Description:
This is a multicenter, open label, single-arm, phase 3 study to assess the efficacy and
safety of tabelecleucel for the treatment of Epstein-Barr virus-associated post-transplant
lymphoproliferative disease (EBV+ PTLD) in the setting of allogeneic hematopoietic cell
transplant (HCT) after failure of rituximab.
Title
- Brief Title: Tabelecleucel for Allogeneic Hematopoietic Cell Transplant Subjects With Epstein-Barr Virus-Associated Post-Transplant Lymphoproliferative Disease (EBV+ PTLD) After Failure of Rituximab
- Official Title: Multicenter, Open-Label, Phase 3 Study of Tabelecleucel for Allogeneic Hematopoietic Cell Transplant Subjects With Epstein-Barr Virus-Associated Post-Transplant Lymphoproliferative Disease After Failure of Rituximab
Clinical Trial IDs
- ORG STUDY ID:
ATA129-EBV-301
- NCT ID:
NCT03392142
Conditions
- Epstein-Barr Virus-Associated Post-Transplant Lymphoproliferative Disease (EBV+ PTLD)
- Stem Cell Transplant Complications
- Lymphoproliferative Disorders
Interventions
Drug | Synonyms | Arms |
---|
tabelecleucel | tab-cel®, ATA129, EBV-CTL | tabelecleucel |
Purpose
This is a multicenter, open label, single-arm, phase 3 study to assess the efficacy and
safety of tabelecleucel for the treatment of Epstein-Barr virus-associated post-transplant
lymphoproliferative disease (EBV+ PTLD) in the setting of allogeneic hematopoietic cell
transplant (HCT) after failure of rituximab.
Detailed Description
This is a multicenter, open label, single-arm, phase 3 study to assess the efficacy and
safety of tabelecleucel for the treatment of EBV+ PTLD in the setting of allogeneic HCT after
failure of rituximab.
Tabelecleucel will be selected for the subject from the bank of available tabelecleucel cell
products based on matching >= 2 human leukocyte antigen (HLA) alleles, at least one of which
is a restricting HLA allele, shared between the tabelecleucel donor and the subject's EBV+
PTLD. Sites will provide high resolution subject and subject's graft donor HLA typing results
and other information as required by the protocol.
Tabelecleucel will be administered in cycles lasting 5 weeks (35 days). During each cycle,
subjects will receive intravenous (IV) tabelecleucel at a dose of 2×10^6 cells/kg on Days 1,
8, and 15, followed by observation through Day 35.
NOTE, 29 April 2020: Study sites/locations with status "completed" may be screening EBV+ PTLD
HCT subjects in clinical study ATA129-EBV-302 (NCT03394365).
NOTE, 16 February 2021: all study sites have closed and all data has been transferred to the
clinical study database for monitoring under ATA129-EBV-302 (NCT03394365).
Trial Arms
Name | Type | Description | Interventions |
---|
tabelecleucel | Experimental | Tabelecleucel will be administered in cycles lasting 5 weeks (35 days). During each cycle, subjects will receive intravenous (IV) tabelecleucel at a dose of 2 x 10^6 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 multiple tabelecleucel cell products. | |
Eligibility Criteria
Inclusion Criteria:
1. Prior allogeneic hematopoietic cell transplant
2. A diagnosis of locally-assessed, biopsy-proven EBV+ PTLD with a pathology sample
available for central review
3. Availability of appropriate partially HLA-matched and restricted tabelecleucel cell
product
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). Baseline scans must be of acceptable
quality to the central radiology laboratory prior to Cycle 1 Day 1.
5. Failure of rituximab for first-line treatment of PTLD. Note: Subjects with CD20
negative disease are eligible to enroll without prior anti-CD20 therapy after failure
of first-line treatment (reduction of immunosuppression is not considered first-line
therapy) and discussion with the sponsor's medical monitor.
6. Males and females of any age
7. Eastern Cooperative Oncology Group (ECOG) performance status <= 3 for subjects aged >
16 years; Lansky score >= 20 for subjects from birth to 16 years
8. Underlying primary disease, for which the subject underwent transplant, is in
morphologic remission
9. Adequate organ function
1. Absolute neutrophil count >= 500/µL, with or without cytokine support
2. Platelet count >= 50,000/µL, with or without transfusion support; 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 6 months (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 < 3 x the upper limit of normal (ULN); however, ALT, AST,
and TBILI each <= 5 x ULN is acceptable if the elevation is considered by the
investigator to be due to PTLD involvement of the liver
4. Creatinine < 3 x ULN
10. Subject or subject's representative is willing and able to provide written informed
consent
Exclusion Criteria:
1. Daily steroids of > 0.5 mg/kg prednisone or glucocorticoid equivalent, methotrexate,
or extracorporeal photopheresis
2. History of central nervous system (CNS) PTLD
3. Grade >= 2 graft-versus-host disease (GvHD) per the Center for International Blood and
Marrow Transplant Research (CIBMTR) consensus grading system at enrollment
4. Ongoing or recent use of a checkpoint inhibitor (eg, nivolumab, pembrolizumab,
ipilimumab) within three drug half-lives from the most recent dose to Cycle 1 Day 1
5. Active adenovirus viremia
6. Need for vasopressor or ventilatory support
7. Antithymocyte globulin or similar anti-T cell antibody therapy <= 4 weeks prior to
Cycle 1 Day 1
8. Treatment with Epstein-Barr virus cytotoxic T lymphocytes, chimeric antigen receptor
(CAR)-T cells directed against B cells, or unselected donor lymphocyte infusion (DLI)
within 8 weeks of Cycle 1 Day 1
9. Pregnancy
10. 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
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: | 5 years |
Safety Issue: | |
Description: | |
Measure: | Duration of response (DOR) |
Time Frame: | 2 years |
Safety Issue: | |
Description: | |
Measure: | PTLD progression-free survival (PFS) following best response |
Time Frame: | 2 years |
Safety Issue: | |
Description: | |
Measure: | Rate of durable response |
Time Frame: | 2 years |
Safety Issue: | |
Description: | |
Measure: | Time to progression |
Time Frame: | 2 years |
Safety Issue: | |
Description: | |
Measure: | Patient reported outcome: EQ-5D |
Time Frame: | 2 years |
Safety Issue: | |
Description: | |
Measure: | Patient reported outcome: Functional Assessment of Cancer Therapy Lymphoma (FACT-Lym) |
Time Frame: | 2 years |
Safety Issue: | |
Description: | |
Measure: | Incidence of related and unrelated adverse events (AE), including AEs of special interest |
Time Frame: | 2 years |
Safety Issue: | |
Description: | |
Details
Phase: | Phase 3 |
Primary Purpose: | Interventional |
Overall Status: | Completed |
Lead Sponsor: | Atara Biotherapeutics |
Trial Keywords
- Epstein-Barr Virus (EBV)-associated Lymphoproliferative Disease (LPD)
- Hematopoietic Cell Transplantation (HCT)
- Hematopoietic Stem Cell Transplantation (HSCT)
- Allogeneic Hematopoietic Cell Transplant
- Bone Marrow Transplant Complications
- Cancer After Transplant
- Cytotoxic T lymphocyte (CTL)
- Epstein-Barr Virus-specific Cytotoxic T Lymphocytes (EBV-CTL)
- Allogeneic, Off-The-Shelf T-cell Immunotherapy
- Post-transplant Lymphoma
- Epstein-Barr Virus (EBV)
Last Updated
March 26, 2021