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Trial details imported from ClinicalTrials.gov

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




Registration number
NCT03394365
Ethics application status
Date submitted
29/12/2017
Date registered
9/01/2018
Date last updated
29/06/2020

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
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(has expanded access)
Description of intervention(s) / exposure
Other interventions - tabelecleucel

Experimental: SOT cohort -Subgroup A - Participants who have failed rituximab will receive IV tabelecleucel.

Experimental: SOT cohort -Subgroup B - Participants who have failed both rituximab and chemotherapy will receive IV tabelecleucel.

Experimental: HCT cohort - Participants who have failed rituximab will receive IV tabelecleucel.


Other interventions: 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
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Objective response rate (ORR) in the SOT or HCT cohort
Timepoint [1] 0 0
2 years
Secondary outcome [1] 0 0
Duration of response (DOR) in SOT and HCT cohorts separately
Timepoint [1] 0 0
2 years
Secondary outcome [2] 0 0
ORR and DOR in SOT and HCT cohorts combined
Timepoint [2] 0 0
2 years
Secondary outcome [3] 0 0
Rates of complete response (CR) and partial response (PR)
Timepoint [3] 0 0
2 years
Secondary outcome [4] 0 0
Time to response
Timepoint [4] 0 0
2 years
Secondary outcome [5] 0 0
Time to best response
Timepoint [5] 0 0
2 years
Secondary outcome [6] 0 0
Overall survival (OS)
Timepoint [6] 0 0
2 years
Secondary outcome [7] 0 0
Rates of allograft loss or rejection episodes (SOT cohort)
Timepoint [7] 0 0
2 years

Eligibility
Key inclusion criteria
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

1. Absolute neutrophil count = 1000/µL, (SOT cohort) or = 500/µL (HCT cohort), with
or without cytokine support

2. 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)

3. 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).

9. Subject or subject's representative is willing and able to provide written informed
consent
Minimum age
No limit
Maximum age
No limit
Gender
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 (CIBMTR) 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 HCT cohort: 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
(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)

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

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
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,WA
Recruitment hospital [1] 0 0
Westmead Hospital (Adults only) - Westmead
Recruitment hospital [2] 0 0
Prince Charles Hospital (Adults only) - Chermside
Recruitment hospital [3] 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
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
Spain
State/province [19] 0 0
Sevilla

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 and rituximab plus chemotherapy or (2) allogeneic hematopoietic
cell transplant (HCT) after failure of rituximab.
Trial website
https://clinicaltrials.gov/show/NCT03394365
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Minoti Hiremath, MBBS, PhD
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
Minoti Hiremath, MBBS, PhD
Address 0 0
Country 0 0
Phone 0 0
805-796-4080
Fax 0 0
Email 0 0
clinicalstudies@atarabio.com
Contact person for scientific queries

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