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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03394365




Registration number
NCT03394365
Ethics application status
Date submitted
29/12/2017
Date registered
9/01/2018
Date last updated
6/11/2024

Titles & IDs
Public title
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
Scientific 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
Secondary ID [1] 0 0
ATA129-EBV-302
Universal Trial Number (UTN)
Trial acronym
ALLELE
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Epstein-Barr Virus+ Associated Post-transplant Lymphoproliferative Disease (EBV+ PTLD) 0 0
Solid Organ Transplant Complications 0 0
Lymphoproliferative Disorders 0 0
Allogeneic Hematopoietic Cell Transplant 0 0
Stem Cell Transplant Complications 0 0
Condition category
Condition code
Infection 0 0 0 0
Other infectious diseases
Cardiovascular 0 0 0 0
Diseases of the vasculature and circulation including the lymphatic system
Inflammatory and Immune System 0 0 0 0
Other inflammatory or immune system disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Other - tabelecleucel

Experimental: Cohort SOT-R (C-SOT-R) - Participants with EBV+ PTLD following SOT that has failed rituximab will receive IV tabelecleucel.

Experimental: Cohort SOT-R+C (C-SOT-R+C) - Participants with EBV+ PTLD following SOT that has failed both rituximab and chemotherapy will receive IV tabelecleucel.

Experimental: Cohort HCT (C-HCT) - Participants with EBV+ PTLD following HCT that has failed rituximab containing regimen will receive IV tabelecleucel.


Treatment: Other: tabelecleucel
Tabelecleucel is being investigated as an off-the-shelf, allogeneic T-cell immunotherapy for the treatment of EBV+ malignancies and diseases.
Intervention code [1] 0 0
Treatment: Other
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Objective response rate (ORR) in the Analysis Cohorts C-SOT, C-HCT, and Combined Population (C-SOT-R+C, C-SOT-R-Ci, and C-HCT) Who Received Commercial Product, or a Product Manufactured Using a Comparable PV
Timepoint [1] 0 0
2 years
Secondary outcome [1] 0 0
Duration of response (DOR) in the Analysis Cohorts C-SOT and C-HCT Separately
Timepoint [1] 0 0
2 years
Secondary outcome [2] 0 0
ORR and DOR in the Analysis Cohorts C-SOT and C-HCT Combined
Timepoint [2] 0 0
2 years
Secondary outcome [3] 0 0
ORR and DOR in Participants who Received Commercial Product or a Product Manufactured Using a Comparable PV in the Analysis Cohorts C-SOT-R-Ci and C-SOT-R+C Separately and Combined, and in the Analysis Cohort C-HCT
Timepoint [3] 0 0
2 years
Secondary outcome [4] 0 0
DOR in the Analysis Cohort of the Combined Population (C-SOT-R+C, C-SOT-R-Ci, and C-HCT) who Received Commercial Product or a Product Manufactured Using a Comparable PV
Timepoint [4] 0 0
2 years
Secondary outcome [5] 0 0
Rates of Complete Response (CR) and Partial Response (PR)
Timepoint [5] 0 0
2 years
Secondary outcome [6] 0 0
Time to Response
Timepoint [6] 0 0
2 years
Secondary outcome [7] 0 0
Time to Best Response
Timepoint [7] 0 0
2 years
Secondary outcome [8] 0 0
Overall Survival (OS)
Timepoint [8] 0 0
2 years
Secondary outcome [9] 0 0
Rates of Allograft Loss or Rejection Episodes (Analysis Cohort C-SOT)
Timepoint [9] 0 0
2 years

Eligibility
Key inclusion criteria
1. Prior SOT of kidney, liver, heart, lung, pancreas, small bowel, or any combination of these (C-SOT); or prior allogeneic HCT (C-HCT)
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 or interchangeable commercially available biosimilar monotherapy (C-SOT-R or C-HCT) or rituximab plus any concurrent or sequentially administered chemotherapy regimen (C-SOT-R+C) for treatment of PTLD.
6. Males and females of any age.
7. Eastern Cooperative Oncology Group performance status = 3 for subjects aged = 16 years; Lansky score = 20 for subjects < 16 years
8. For C-HCT 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
9. Adequate organ function

1. Absolute neutrophil count = 1000/µL, (C-SOT) or = 500/µL (C-HCT), with or without cytokine support
2. Platelet count = 50,000/µL, with or without transfusion or cytokine support. For C-HCT, 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)
3. 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
10. Subject or subject's representative is willing and able to provide written informed consent
Minimum age
No limit
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
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.
4. 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
5. 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
6. For C-HCT: active adenovirus viremia
7. Need for vasopressor or ventilatory support
8. Antithymocyte globulin or similar anti-T cell antibody therapy = 4 weeks prior to enrollment
9. Treatment with Epstein-Barr virus cytotoxic T lymphocytes or chimeric antigen receptor T cells directed against B cells within 8 weeks of enrollment (C-SOT or C-HCT), or unselected donor lymphocyte infusion within 8 weeks of enrollment (C-HCT only)
10. 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
11. Inability to comply with study-related procedures
12. Any medical condition or organ system dysfunction that in the investigator's opinion, could compromise the participant's safety or ability to complete the study

