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 (ALLELE)
Epstein-Barr Virus+ Associated Post-transplant Lymphoproliferative Disease (EBV+ PTLD), Solid Organ Transplant Complications, Lymphoproliferative Disorders
About this trial
This is an interventional treatment trial for Epstein-Barr Virus+ Associated Post-transplant Lymphoproliferative Disease (EBV+ PTLD) focused on measuring Epstein-Barr Virus (EBV)-associated Lymphoproliferative Disease (LPD), Epstein-Barr Virus (EBV), Cytotoxic T lymphocyte (CTL), Cancer After Transplant, Kidney transplant, Renal transplant, Liver transplant, Heart transplant, Lung transplant, Intestinal transplant, Pancreas transplant, Post-transplant Lymphoma, Solid Organ Transplant (SOT), Bone Marrow Transplant Complications, Epstein-Barr Virus-specific Cytotoxic T Lymphocytes (EBV-CTL), Hematopoietic Cell Transplant (HCT), Hematopoietic Stem Cell Transplantation (HSCT), Allogeneic Hematopoietic Cell Transplant, Allogeneic, Off-The-Shelf T-cell Immunotherapy
Eligibility Criteria
Inclusion Criteria:
- Prior SOT of kidney, liver, heart, lung, pancreas, small bowel, or any combination of these (SOT cohort); or prior allogeneic HCT (HCT cohort)
- 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 (SOT subgroup A or HCT cohort) or rituximab plus any concurrent or sequentially administered chemotherapy regimen (SOT subgroup B) for treatment of PTLD.
- Eastern Cooperative Oncology Group performance status ≤ 3 for subjects aged ≥ 16 years; Lansky score ≥ 20 for subjects < 16 years
- For HCT cohort 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, (SOT cohort) or ≥ 500/μL (HCT cohort), with or without cytokine support
- Platelet count ≥ 50,000/μL, with or without transfusion or cytokine support. For HCT cohort, 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
Exclusion Criteria:
- 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 HCT cohort: 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 (SOT or HCT cohorts), or unselected donor lymphocyte infusion within 8 weeks of enrollment (HCT cohort 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
Sites / Locations
- City of Hope (Adults and Pediatrics)Recruiting
- University of California San Diego Moores Cancer Center (Adults only)
- Loma Linda University Cancer Center (Adults only)Recruiting
- Children's Hospital Los Angeles, Div. of Research Immunology/BMT (Adults and Pediatrics)Recruiting
- UCLA Medical Center (Adults and Pediatrics)Recruiting
- University of California Davis Comprehensive Cancer Center (Adults only)
- Yale University (Adults and Pediatrics)Recruiting
- MedStar Georgetown University Hospital (Adults and Pediatrics)Recruiting
- University of Florida (Adults and Pediatrics)
- University of Miami/Jackson Memorial Hospital (Adults only)Recruiting
- Children's Healthcare of Atlanta at Egleston (Pediatrics)Recruiting
- Winship Cancer Institute of Emory University (Adults only)Recruiting
- Ann & Robert H. Lurie Children's Hospital of Chicago (Adults and Pediatrics)Recruiting
- University of Chicago Medical Center - Duchossois Center for Advanced Medicine (Adults only)Recruiting
- Loyola University Medical Center (Adults and Pediatrics)Recruiting
- University of Maryland School of Medicine (Adults only)Recruiting
- Dana Farber Cancer Institute, Brigham and Women's Hospital (Adults and Pediatrics)Recruiting
- Washington University School of Medicine (Adults only)Recruiting
- Montefiore Medical Center (Adults only)
- Montefiore Medical Center (Pediatrics only)
- Weill Cornell Medicine (Adults only)Recruiting
- Columbia University Medical Center (Adults and Pediatrics)Recruiting
- Memorial Sloan Kettering Cancer Center (Adults and Pediatrics)Recruiting
