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

Stem Cell Transplant Complications Clinical Trial

— MATCH  

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 Details — Status: Completed

Administrative data

• NCT number: NCT03392142
• Other study ID #: ATA129-EBV-301
• Status: Completed
• Phase: Phase 3
• Start date: December 29, 2017
• Est. completion date: February 16, 2021

Study information

• Verified date: March 2021
• Source: Atara Biotherapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 8
• Est. completion date: February 16, 2021
• Est. primary completion date: February 16, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

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

Related Conditions & MeSH terms

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

Intervention

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

Locations

Country	Name	City	State
Australia	Royal Adelaide Hospital (Adults only)	Adelaide	South Australia
Australia	Fiona Stanley Hospital (Adults only)	Murdoch	Western Australia
Australia	The Royal Melbourne Hospital or The Peter MacCallum Cancer Centre (Adults only)	Parkville	Victoria
Australia	Westmead Hospital (Adults only)	Westmead	New South Wales
United States	Winship Cancer Institute of Emory University (Adults only)	Atlanta	Georgia
United States	Children's Hospital of Colorado (Pediatrics Only)	Aurora	Colorado
United States	University of Maryland School of Medicine (Adults Only)	Baltimore	Maryland
United States	Dana Farber Cancer Institute, Brigham and Women's Hospital (Adults and Pediatrics)	Boston	Massachusetts
United States	Montefiore Medical Center (Pediatrics only)	Bronx	New York
United States	UNC Hospitals (Adults and Pediatrics)	Chapel Hill	North Carolina
United States	Medical University of South Carolina (Adults and Pediatrics)	Charleston	South Carolina
United States	Carolinas Medical Center/Levine Children's Hospital (Adults and Pediatrics)	Charlotte	North Carolina
United States	Ann & Robert H. Lurie Children's Hospital of Chicago Research Center (Adults and Pediatrics)	Chicago	Illinois
United States	Baylor Scott and White Research Institute (Adults Only)	Dallas	Texas
United States	University of Texas Southwestern Medical Center - Children's Medical Center (Pediatrics only)	Dallas	Texas
United States	University of Texas MD Anderson Cancer Center (Adults and Pediatrics)	Houston	Texas
United States	University of California San Diego Moores Cancer Center (Adults Only)	La Jolla	California
United States	Loyola University Medical Center (Adults and Pediatrics)	Maywood	Illinois
United States	St. Jude Children's Research Hospital (Pediatrics only)	Memphis	Tennessee
United States	University of Miami/Jackson Memorial Hospital (Adults only)	Miami	Florida
United States	Vanderbilt - Ingram Cancer Center (Adults and Pediatrics)	Nashville	Tennessee
United States	Memorial Sloan Kettering Cancer Center (Adults and Pediatrics)	New York	New York
United States	New York-Presbyterian Columbia University Medical Center (Adults and Pediatrics)	New York	New York
United States	Weill Cornell Medical College (Adults only)	New York	New York
United States	Oregon Health and Science University (Adults and Pediatrics)	Portland	Oregon
United States	Washington University School of Medicine (Adults only)	Saint Louis	Missouri
United States	Lombardi Comprehansive Cancer Center (Adults and Pediatrics)	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Atara Biotherapeutics

Countries where clinical trial is conducted

United States,  Australia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective response rate (ORR)		2 years
Secondary	Overall survival (OS)		5 years
Secondary	Duration of response (DOR)		2 years
Secondary	PTLD progression-free survival (PFS) following best response		2 years
Secondary	Rate of durable response		2 years
Secondary	Time to progression		2 years
Secondary	Patient reported outcome: EQ-5D		2 years
Secondary	Patient reported outcome: Functional Assessment of Cancer Therapy Lymphoma (FACT-Lym)		2 years
Secondary	Incidence of related and unrelated adverse events (AE), including AEs of special interest		2 years