Diffuse Large B Cell Lymphoma (DLBCL) lymphatic cancer
Conditions
Interventions
- Axicabtagene ciloleucel arm
Subjects randomized to the axicabtagene ciloleucel arm of the study will
receive a 3 day conditioning chemotherapy regimen consisting of fludarabine 30
mg/m2/day and cy
Sponsors
Kite Pharma Inc
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 101. Histologically proven large B-cell lymphoma including the following types defined by WHO 2016 o DLBCL not otherwise specified (including ABC/GCB) o HGBL with or without MYC and BCL2 and/or BCL6 rearrangement o DLBCL arising from FL o T-cell/histiocyte rich large B-cell lymphoma o DLBCL associated with chronic inflammation o Primary cutaneous DLBCL, leg type o Epstein-Barr virus (EBV) + DLBCL 102. Relapsed or refractory disease after first-line chemoimmunotherapy - Refractory disease defined as no complete remission to first-line therapy; subjects who are intolerant to first-line therapy are excluded Progressive disease (PD) as best response to first-line therapy Stable disease (SD) as best response after at least 4 cycles of first-line therapy (eg, 4 cycles of R-CHOP) PR as best response after at least 6 cycles, and biopsy-proven residual disease or disease progression =1000/µL - Platelet count >= 75,000/µL - Absolute lymphocyte count >= 100/µL - Creatinine clearance (as estimated by Cockcroft Gault) >= 60 mL/min - Serum alanine aminotransferase/aspartate aminotransferase (ALT/AST) = 50%, no evidence of pericardial effusion as determined by an echocardiogram (ECHO), and no clinically significant electrocardiogram (ECG) findings - No clinically significant pleural effusion - Baseline oxygen saturation > 92% on room air 111. Females of childbearing potential must have a negative serum or urine pregnancy test (females who have undergone surgical sterilization or who have been postmenopausal for at least 2 years are not considered to be of childbearing potential)
Exclusion criteria
Exclusion criteria: 201. History of malignancy other than nonmelanoma skin cancer or carcinoma in situ (eg cervix, bladder, breast) unless disease free for at least 3 years 202. History of Richter*s transformation of CLL or PMBCL 203. History of autologous or allogeneic stem cell transplant 204. Received more than one line of therapy for DLBCL 205. Prior CD19 targeted therapy 206. Treatment with systemic immunostimulatory agents (including but not limited to interferon and IL-2) within 6 weeks or 5 half-lives of the drug, whichever is shorter, prior to the first dose of axicabtagene ciloleucel or SOC 207. Prior chimeric antigen receptor therapy or other genetically modified T-cell therapy, or prior randomization into ZUMA-7 208. History of severe, immediate hypersensitivity reaction attributed to aminoglycosides 209. Presence of fungal, bacterial, viral, or other infection that is uncontrolled or requiring intravenous (IV) antimicrobials for management. Simple urinary tract infection (UTI) and uncomplicated bacterial pharyngitis are permitted if responding to active treatment. 210. Known history of infection with human immunodeficiency virus (HIV) or hepatitis B (HBsAg positive) or hepatitis C virus (anti-HCV positive). If there is a positive history of treated hepatitis B or hepatitis C, the viral load must be undetectable per quantitative polymerase chain reaction (PCR) and/or nucleic acid testing. 211. Active tuberculosis 212. Presence of any indwelling line or drain (eg, percutaneous nephrostomy tube, indwelling Foley catheter, biliary drain, or pleural/peritoneal/pericardial catheter). Dedicated central venous access catheters such as a Port-a-Cath or Hickman catheter are permitted. 213. Subjects with detectable cerebrospinal fluid malignant cells or known brain metastases, or with a history of cerebrospinal fluid malignant cells or brain metastases. 214. History or presence of non-malignant CNS disorder such as seizure disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease with CNS involvement 215. Subjects with cardiac atrial or cardiac ventricular lymphoma involvement 216. History of myocardial infarction, cardiac angioplasty or stenting, unstable angina, New York Heart Association Class II or greater congestive heart failure, or other clinically significant cardiac disease within 12 months of enrollment 217. Requirement for urgent therapy due to tumor mass effects such as bowel obstruction or blood vessel compression 218. History of autoimmune disease, requiring systemic immunosuppression and/or systemic disease modifying agents within the last 2 years. 219. History of idiopathic pulmonary fibrosis, organizing pneumonia (eg, bronchiolitis obliterans), drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis per chest computed tomography (CT) scan at screening. History of radiation pneumonitis in the radiation field (fibrosis) is allowed. 220. History of symptomatic deep vein thrombosis or pulmonary embolism within 6 months of enrollment 221. Any medical condition likely to interfere with assessment of safety or efficacy of study treatment 222. History of severe immediate hypersensitivity reaction to tocilizumab or any of the agents used in this study 223. Treatment with a l
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary endpoint: Event Free Survival (EFS): EFS is defined as the time from randomization to the earliest date of disease progression per the Lugano Classification (Cheson et al, 2014), commencement of new lymphoma therapy, or death from any cause. Subjects not meeting the criteria for these events by the analysis data cutoff date will be censored. For the primary analysis of EFS, disease progression events and censoring times will be determined by blinded central review. Events of new therapy and death will be based on the clinical trial database. | — |
Secondary
| Measure | Time frame |
|---|---|
| Key secondary endpoints (in order of hierarchical testing): - Objective response rate - Overall survival Secondary endpoints: - EFS based on investigator disease assessments - Modified EFS based on blinded central review and on investigator disease assessments - Progression-free survival - Duration of response and complete response - Incidence of adverse events and clinically significant changes in safety lab values including antibodies to axicabtagene ciloleucel - Changes from screening to post baseline in the global health status QoL scale and the physical functioning domain of the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Cancer-30 (EORTC QLQ-C30) - Changes from screening to post baseline in the Euro-QOL, Five Dimensions, Five Levels (EQ-5D-5L) index and visual analog scale (VAS) scores Exploratory endpoints: For axicabtagene ciloleucel treatment arm only: • Levels of anti CD19 chimeric antigen receptor (CAR) T cells in blood • Levels of cytokines in serum For both treatment arms: • Tumor molecular and histological characteristics by levels of PD-L1 and molecular and cytogenetic subclassifications • Changes in the work productivity and activity impairment (WPAI) from screening to post baseline • Time to next therapy | — |
Countries
Netherlands
Outcome results
None listed