The goal of this clinical trial is to learn if a new type of chimeric antigen receptor (CAR) T-cell therapy called atlacabtagene autoleucel is effective and safe for the treatment large B-cell lymphomas (LBCL) that have not responded to or have come back after standard chemotherapy. The main questions this trial aims to answer are:
* What is the likelihood of complete response of the lymphoma after atlacabtagene autoleucel treatment? * What is the risk of altered brain function (neurotoxicity) after atlacabtagene autoleucel?
All eligible participants will receive atlacabtagene autoleucel; the researchers will compare the complete response rate and neurotoxicity rate with historical groups of patients who were treated with similar therapies.
Participants will:
* Have a procedure to gather white blood cells * Receive chemotherapy to prepare for the CAR T-cells * Receive atlacabtagene autoleucel CAR T-cells through a vein * Be monitored closely for the first 14 days for certain side effects * Have scans 28 days and 3, 6, 12 and 24 months after atlacabtagene autoleucel CAR T-cells to check if the treatment has worked
Age 18 to 75 years (inclusive) at the time of informed consent
Signed written informed consent for this trial
Biopsy-proven relapsed or treatment-refractory B-cell non-Hodgkin lymphoma of the following subtypes, as per the 2022 WHO classification of haematolymphoid tumours
Diffuse LBCL, not otherwise specified
Active central nervous system (CNS) involvement by lymphoma. In patients with a history of CNS disease or a clinical suspicion of current CNS disease, lumbar puncture and MRI brain must be performed within 30 days of enrolment to exclude current CNS involvement.
Active CNS pathology including: epilepsy, seizure within the preceding year, aphasia, paresis, stroke, dementia, psychosis within the preceding year, severe brain injury, Parkinson disease, or cerebellar disease
Richter transformation of chronic lymphocytic leukaemia
T-cell/histiocyte rich LBCL
Single group
Fludarabine
Drug30 mg/m\^2/day IV for three consecutive days
Cyclophosphamide
Drug500 mg/m\^2/day IV for three consecutive days
WZTL-002 CAR T-cells
Biological/VaccineWZTL-002 comprises autologous T-cells transduced to express the third-generation 1928T2z chimeric antigen receptor, which recognises the CD19 antigen present on malignant and normal B-cells. The chimeric antigen receptor (CAR) incorporates an extracellular scFv specific for CD19, the intracellular signalling domains of CD28 and CD3ζ, and an intracellular co-stimulatory domain derived from TLR2 interposed between CD28 and CD3ζ. On Day 0, the WZTL-002 CAR T-cell product is administered intravenously two days after completing lymphodepleting chemotherapy.
Complete response (CR) rate per Investigator assessment
Investigator-assessed CR rate according to Lugano Response Criteria
Immune effector cell-associated neurotoxicity syndrome (ICANS) rate
Proportion of participants with ICANS (any grade) as assessed by American Society for Transplantation and Cellular Therapy (ASTCT) criteria
Complete response (CR) rate per central assessment
Complete response (CR) rate per central assessment according to Lugano Response criteria
Objective response rate (ORR) per investigator and per central assessment
Objective response rate comprising CR rate plus partial response (PR) rate, according to Lugano Response Criteria
Progression free survival (PFS), Event-free survival (EFS), Overall survival (OS) and Duration of Response (DOR)
To estimate the progression-free, event-free, overall survival and duration of response after treatment with atlacabtagene autoleucel
Cytokine release syndrome (CRS) rate and grade
CRS rate and grade, as assessed by ASTCT consensus criteria
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Malaghan Institute of Medical Research
Lead sponsor
BioOra Limited
Collaborator
Wellington Zhaotai Therapies Limited
Collaborator
