large B cell lymphoma
Conditions
Interventions
Single arm:Axicabtagene Ciloleucel Injection
Sponsors
Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: (1) Histologically proven large B-cell lymphoma including the following types defined by World Health Organization 2016: Diffuse large B-cell lymphoma (DLBCL) not otherwise specified (including activated B-cell–like [ABC]/germinal center B-cell–like [GCB]); High grade B-cell lymphoma with or without MYC and B-cell lymphoma 2 (BCL2) and/or BCL6 rearrangement; DLBCL arising from follicular lymphoma; T-cell/histiocyte-rich large B-cell lymphoma; DLBCL associated with chronic inflammation; Primary cutaneous DLBCL, leg type; Epstein-Barr virus + DLBCL. (2) Relapsed or refractory disease after first-line chemoimmunotherapy a) Refractory disease defined as no complete remission to first-line therapy; patients who were intolerant to first-line therapy were excluded ? Progressive disease (PD) as best response to first-line therapy ? Stable disease (SD) as best response after at least four cycles of first-line therapy (e.g., 4 cycles of rituximab-cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, and prednisone) ? Partial response (PR) as best response after at least six cycles and biopsy-proven residual disease or disease progression =12 months of therapy b) Relapsed disease defined as complete remission to first-line therapy followed by biopsy-proven disease relapse =12 months of first-line therapy (3) Patients must have received adequate first-line therapy including at a minimum: a) Anti-CD20 monoclonal antibody unless investigator determines that tumor is CD20 negative, and b) An anthracycline containing chemotherapy regimen (4) Patients must have had radiographically documented disease (5) No known history or suspicion of central nervous system (CNS) involvement by lymphoma (6) At least two weeks or five half-lives, whichever is shorter, must have had elapsed since any prior systemic cancer therapy at the time the patient provides consent (7) The toxic reaction caused by previous anti-lymphoma treatment must be stable and restored to grade 1 or lower (except for the toxicity without clinical significance, such as alopecia). (8) Age 18 years or older at the time of informed consent (9) Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 (10) Adequate bone marrow, renal, hepatic, pulmonary, and cardiac function (11) 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 were not considered to be of childbearing potential). Male and female subjects with fertility agreed to take highly effective contraceptive methods during the entire study period and within 6 months after infusion.
Exclusion criteria
Exclusion criteria: (1)History of malignancy other than nonmelanoma skin cancer or carcinoma in situ (e.g., cervix, bladder, breast) unless disease free for at least 3 years (2)History of Richter’s transformation of chronic lymphocytic leukemia or primary mediastinal large B-cell lymphoma (3)History of autologous or allogeneic stem cell transplant (4)Received more than one line of therapy for DLBCL (5)Prior CD19 targeted therapy (6)Treatment with systemic immunostimulatory agents (including, but not limited to, interferon and interleukin-2) within six weeks or five half-lives (whichever shorter)of the drug prior to the first dose of Axicabtagene Ciloleucel (7)Prior chimeric antigen receptor (CAR) therapy or other genetically modified T-cell therapy (8)History of severe, immediate hypersensitivity reaction attributed to aminoglycosides, tocilizumab, and any drug that needs to be used in this study. (9)Presence of fungal, bacterial, viral, or other infection that is uncontrolled or requiring intravenous (IV) antimicrobials for management. Simple urinary tract infection and uncomplicated bacterial pharyngitis are permitted if responding to active treatment (10)Known history of infection with human immunodeficiency virus (HIV) or anti-Treponema pallidum antibody (TP-Ab positive) 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 (11)Active tuberculosis (12)Presence of any indwelling line or drain (e.g., 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 (13)Patients with detectable cerebrospinal fluid malignant cells or known brain metastases or with a history of cerebrospinal fluid malignant cells or brain metastases (14)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 (15)Patients with cardiac atrial or cardiac ventricular lymphoma involvement (16)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 (17)Requirement for urgent therapy due to tumor mass effects within 6 weeks, such as bowel obstruction or blood vessel or airway compression (18)History of autoimmune disease requiring systemic immunosuppression and/or systemic disease modifying agents within the last 2 years (19)History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, idiopathic pneumonitis, or evidence of activepneumonitis per chest computed tomography (CT) scan at screening. History of radiation pneumonitis in the radiation field (fibrosis) is allowed (20)History of symptomatic deep vein thrombosis or pulmonary embolism within 6 months of enrollment (21)Any medical condition likely to interfere with assessment of safety or efficacy of study treatment (22) Treatment with a live, attenuated vaccine within 6 weeks prior to initiation of study treatment or anticipation
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Best objective response rate; | — |
Secondary
| Measure | Time frame |
|---|---|
| Complete response rate;Partial response rate;Duration of remission;Progression-free survival;Event-free survival;Overall survival ;Incidence of adverse events (AE) ;Incidence of Serious adverse events (SAE) ;abnormal laboratory test values; | — |
Countries
China
Contacts
Public ContactYu Hu
Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
Outcome results
None listed