A Study of WZTL-002 CAR T-cells for Adults With Relapsed Large B-cell Lymphoma

NCT06486051 | Recruiting Phase 2 DMC

• 2 other identifiers: WZTL002-2U1111-1305-7917
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 3

Brief 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

Conditions

Large B-cell Lymphoma; Diffuse Large B-Cell Lymphoma, Not Otherwise Specified; Primary Mediastinal Large B-cell Lymphoma (PMBCL); Transformed Non-Hodgkin Lymphoma

Keywords

Chimeric Antigen Receptor Therapy; CD19 Antigen; Toll-Like Receptor 2; CD28 Antigen; Relapsed non-Hodgkin Lymphoma; Refractory non-Hodgkin Lymphoma; Adoptive Cellular Immunotherapy

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (8)

• Complete response (CR) rate per central assessment

  3 months after WZTL-002 administration

• Objective response rate (ORR) per investigator and per central assessment

  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)

  At Months 3, 6, 9, 12, 18, and 24 after WZTL-002 administration

• Cytokine release syndrome (CRS) rate and grade

  3 months after WZTL-002 administration

• Number and severity of adverse effects

  From screening until 24 months after WZTL-002 administration

Study Arms (1)

WZTL002 CAR T-cells

EXPERIMENTAL

Administered at a dose of 0.5 to 1.0x10\^6 CAR+ cells per kg of body weight, capped at 0.5 to 1x10\^8 cells for subjects weighing 100kg or more."

Drug: Fludarabine; Drug: Cyclophosphamide; Biological: WZTL-002 CAR T-cells

Interventions

Fludarabine DRUG

30 mg/m\^2/day IV for three consecutive days

WZTL002 CAR T-cells

Cyclophosphamide DRUG

500 mg/m\^2/day IV for three consecutive days

WZTL002 CAR T-cells

WZTL-002 CAR T-cells BIOLOGICAL

WZTL-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.

Also known as: 1928T2z CAR T-cells

WZTL002 CAR T-cells

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• Large B-cell lymphomas of the following histological subtypes:
• Diffuse LBCL, not otherwise specified
• Diffuse large B-cell lymphoma/high grade B-cell lymphoma with MYC and BCL2 rearrangements
• Large B-cell lymphoma with IRF4 rearrangement
• High grade B-cell lymphoma with 11q aberrations
• High grade B-cell lymphoma, not otherwise specified
• Primary mediastinal large B-cell lymphoma
• Follicular large B-cell lymphoma
• EBV-positive diffuse large B-cell lymphoma, not otherwise specified
• Diffuse large B-cell lymphoma associated with chronic inflammation
• Primary cutaneous DLBCL, leg type
• Large B-cell lymphoma of one of the above subtypes that has transformed from follicular or marginal zone lymphoma

You may not qualify if:

• 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
• B-cell non-Hodgkin lymphoma of the following subtypes, as per the 2022 WHO classification of haematolymphoid tumours:
• Richter transformation of chronic lymphocytic leukaemia
• T-cell/histiocyte rich LBCL
• Primary LBCL of immune-privileged sites
• Fluid overload associated LBCL
• Fibrin-associated LBCL
• Plasmablastic lymphoma
• Mediastinal grey zone lymphoma
• Intravascular LBCL
• ALK-positive large B-cell lymphoma
• Lymphomatoid granulomatosis
• Burkitt lymphoma
• Primary effusion lymphoma

Sponsors & Collaborators

• Wellington Zhaotai Therapies Limited: collaborator
• Malaghan Institute of Medical Research: lead
• BioOra Limited: collaborator

Study Sites (3)

Christchurch Hospital

Christchurch, Christchurch Central, 8011, New Zealand

RECRUITING

Wellington Hospital

Newtown, Wellington Region, 6021, New Zealand

RECRUITING

Auckland City Hospital

Auckland, 1023, New Zealand

RECRUITING

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin

Interventions

fludarabine; Cyclophosphamide

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Study Officials

• Philip George, MBChB

  Te Whatu Ora Health New Zealand, Capital Coast & Hutt Valley

  PRINCIPAL INVESTIGATOR

• Robert Weinkove, PhD

  Malaghan Institute of Medical Research

  STUDY CHAIR

Central Study Contacts

Brittany Lavender

CONTACT

+64 4 499 6914; clinicaltrialmanagement@malaghan.org.nz

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 20, 2024
• First Posted: July 3, 2024
• Study Start: July 12, 2024
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): June 30, 2028
• Last Updated: March 3, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

NZ (3)