |
CAEBV or EBV viremia with HLH | Experimental | Participants with newly diagnosed or previously treated CAEBV or EBV viremia with HLH will receive IV 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