- University of North Carolina at Chapel Hill, Lineberger Comprehensive Cancer Center (Adults and Pediatrics)
- Carolinas Medical Center/Levine Children's Hospital (Adults and Pediatrics)Recruiting
- Duke Cancer Institute (Adults only)Recruiting
- Cleveland Clinic Foundation (Adults and Pediatrics)Recruiting
- Nationwide Children's Hospital (Pediatrics only)
- The Ohio State University - Arthur G. James Cancer Center Hospital (Adults and Pediatrics)Recruiting
- Oregon Health and Science University Physicians Pavilion (Adults and Pediatrics)Recruiting
- Children's Hospital of Philadelphia (Pediatrics only)Recruiting
- University of Pennsylvania (Adults only)
- University of Pittsburgh Medical Center (Adults only)
- Medical University of South Carolina (Adults and Pediatrics)Recruiting
- Saint Jude Children's Research Hospital (Pediatrics only)
- Vanderbilt University Medical Center Henry-Joyce Cancer Clinic (Adults and Pediatrics)Recruiting
- Baylor Scott and White Research Institute (Adults only)Recruiting
- University of Texas Southwestern Medical Center - Children's Medical Center (Pediatrics only)Recruiting
- MD Anderson Cancer Center (Adults and Pediatrics)Recruiting
- Froedtert Hospital & the Medical College of Wisconsin (Adults only)
- The Children's Hospital at Westmead (Pediatrics only)Recruiting
- Westmead Hospital (Adults only)Recruiting
- The Prince Charles Hospital (Adults only)Recruiting
- Royal Adelaide Hospital (Adults only)Recruiting
- The Royal Children's Hospital Melbourne (Pediatrics only)Recruiting
- Fiona Stanley Hospital (Adults only)Recruiting
- Medizinische Universitat Wien (Adults only)Recruiting
- Centre Hospitalier Universitaire de Liège Site Sart Tilman (Adults and Pediatrics)Recruiting
- Universitair Ziekenhuis Leuven (Adults and Pediatrics)Recruiting
- Alberta Children's Hospital (Adults and Pediatrics)Recruiting
- Sick Kids (Pediatrics only)Recruiting
- Princess Margaret Cancer Centre (Adults only)Recruiting
- Groupe Hospitalier du Haut Leveque (Adults only)Recruiting
- Hôpital Saint Antoine (Adults only)Recruiting
- Centre Hospitalier Régional Universitaire de Lille (Adults and Pediatrics)Recruiting
- Hôpital Necker-Enfants Malades (Pediatrics only)Recruiting
- Hôpital Universitaire Pitié Salpêtrière (Adults only)Recruiting
- Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda (Adults only)Recruiting
- Fondazione IRCCS Policlinico San Matteo (Adults and Pediatrics)Recruiting
- Fondazione Policlinico Universitario Agostino Gemelli (Adults only)Recruiting
- Ospedale Pediatrico Bambino Gesu (Pediatrics only)Recruiting
- Azienda Ospedaliera - Universitaria Città della Salute e della Scienza di Torino (Adults only)Recruiting
- Hospital Duran i ReynalsRecruiting
- Hospital Universitario Marqués de Valdecilla (Adults and Pediatrics)Recruiting
- Hospital Universitari Vall d'Hebrón - Institut de Recerca (Adults and Pediatrics)Recruiting
- Hospital General Universitario Gregorio Marañón (Adults and Pediatrics)Recruiting
- University Hospital Virgen del Rocio (Adults and Pediatrics)Recruiting
- Hospital Universitario La Fe (Adults and Pediatrics)Recruiting
- University Hospitals Birmingham NHS Foundation Trust (Adults only)Recruiting
- King's College Hospital NHS Foundation Trust (Adults only)Recruiting
- Imperial College Healthcare NHS Trust (Adults only)Recruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Experimental
Experimental
Experimental
SOT cohort -Subgroup A
SOT cohort -Subgroup B
HCT cohort
Participants who have failed rituximab will receive IV tabelecleucel.
Participants who have failed both rituximab and chemotherapy will receive IV tabelecleucel.
Participants who have failed rituximab will receive IV tabelecleucel.