Relapsed/Refractory Diffuse Large B cell Lymphoma (r/r DLBCL). MedDRA version: 21.0 Level: PT Classification code 10012822 Term: Diffuse large B-cell lymphoma refractory System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Sponsors
Kite Pharma, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 101. Histologically proven large B-cell lymphoma including the following types defined by WHO 2016 (Swerdlow et al, 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 o 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) ? Partial response (PR) as best response after at least 6 cycles, and biopsy-proven residual disease or disease progression = 12 months of therapy o Relapsed disease defined as complete remission to first-line therapy followed by biopsy-proven disease relapse = 12 months of first-line therapy 103. Subjects must have received adequate first-line therapy including at a minimum: o Anti-CD20 monoclonal antibody unless investigator determines that tumor is CD20 negative, and o An anthracycline containing chemotherapy regimen 104. Intent to proceed to HDT and ASCT if response to second-line therapy 105. Subjects must have radiographically documented disease 106. No known history or suspicion of central nervous system (CNS) involvement by lymphoma 107. At least 2 weeks or 5 half-lives, whichever is shorter, must have elapsed since any prior systemic cancer therapy at the time the subject provides consent 108. Age 18 years or older at the time of informed consent 109. ECOG performance status of 0 or 1 110. Adequate bone marrow, renal, hepatic, pulmonary and cardiac function defined as: o Absolute neutrophil count (ANC) =1000/µL o Platelet count = 75,000/µL o Absolute lymphocyte count = 100/µL o Creatinine clearance (as estimated by Cockcroft Gault) = 60 mL/min o Serum alanine aminotransferase/aspartate aminotransferase (ALT/AST) = 2.5 upper limit of normal (ULN) o Total bilirubin = 1.5 mg/dl, except in subjects with Gilbert’s syndrome o Cardiac ejection fraction = 50%, no evidence of pericardial effusion as determined by an echocardiogram (ECHO), and no clinically significant electrocardiogram (ECG) findings o No clinically significant pleural effusion o 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) Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 87 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 263
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 live, attenuated vaccine within 6 weeks prior to initiation of study treatment, or anticipation of need for such a vaccine d
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine if axicabtagene ciloleucel is superior to SOC as measured by event-free survival (EFS), as determined by blinded central review;Secondary Objective: - To evaluate the effect of axicabtagene ciloleucel compared to SOC on objective response rate (ORR), as determined by blinded central review - To evaluate the effect of axicabtagene ciloleucel compared to SOC on overall survival (OS) - To evaluate the effect of axicabtagene ciloleucel compared to SOC on progression-free survival (PFS) - To evaluate the effect of axicabtagene ciloleucel compared to SOC on duration of response (DOR) and duration of complete response among responding subjects as determined by blinded central review - To evaluate the safety of axicabtagene ciloleucel compared to SOC - To evaluate the effect of axicabtagene ciloleucel on patient reported outcomes (PROs) and quality of life (QoL) compared to SOC ;Primary end point(s): Event Free Survival (EFS): EFS is defined as the time from randomization to the earliest date of disease progression per the Lugano Classification, 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.;Timepoint(s) of evaluation of this end point: The primary analysis of EFS will be conducted when all subjects have had the opportunity to be followed to the Month 9 disease assessment, and approximately 250 EFS events have been observed. The acceptable lower limit for the observed total EFS events is 225, which is to maintain the power for the primary analysis of EFS to within 5% of the targeted 90%. If more than 250 EFS events are observed at the time of the data cutoff for the primary analysis, all observed events will be used in the | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 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 EORTC QLQ-C30 • Changes from screening to post baseline in the EQ-5D-5L index and VAS scores ;Timepoint(s) of evaluation of this end point: ORR is defined as the incidence of either a complete response or a partial response by the Lugano Classification as determined by blinded central review. Modified EFS is defined the same way as EFS, except that failure to attain CR or PR by Day 150 assessment is not considered as an event. OS is defined as the time from randomization to death from any cause. Subjects who have not died by the analysis data cutoff date will have survival time censored at their last date known to be alive. For subjects alive or dead after the data cutoff date, survival time will be censored at the data cutoff date. EFS, PFS, DOR timepoints of evaluation can be found in section 10.2.3. of the protocol. | — |
Countries
Australia, Austria, Belgium, Canada, France, Germany, Israel, Italy, Netherlands, Spain, Sweden, Switzerland, United Kingdom, United States
Contacts
Public ContactRegulatory Affairs
Kite Pharma, Inc.
Outcome results
None listed