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
- Registration Number
- NCT03394365
- Lead Sponsor
- Atara Biotherapeutics
- 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) al...
- Detailed Description
This is a multicenter, open-label, phase 3 study to assess the efficacy and safety of tabelecleucel for the treatment of EBV+ PTLD in the setting of SOT-R and SOT-R+C (Cohort \[C\]-SOT) or HCT after failure of rituximab (C-HCT).
SOT-R further included participants:
...
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 66
-
Prior SOT of kidney, liver, heart, lung, pancreas, small bowel, or any combination of these (C-SOT); or prior allogeneic HCT (C-HCT)
-
A diagnosis of locally assessed, biopsy-proven EBV+ PTLD
-
Availability of appropriate partially HLA-matched and restricted tabelecleucel has been confirmed by the sponsor
-
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.
-
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.
-
Males and females of any age.
-
Eastern Cooperative Oncology Group performance status ≤ 3 for subjects aged ≥ 16 years; Lansky score ≥ 20 for subjects < 16 years
-
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
-
Adequate organ function
- Absolute neutrophil count ≥ 1000/μL, (C-SOT) or ≥ 500/μL (C-HCT), with or without cytokine support
- 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)
- 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
-
Subject or subject's representative is willing and able to provide written informed consent
- Burkitt lymphoma, classical Hodgkin lymphoma, or any T cell lymphoma
- Daily steroids of > 0.5 mg/kg prednisone or glucocorticoid equivalent, ongoing methotrexate, or extracorporeal photopheresis
- 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.
- 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
- 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
- For C-HCT: active adenovirus viremia
- Need for vasopressor or ventilatory support
- Antithymocyte globulin or similar anti-T cell antibody therapy ≤ 4 weeks prior to enrollment
- 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)
- 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
- Inability to comply with study-related procedures
- 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
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Cohort SOT-R (C-SOT-R) tabelecleucel Participants with EBV+ PTLD following SOT that has failed rituximab will receive IV tabelecleucel. Cohort SOT-R+C (C-SOT-R+C) tabelecleucel Participants with EBV+ PTLD following SOT that has failed both rituximab and chemotherapy will receive IV tabelecleucel. Cohort HCT (C-HCT) tabelecleucel Participants with EBV+ PTLD following HCT that has failed rituximab containing regimen will receive IV tabelecleucel.
- Primary Outcome Measures
Name Time Method 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 2 years
- Secondary Outcome Measures
Name Time Method Duration of response (DOR) in the Analysis Cohorts C-SOT and C-HCT Separately 2 years ORR and DOR in the Analysis Cohorts C-SOT and C-HCT Combined 2 years 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 2 years 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 2 years Rates of Complete Response (CR) and Partial Response (PR) 2 years Time to Response 2 years Time to Best Response 2 years Overall Survival (OS) 2 years Rates of Allograft Loss or Rejection Episodes (Analysis Cohort C-SOT) 2 years
Trial Locations
- Locations (71)
University of Maryland School of Medicine (Adults only)
🇺🇸Baltimore, Maryland, United States
Arthur M. Blank Hospital (Pediatrics)
🇺🇸Atlanta, Georgia, United States
City of Hope (Adults and Pediatrics)
🇺🇸Duarte, California, United States
University of California San Diego Moores Cancer Center (Adults only)
🇺🇸La Jolla, California, United States
Loma Linda University Medical Center (Adults only)
🇺🇸Loma Linda, California, United States
Children's Hospital Los Angeles, Div. of Research Immunology/BMT (Adults and Pediatrics)
🇺🇸Los Angeles, California, United States
UCLA Medical Center (Adults and Pediatrics)
🇺🇸Los Angeles, California, United States
University of California Davis Comprehensive Cancer Center (Adults only)
🇺🇸Sacramento, California, United States
Yale University (Adults and Pediatrics)
🇺🇸New Haven, Connecticut, United States
MedStar Georgetown University Hospital (Adults and Pediatrics)
🇺🇸Washington, District of Columbia, United States
University of Florida (Adults and Pediatrics)
🇺🇸Gainesville, Florida, United States
University of Miami/Jackson Memorial Hospital (Adults only)
🇺🇸Miami, Florida, United States
Winship Cancer Institute (Adults only)
🇺🇸Atlanta, Georgia, United States
Ann & Robert H. Lurie Children's Hospital of Chicago (Adults and Pediatrics)
🇺🇸Chicago, Illinois, United States
University of Chicago Medical Center - Duchossois Center for Advanced Medicine (Adults only)
🇺🇸Chicago, Illinois, United States
Loyola University Medical Center (Adults and Pediatrics)
