A Study of WZTL-002 CAR T-cells for Adults With Relapsed Large B-cell Lymphoma
NCT Number: NCT06486051
Acronym: ENABLE-2
Status: RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE2
Conditions: Large B-cell Lymphoma|Diffuse Large B-Cell Lymphoma, Not Otherwise Specified|Primary Mediastinal Large B-cell Lymphoma (PMBCL)|Transformed Non-Hodgkin Lymphoma
Interventions: DRUG: Fludarabine|DRUG: Cyclophosphamide|BIOLOGICAL: WZTL-002 CAR T-cells
Sponsor: Malaghan Institute of Medical Research
Collaborators: BioOra Limited|Wellington Zhaotai Therapies Limited
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 60
Study Design: Allocation: NA|Intervention Model: SINGLE_GROUP|Masking: NONE|Primary Purpose: TREATMENT
Start Date: 2024-07-12
Completion Date: 2028-06-30
Locations: Wellington Hospital, Newtown, Wellington, 6021, New Zealand

Summary:
The goal of this clinical trial is to learn if a new type of chimeric antigen receptor (CAR) T-cell therapy called WZTL-002 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 WZTL-002 treatment?
* What is the risk of altered brain function (neurotoxicity) after WZTL-002?

All eligible participants will receive WZTL-002; 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 WZTL-002 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 WZTL-002 CAR T-cells to check if the treatment has worked

Primary Outcome Measures: Complete response (CR) rate per Investigator assessment, Investigator-assessed CR rate according to Lugano Response Criteria, 3 months after WZTL-002 administration|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, 3 months after WZTL-002 administration
Secondary Outcome Measures: Complete response (CR) rate per central assessment, Complete response (CR) rate per central assessment according to Lugano Response criteria, 3 months after WZTL-002 administration|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, At 3 and at 6 months after WZTL-002 administration|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 WZTL-002, At Months 3, 6, 9, 12, 18, and 24 after WZTL-002 administration|Cytokine release syndrome (CRS) rate and grade, CRS rate and grade, as assessed by ASTCT consensus criteria, 3 months after WZTL-002 administration|Number and severity of adverse effects, Adverse events will be graded by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v5.0 criteria (except for CRS and ICANS; see separate endpoints), From screening until 24 months after WZTL-002 administration|Hospitalisation (inpatient) days, Number of intensive care unit (ICU) inpatient days and non-ICU inpatient days and reason for hospitalisation, 3 months after WZTL-002 administration|Health-related quality of life (HRQoL) as Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30), EORTC QLQ-C30 is a 30-item participant self-reported questionnaire composed of multi-item and single scales. Participants rate items and a score from 0 to 100 for the global health status scale and for each functional scale is calculated. A higher score indicates a better level of quality of life or function, and positive changes from baseline indicate improvement, Upto 24 months after WZTL-002 administration|European Quality of Life 5-Dimensions 5-Levels Health Questionnaire (EQ-5D-5L), The EQ-5D-5L measures health outcomes using a visual analogue score (VAS) to record a participant's self-rated health on a scale from 0 to 100, where 100 is 'the best health you can imagine' and 0 is 'the worst health you can imagine.' A higher score indicates a better health outcome., Upto 24 months after WZTL-002 administration