A Phase 1 interventional study of WZTL002-1 (1928T2z CAR-T cells) and Cyclophosphamide and Fludarabine lymphodepleting chemotherapy in Lymphomas Non-Hodgkin's B-Cell, Diffuse Large B-cell Lymphoma (DLBCL) and Primary Mediastinal B-cell Lymphoma (PMBCL), sponsored by Malaghan Institute of Medical Research. Active, not recruiting at 1 site in New Zealand. Open to participants aged 16 Years to 75 Years. Per ClinicalTrials.gov, last updated 2024-08-21.
Sponsored by Malaghan Institute of Medical Research · Phase 1, Interventional, and Treatment
This Phase 1, single centre, open label dose escalation study aims to identify a safe dose of third-generation anti-CD19 CAR T-cells (WZTL-002) in the treatment of patients with relapsed or refractory (r/r) B-cell Non Hodgkin Lymphoma, for use in further efficacy trials. An expansion cohort will assess automated closed-system manufacture of WZTL-002 and outpatient management of participants.
This is a Phase 1 study, designed to evaluate the safety, feasibility, efficacy and kinetics of third-generation autologous anti-CD19 CAR T-cells, WZTL-002, in patients with relapsed or refractory B-cell Non-Hodgkin Lymphoma without other curative options. The initial dose escalation cohort will use a 3+3 dose escalation design to identify a Maximum Tolerated Dose (MTD) of WZTL-002 using pre-defined Dose Limiting Toxicity (DLT) criteria. Within a subsequent dose expansion cohort at the recommended phase 2 dose, an automated closed-system manufacturing process for WZTL-002 and outpatient clinical management will be implemented.
Eligible participants will undergo leukapheresis to harvest peripheral blood mononuclear cells, the starting material for the manufacture of the autologous third generation anti-CD19 CAR T-cell product, WZTL-002. After WZTL-002 manufacture and confirmation that product release criteria are met, participants will receive lymphodepleting chemotherapy comprising fludarabine and cyclophosphamide on days -5 to day -3, inclusive. WZTL-002 will be administered intravenously on day 0 as a single dose.
Following WZTL-002 administration, participants will be monitored closely for 14 days, including targeted assessments for the specific CAR T-cell related toxicities of Cytokine Release Syndrome (CRS) and Immune Effector Cell Neurotoxicity Syndrome (ICANS). Initial DLT assessment will occur at day 21 after WZTL-002 infusion. A PET/CT Scan to assess treatment response will take place 3 months after WZTL-002 infusion, marking the end of the primary follow up period. The secondary follow up period will occur between 3 months up until 2 years after WZTL-002 treatment. Long term follow up within the trial will occur annually from 2 to 5 years after WZTL-002 treatment, with further follow-up within the Center for International Blood and Marrow Transplant Research (CIBMT) Cellular Therapies Registry and the Australasian Bone Marrow Transplant Recipient Registry (ABMTRR). In addition to clinical data, this study incorporates sample collection for exploratory endpoints including serum cytokine profile following WZTL-002 infusion, and WZTL-002 expansion, persistence and phenotype.
5,579 studies on the registry are indexed under Lymphoma; 825 are open to participants now.
This study's enrollment of 30 is below the median of 40 across 4,509 interventional studies indexed under Lymphoma.
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No serious cardiac, pulmonary, hepatic or renal disease.
Exclusion Criteria:
Serologic status reflecting active viral hepatitis B or any history of hepatitis C infection as follows:
A starting WZTL-002 dose of 5 × 10\^4 CAR T-cells/kg has been selected with four possible dose level cohorts proposed. Escalation to a higher dose cohort will be based on assessment of dose limiting toxicities to determine safety at a given dose level.
Biological: WZTL002-1 (1928T2z CAR-T cells) · Drug: Cyclophosphamide and Fludarabine lymphodepleting chemotherapy
WZTL-002 comprises autologous third-generation anti-CD19 chimeric antigen receptor T-cells (termed 1928T2z). The chimeric antigen receptor in WZTL-002 incorporates the FMC63 anti-CD19 soluble chain variable fragment extracellularly, and portions of both CD28 and the Toll/interleukin-1 receptor (TIR) domain of Toll Like Receptor 2 (TLR2) as intracellular co-stimulatory domains, alongside CD3ζ. WZTL-002 (autologous 1928T2z CAR T-cells) will be administered on D0 as a single IV infusion, following lymphodepleting chemotherapy.
Cyclophosphamide 500 mg/m\^2 IV on days -5 to -3, inclusive. Fludarabine 30 mg/m\^2 IV on days -5 to -3, inclusive
Number and severity of adverse events assessed by CTCAE v5.0, except for Cytokine Release Syndrome and Immune Effector Cell-Associated Neurotoxicity Syndrome, which will be assessed by ASTCT consensus grading criteria
Determine the safety profile of WZTL-002, anti-CD19 CAR T-cells by measuring frequency and severity of adverse events
Time frame: 3 months after administration
Feasibility of Manufacture
To investigate the feasibility of manufacture and treatment with WZTL-002, as determined by the proportion of enrolled participants undergoing at least one study leukapheresis procedure that receive WZTL-002
Time frame: 3 months after administration
Overall Response Rate
To estimate the overall response rate (ORR) as determined by complete response (CR) plus partial response (PR) 3 months after WZTL-002 administration
Time frame: 3 months after administration
Cumulative CR rate
To determine the cumulative CR rate 6 months after WZTL-002 administration
Time frame: 6 months after administration
Relapse-free survival
To estimate the relapse-free survival (RFS) for subjects treated with WZTL-002 over a period of 24 months after WZTL-002 administration
Time frame: 24 months after administration
Overall survival
To estimate the overall survival (OS) distribution for subjects treated with WZTL-002 over a period of 24 months after WZTL-002 administration
Time frame: 24 months after administration
Recommended dose
To determine the recommended phase 2 dose of WZTL-002 for treatment of R/R B-NHL
Time frame: 3 months after administration
Plan to share: Yes — All IPD that underlie results in a publication
This study is active, not recruiting, as verified in Aug 2024. You cannot join it, but the record below documents what was studied.
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Malaghan Institute of Medical Research