Ignite Creation Date:
2025-12-24 @ 11:40 PM
Ignite Modification Date:
2026-01-03 @ 5:06 PM
Study NCT ID:
NCT06486051
Status:
RECRUITING
Last Update Posted:
2025-02-14
First Post:
2024-06-20
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
A Study of WZTL-002 CAR T-cells for Adults With Relapsed Large B-cell Lymphoma
Sponsor:
Malaghan Institute of Medical Research
Organization:
Study Overview
Official Title:
A Phase 2 Trial to Evaluate the Efficacy and Safety of WZTL-002 in Patients With Relapsed or Refractory Large B-cell Lymphoma (ENABLE-2)
Status:
RECRUITING
Status Verified Date:
2025-02
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
ENABLE-2
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
* 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
Detailed Description:
WZTL-002 is a third-generation CAR T-cell product comprising autologous T-cells transduced to express a CAR directed against CD19 and incorporating a Toll-like receptor 2 (TLR2) co-stimulatory domain interposed between CD28 and CD3ΞΆ signalling domains. The trial will screen up to 80 patients in order to enrol and treat approximately 60 participants with WZTL-002. This is a single arm open-label phase 2 trial designed to evaluate the efficacy, safety, cellular kinetics and pharmacodynamic properties of WZTL-002 for the second- or third-line treatment of r/r LBCL.
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.
After WZTL-002 administration, participants will be monitored closely for 14 days including targeted assessments for the specific CAR T-cell related toxicities Cytokine Release Syndrome (CRS) and Immune Effector Cell Neurotoxicity Syndrome (ICANS). CRS, ICANS and grade 3 or higher neutropenia, thrombocytopenia or anemia persisting beyond day 30 will be recorded as adverse events of special interest. PET/CT scans to assess treatment response will take place at screening, pre-lymphodepletion and at 28 days, 3 months and 6 months after WZTL-002 infusion, and CT scans to assess duration of response at 12 and 24 months after WZTL-002 infusion. Samples will be taken to determine WZTL-002 cellular kinetics and the depth and duration of B-cell aplasia (pharmacodynamic analysis).
Follow-up beyond month 24 will take place within the Center for International Blood and Marrow Transplant Research (CIBMT) Cellular Therapies Registry or the Australasian Bone Marrow Transplant Recipient Registry (ABMTRR), and in a subsequent long-term follow-up study.
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.
After WZTL-002 administration, participants will be monitored closely for 14 days including targeted assessments for the specific CAR T-cell related toxicities Cytokine Release Syndrome (CRS) and Immune Effector Cell Neurotoxicity Syndrome (ICANS). CRS, ICANS and grade 3 or higher neutropenia, thrombocytopenia or anemia persisting beyond day 30 will be recorded as adverse events of special interest. PET/CT scans to assess treatment response will take place at screening, pre-lymphodepletion and at 28 days, 3 months and 6 months after WZTL-002 infusion, and CT scans to assess duration of response at 12 and 24 months after WZTL-002 infusion. Samples will be taken to determine WZTL-002 cellular kinetics and the depth and duration of B-cell aplasia (pharmacodynamic analysis).
Follow-up beyond month 24 will take place within the Center for International Blood and Marrow Transplant Research (CIBMT) Cellular Therapies Registry or the Australasian Bone Marrow Transplant Recipient Registry (ABMTRR), and in a subsequent long-term follow-up study.
Study Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
Secondary ID Infos
| Secondary ID | Type | Domain | Link | View |
|---|---|---|---|---|
| U1111-1305-7917 | OTHER | World Health Organization | View |