Tabelecleucel for Allogeneic Hematopoietic Cell Transplant Subjects With Epstein-Barr Virus-Associated Post-Transplant Lymphoproliferative Disease (EBV+ PTLD) After Failure of Rituximab (MATCH)

• ClinicalTrials.gov Identifier: NCT03392142
• Recruitment Status: Completed
• First Posted: January 5, 2018
• Last Update Posted: March 26, 2021
• Sponsor: Atara Biotherapeutics
• Information provided by (Responsible Party): Atara Biotherapeutics

Tracking Information

• First Submitted Date: December 29, 2017
• First Posted Date: January 5, 2018
• Last Update Posted Date: March 26, 2021
• Actual Study Start Date: December 29, 2017
• Actual Primary Completion Date: February 16, 2021 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: January 4, 2018): Objective response rate (ORR) [ Time Frame: 2 years ]
• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: April 10, 2018)

• Overall survival (OS) [ Time Frame: 5 years ]
• Duration of response (DOR) [ Time Frame: 2 years ]
• PTLD progression-free survival (PFS) following best response [ Time Frame: 2 years ]
• Rate of durable response [ Time Frame: 2 years ]
• Time to progression [ Time Frame: 2 years ]
• Patient reported outcome: EQ-5D [ Time Frame: 2 years ]
• Patient reported outcome: Functional Assessment of Cancer Therapy Lymphoma (FACT-Lym) [ Time Frame: 2 years ]
• Incidence of related and unrelated adverse events (AE), including AEs of special interest [ Time Frame: 2 years ]

Original Secondary Outcome Measures (submitted: January 4, 2018)

• Overall survival (OS) [ Time Frame: 5 years ]
• Incidence of related and unrelated adverse events (AE), including AEs of interest [ Time Frame: 2 years ]
• Patient reported outcome: EQ-5D [ Time Frame: 2 years ]
• Patient reported outcome: Functional Assessment of Cancer Therapy Lymphoma (FACT-Lym) [ Time Frame: 2 years ]
• Duration of response (DOR) [ Time Frame: 2 years ]
• Rate of durable response [ Time Frame: 2 years ]
• PTLD progression-free survival (PFS) following best response [ Time Frame: 2 years ]
• Time to progression [ Time Frame: 2 years ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• 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
• Brief Summary: 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).

• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Epstein-Barr Virus-Associated Post-Transplant Lymphoproliferative Disease (EBV+ PTLD)
• Stem Cell Transplant Complications
• Lymphoproliferative Disorders

Intervention

Biological: tabelecleucel

Tabelecleucel is being investigated as an off-the-shelf, allogeneic T-cell immunotherapy for the treatment of EBV+ malignancies and diseases.

Other Names:

• tab-cel®
• ATA129
• EBV-CTL

Study Arms

Experimental: tabelecleucel

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.

Intervention: Biological: tabelecleucel

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: March 24, 2021): 8
• Original Estimated Enrollment (submitted: January 4, 2018): 33
• Actual Study Completion Date: February 16, 2021
• Actual Primary Completion Date: February 16, 2021 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: Child, Adult, Older Adult
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, United States

Administrative Information

• NCT Number: NCT03392142
• Other Study ID Numbers: ATA129-EBV-301
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Responsible Party: Atara Biotherapeutics
• Study Sponsor: Atara Biotherapeutics
• Collaborators: Not Provided

Investigators

• Study Director: Willis Navarro, MD; Atara Biotherapeutics

• PRS Account: Atara Biotherapeutics
• Verification Date: March 2021