🇺🇸Maywood, Illinois, United States
Dana Farber Cancer Institute, Brigham and Women's Hospital (Adults and Pediatrics)
🇺🇸Boston, Massachusetts, United States
Washington University School of Medicine (Adults only)
🇺🇸Saint Louis, Missouri, United States
Montefiore Medical Center (Adults only)
🇺🇸Bronx, New York, United States
Montefiore Medical Center (Pediatrics only)
🇺🇸Bronx, New York, United States
Weill Cornell Medicine (Adults only)
🇺🇸New York, New York, United States
Columbia University Medical Center (Adults and Pediatrics)
🇺🇸New York, New York, United States
Memorial Sloan Kettering Cancer Center (Adults and Pediatrics)
🇺🇸New York, New York, United States
University of North Carolina at Chapel Hill, Lineberger Comprehensive Cancer Center (Adults and Pediatrics)
🇺🇸Chapel Hill, North Carolina, United States
Carolinas Medical Center/Levine Children's Hospital (Adults and Pediatrics)
🇺🇸Charlotte, North Carolina, United States
Duke Cancer Institute (Adults only)
🇺🇸Durham, North Carolina, United States
Cleveland Clinic Foundation (Adults and Pediatrics)
🇺🇸Cleveland, Ohio, United States
Nationwide Children's Hospital (Pediatrics only)
🇺🇸Columbus, Ohio, United States
Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (Adults and Pediatrics)
🇺🇸Columbus, Ohio, United States
Oregon Health and Science University Physicians Pavilion (Adults and Pediatrics)
🇺🇸Portland, Oregon, United States
Hospital of the University of Pennsylvania (Adults only)
🇺🇸Philadelphia, Pennsylvania, United States
The Children's Hospital of Philadelphia Oncology Division, Blood & Marrow Transplant Section (Pediatrics)
🇺🇸Philadelphia, Pennsylvania, United States
University of Pittsburgh Medical Center (Adults only)
🇺🇸Pittsburgh, Pennsylvania, United States
Medical University of South Carolina (Adults and Pediatrics)
🇺🇸Charleston, South Carolina, United States
Saint Jude Children's Research Hospital (Pediatrics only)
🇺🇸Memphis, Tennessee, United States
Vanderbilt University Medical Center Henry-Joyce Cancer Clinic (Adults and Pediatrics)
🇺🇸Nashville, Tennessee, 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
MD Anderson Cancer Center (Pediatrics and Adult)
🇺🇸Houston, Texas, United States
Froedtert and Medical College of Wisconsin - Clinical Cancer Center (Adults only)
🇺🇸Milwaukee, Wisconsin, United States
The Children's Hospital at Westmead (Pediatrics only)
🇦🇺Westmead, New South Wales, Australia
Westmead Hospital (Adults only)
🇦🇺Westmead, New South Wales, Australia
The Prince Charles Hospital (Adults only)
🇦🇺Chermside, Queensland, Australia
Royal Adelaide Hospital (Adults only)
🇦🇺Adelaide, South Australia, Australia
The Royal Children's Hospital Melbourne (Pediatrics only)
🇦🇺Melbourne, Victoria, Australia
Fiona Stanley Hospital (Adults only)
🇦🇺Murdoch, Western Australia, Australia
Medizinische Universitat Wien (Adults only)
🇦🇹Wien, Austria
Centre Hospitalier Universitaire de Liège Site Sart Tilman (Adults and Pediatrics)
🇧🇪Liège, Brussels, Belgium
Universitair Ziekenhuis Leuven (Adults and Pediatrics)
🇧🇪Leuven, Flemish Brabant, Belgium
Alberta Children's Hospital (Adults and Pediatrics)
🇨🇦Calgary, Alberta, Canada
Sick Kids (Pediatrics only)
🇨🇦Toronto, Ontario, Canada
Princess Margaret Cancer Centre (Adults only)
🇨🇦Toronto, Ontario, Canada
Centre Hospitalier Universitaire de Bordeaux (Adults only)
🇫🇷Pessac, Aquitaine, France
Hôpital Saint Antoine (Adults only)
🇫🇷Paris, Ile-de-France, France
Centre Hospitalier Régional Universitaire de Lille (Adults and Pediatrics)
🇫🇷Lille cedex, Nord-Pas-de-Calais, France
Hôpital Necker-Enfants Malades (Pediatrics only)
🇫🇷Paris 15, Île-de-France, France
Hôpital Universitaire Pitié Salpêtrière (Adults only)
🇫🇷Paris Cedex 13, Île-de-France, France
Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda (Adults only)
🇮🇹Milano, Italy
Fondazione IRCCS Policlinico San Matteo (Adults and Pediatrics)
🇮🇹Pavia, Italy
Fondazione Policlinico Universitario Agostino Gemelli (Adults only)
🇮🇹Roma, Italy
Ospedale Pediatrico Bambino Gesu (Pediatrics only)
🇮🇹Roma, Italy
Azienda Ospedaliera - Universitaria Città della Salute e della Scienza di Torino (Adults only)
🇮🇹Torino, Italy
Hospital Duran i Reynals (Adults and Pediatrics)
🇪🇸Badalona, Barcelona, Spain
Hospital Universitario Marqués de Valdecilla (Adults and Pediatrics)
🇪🇸Santander, Cantabria, Spain
Hospital Universitari Vall d'Hebrón - Institut de Recerca (Adults and Pediatrics)
🇪🇸Barcelona, Spain
Hospital General Universitario Gregorio Marañón (Adults and Pediatrics)
🇪🇸Madrid, Spain
University Hospital Virgen del Rocio (Adults and Pediatrics)
🇪🇸Sevilla, Spain
Hospital Universitario La Fe (Adults and Pediatrics)
🇪🇸Valencia, Spain
University Hospitals Birmingham NHS Foundation Trust (Adults only)
🇬🇧Birmingham, England, United Kingdom
King's College Hospital NHS Foundation Trust (Adults only)
🇬🇧London, England, United Kingdom
Imperial College Healthcare NHS Trust (Adults only)
🇬🇧London, England, United Kingdom