A Phase 3 Study of Tabelecleucel for Participants With Epstein-Barr Virus-Associated Post-Transplant Lymphoproliferative Disease After Failure With Rituximab or Rituximab and Chemotherapy
Recruiting · NCT03394365 · Interventional (participants receive a specific treatment) · Lead sponsor: Pierre Fabre Medicament
View the official record on ClinicalTrials.gov →Interventions studied
tabelecleucel
What this trial is about
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) allogeneic hematopoietic cell transplant (HCT) after failure of rituximab.
Who can take part
Age range
No age limits stated
Sex
All (male and female)
Healthy volunteers
No - a diagnosis or condition is required
Phase
Phase 3
Study type
Interventional (participants receive a specific treatment)
Inclusion criteria
- 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 participants 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 participants aged ≥ 16 years; Lansky score ≥ 20 for participants \< 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 participant 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 participant 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.
- Participant or participant's representative is willing and able to provide written informed consent.
Exclusion criteria
- Currently active Burkitt, T-cell, NK/T-cell lymphoma/LPD, Hodgkin, plasmablastic, transformed lymphoma, active hemophagocytic lymphohistiocytosis, or other malignancies requiring systemic therapy.
- 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 participant is actively receiving CNS-directed chemotherapy (systemic or intrathecal) or radiotherapy at enrollment. NOTE: Participants 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.
Where it is running
60 locations listed across 18 US 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 D.C., 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
- Arthur M Blank Hospital - Children's Healthcare of Atlanta - 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
- 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
- Washington University School of Medicine (Adults only) - St Louis, Missouri, 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
- Montefiore Medical Center (Adults only) - The Bronx, New York, United States
- Montefiore Medical Center (Pediatrics only) - The Bronx, 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 and Pediatrics) - 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
- Alberta Children's Hospital (Adults and Pediatrics) - Calgary, Alberta, Canada
- Centre Hospitalier Universitaire de Bordeaux (Adults only) - Pessac, Aquitaine, France
- Medizinische Universitat Wien (Adults only) - Vienna, Austria, Austria
- Hospital Duran i Reynals (Adults and Pediatrics) - Badalona, BARCELONA, Spain
- Hospital Universitari Vall d'Hebrón - Institut de Recerca (Adults and Pediatrics) - Barcelona, Barcelona, Spain
- Centre Hospitalier Universitaire de Liège Site Sart Tilman (Adults and Pediatrics) - Liège, Brussels Capital, Belgium
- Hospital Universitario Marqués de Valdecilla (Adults and Pediatrics) - Santander, Cantabria, 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
- Universitair Ziekenhuis Leuven (Adults and Pediatrics) - Leuven, Flemish Brabant, Belgium
- Centre Hospitalier Régional Universitaire de Lille (Adults and Pediatrics) - Lille, Hauts-de-France, France
- Hospital General Universitario Gregorio Marañón (Adults and Pediatrics) - Madrid, Madrid, Spain
- Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda (Adults only) - Milan, Milano, Italy
- The Children's Hospital at Westmead (Pediatrics only) - Westmead, New South Wales, Australia
- Westmead Hospital (Adults only) - Westmead, New South Wales, Australia
- Sick Kids (Pediatrics only) - Toronto, Ontario, Canada
- Princess Margaret Cancer Centre (Adults only) - Toronto, Ontario, Canada
- Fondazione IRCCS Policlinico San Matteo (Adults and Pediatrics) - Pavia, Pavia, Italy
- The Prince Charles Hospital (Adults only) - Chermside, Queensland, Australia
Showing 60 of 71 listed sites. See the official record for the complete list.
Read the full protocol, contacts and eligibility on ClinicalTrials.gov →