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
29/12/2017
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/06/2027
Actual
Sample size
Target
66
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC,WA
Recruitment hospital [1] 0 0
The Children's Hospital at Westmead (Pediatrics only) - Westmead
Recruitment hospital [2] 0 0
Westmead Hospital (Adults only) - Westmead
Recruitment hospital [3] 0 0
The Prince Charles Hospital (Adults only) - Chermside
Recruitment hospital [4] 0 0
Royal Adelaide Hospital (Adults only) - Adelaide
Recruitment hospital [5] 0 0
The Royal Children's Hospital Melbourne (Pediatrics only) - Melbourne
Recruitment hospital [6] 0 0
Fiona Stanley Hospital (Adults only) - Murdoch
Recruitment postcode(s) [1] 0 0
2145 - Westmead
Recruitment postcode(s) [2] 0 0
4032 - Chermside
Recruitment postcode(s) [3] 0 0
5000 - Adelaide
Recruitment postcode(s) [4] 0 0
3052 - Melbourne
Recruitment postcode(s) [5] 0 0
6150 - Murdoch
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Connecticut
Country [3] 0 0
United States of America
State/province [3] 0 0
District of Columbia
Country [4] 0 0
United States of America
State/province [4] 0 0
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Georgia
Country [6] 0 0
United States of America
State/province [6] 0 0
Illinois
Country [7] 0 0
United States of America
State/province [7] 0 0
Maryland
Country [8] 0 0
United States of America
State/province [8] 0 0
Massachusetts
Country [9] 0 0
United States of America
State/province [9] 0 0
Missouri
Country [10] 0 0
United States of America
State/province [10] 0 0
New York
Country [11] 0 0
United States of America
State/province [11] 0 0
North Carolina
Country [12] 0 0
United States of America
State/province [12] 0 0
Ohio
Country [13] 0 0
United States of America
State/province [13] 0 0
Oregon
Country [14] 0 0
United States of America
State/province [14] 0 0
Pennsylvania
Country [15] 0 0
United States of America
State/province [15] 0 0
South Carolina
Country [16] 0 0
United States of America
State/province [16] 0 0
Tennessee
Country [17] 0 0
United States of America
State/province [17] 0 0
Texas
Country [18] 0 0
United States of America
State/province [18] 0 0
Wisconsin
Country [19] 0 0
Austria
State/province [19] 0 0
Wien
Country [20] 0 0
Belgium
State/province [20] 0 0
Brussels
Country [21] 0 0
Belgium
State/province [21] 0 0
Flemish Brabant
Country [22] 0 0
Canada
State/province [22] 0 0
Alberta
Country [23] 0 0
Canada
State/province [23] 0 0
Ontario
Country [24] 0 0
France
State/province [24] 0 0
Aquitaine
Country [25] 0 0
France
State/province [25] 0 0
Ile-de-France
Country [26] 0 0
France
State/province [26] 0 0
Nord-Pas-de-Calais
Country [27] 0 0
France
State/province [27] 0 0
Île-de-France
Country [28] 0 0
Italy
State/province [28] 0 0
Milano
Country [29] 0 0
Italy
State/province [29] 0 0
Pavia
Country [30] 0 0
Italy
State/province [30] 0 0
Roma
Country [31] 0 0
Italy
State/province [31] 0 0
Torino
Country [32] 0 0
Spain
State/province [32] 0 0
Barcelona
Country [33] 0 0
Spain
State/province [33] 0 0
Cantabria
Country [34] 0 0
Spain
State/province [34] 0 0
Madrid
Country [35] 0 0
Spain
State/province [35] 0 0
Sevilla
Country [36] 0 0
Spain
State/province [36] 0 0
Valencia
Country [37] 0 0
United Kingdom
State/province [37] 0 0
England

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Atara Biotherapeutics
Address
Country

Ethics approval
Ethics application status

Summary
Brief 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 (SOT-R) and rituximab plus chemotherapy (SOT-R+C) or (2) allogeneic hematopoietic cell transplant (HCT) after failure of rituximab.
Trial website
https://clinicaltrials.gov/study/NCT03394365
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Aditi Mehta, DO
Address 0 0
Atara Biotherapeutics
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Aditi Mehta, DO
Address 0 0
Country 0 0
Phone 0 0
650-278-8930
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT03394365