Large B-cell LymphomaPhase 2ENABLE-2NCT06486051
A Study of Atlacabtagene Autoleucel CAR T-cells for Adults With Relapsed Large B-cell Lymphoma
A Phase 2 study testing Fludarabine, Cyclophosphamide and WZTL-002 CAR T-cells in people with Large B-cell Lymphoma and Diffuse Large B-Cell Lymphoma, Not Otherwise Specified, run by Malaghan Institute of Medical Research at 3 sites in New Zealand.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Large B-cell Lymphoma, Diffuse Large B-Cell Lymphoma, Not Otherwise Specified, Primary Mediastinal Large B-cell Lymphoma (PMBCL)
- What is being tested?
- Fludarabine, Cyclophosphamide and WZTL-002 CAR T-cells
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 3 sitesNew Zealand
- Study dates
- 12 Jul 2024to 30 Jun 2029
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 47Show fewer
- 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
- Received adequate first-line lymphoma therapy for the qualifying histology (as defined in inclusion criterion 3 above), comprising at least 2 cycles of a standard combination regimen incorporating an anthracycline and an anti-CD20 monoclonal antibody
- Relapsed or refractory disease meeting one of the following criteria:
- Relapsed or refractory within 12 months of first-line chemoimmunotherapy, defined as:
- Progressive disease following ≥ 2 cycles of chemoimmunotherapy, or
- Stable disease following ≥ 4 cycles of chemoimmunotherapy, or
- Partial response following ≥ 6 cycles of chemoimmunotherapy, or
- Complete response followed by biopsy-proven relapse within 12 months of completing first-line chemoimmunotherapy.
- Relapsed or refractory following second-line chemoimmunotherapy, defined as:
- Lack of complete response to, or relapse following, autologous stem cell transplantation as part of second-line therapy for the qualifying histology, or
- Inability to proceed to autologous stem cell transplantation due to lack of response to 2 cycles of second-line chemoimmunotherapy incorporating both a platinum agent and an anti-CD20 monoclonal antibody
- Positron emission tomography (PET) positive disease according to the Lugano 2014 criteria
- Available tumour tissue (comprising a tissue block or at least 6 unstained slides) for central histological review
- Lymphoma-related life expectancy at least 12 weeks, and life expectancy related to conditions other than lymphoma at least 12 months
- ECOG performance status of 0 or 1
- Adequate haematologic function, defined by:
- Neutrophils ≥ 1.0 × 10^9/L, and Platelets ≥ 75 × 10^9/L, and
- Lymphocytes ≥ 0.3 × 10^9/L
- Adequate renal function, defined by estimated creatinine clearance (eCrCl) or glomerular filtration rate (eGFR) >/= 45mL/min using the Cockroft Gault estimation, CKD-EPI equation or as assessed by direct measurement.
- Adequate hepatic function, defined by serum bilirubin < 2.5 × upper limit of normal (ULN) (unless attributable to Gilbert's syndrome) and alanine transaminase and aspartate aminotransferase < 3 × ULN.
- Adequate lung function, defined as ≤ Grade 1 dyspnoea according to NCI CTCAE v5.0, and oxygen saturation (sO2) ≥ 92% on room air.
- Adequate cardiac function, defined as left ventricular ejection fraction (LVEF) ≥ 40% as assessed by echocardiogram or multigated acquisition (MUGA), performed within 28 days of commencing screening.
- For female participants:
- Agree to use a condom if undertaking sexual activity with any partner during lymphodepleting chemotherapy, and
- If of reproductive potential agree to use a highly effective method of contraception from the time of enrolment until at least 12 months after administration of atlacabtagene autoleucel, or
- Are not of reproductive potential defined as either,
- being amenorrhoeic for at least 12 consecutive months with FSH 30 ≥ IU/L, or
- previously undergone a sterilisation procedure
- For male participants:
- Agree to use a condom if undertaking sexual activity with any partner during lymphodepleting chemotherapy, and
- If undertaking sexual activity with a female partner of reproductive potential agree to use a highly effective method of contraception from the time of enrolment until at least 12 months after administration of atlacabtagene autoleucel, and
- Agree not to donate sperm for conception, or to provide gametes for in vitro fertilisation for at least 12 months after administration of atlacabtagene autoleucel
- Participant agrees not to donate blood components at any time after receiving WZTL-002
Who cannot join
- 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
Show all 40Show fewer
- 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
- KSHV/HHV8-positive diffuse large B-cell lymphoma
- Patient has received 3 or more prior lines of therapy for LBCL, where 1 line of therapy is defined as 1 or more cycles of a combination chemoimmunotherapy with or without pre-planned consolidation therapy (radiotherapy, autologous stem cell transplant or immunotherapy)
- Requirement for urgent lymphoma therapy due to tumour-related symptoms, or due to imminent risk of blood vessel, airway, urinary tract, gastrointestinal tract, nerve or spinal cord compression
- Active autoimmune disease requiring current systemic immunosuppression
- Active sarcoidosis
- Prior solid organ transplantation or prior allogeneic stem cell transplantation (allo-SCT)
- Peripheral blood CD3+ T cells < 150/μL (0.15 x10^9/L) as assessed by lymphocyte subset analysis
- History of active malignancy other than B-cell malignancy within 2 years prior to enrolment, with the exception of: adequately treated in situ carcinoma of the cervix; adequately treated basal cell carcinoma (BCC) or squamous cell carcinoma (SCC) of the skin; other localised malignancy surgically resected (or radically treated with another treatment modality) with curative intent
- Prior treatment with:
- gene therapy (including CAR T-cell therapy) or CD19-targeted immunotherapy, or
- purine analogue (including bendamustine) or alemtuzumab within 6 months of enrolment, or
- bispecific T-cell engager, radiotherapy or an investigational medicine within 4 weeks of enrolment, or
- cytotoxic chemotherapy, systemic corticosteroids (at doses of ≥ 10 mg prednisone daily or equivalent), monoclonal antibody or antibody-drug conjugate (other than alemtuzumab) within 2 weeks of enrolment.
- Pregnant or lactating female
- Known sensitivity to immunoglobulin or to components of the IP
- Current or prior HIV infection
- Vaccination with a live virus within the 4 weeks of enrolment
- Inadequately-controlled systemic infection
- Serologic status reflecting active viral hepatitis B or active hepatitis C infection as follows:
- Presence of hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) with hepatitis B virus (HBV) DNA > 20 IU/mL. Patients with presence of HBcAb and/or HBsAg remain eligible if HBV DNA is undetectable (or is < 20 IU/mL), and provided they are receiving appropriate antiviral prophylaxis.
- Presence of active Hepatitis C infection as determined by Hepatitis C virus (HCV) RNA detected by PCR or nucleic acid testing (NAT). Patients with presence of HCV antibody, are eligible if HCV RNA is undetectable.
- Current New York Heart Association (NYHA) class 2 or higher cardiac symptoms, or myocardial infarction, unstable angina or other clinically significant cardiac disease within the past 6 months
- Significant concomitant illnesses which would in the Investigators opinion make the patient an unsuitable candidate for the trial
- Patients who have diminished capacity or any circumstance that would prohibit them from understanding and providing informed consent in accordance with ICH-GCP
- Patient does not provide consent to enrol to an International Cellular Therapy Registry
Trial locations and contacts
3 sites in 1 country. Contact the study team or a site near you to ask about taking part.
New Zealand3 sites, 3 recruiting
- Recruiting
Auckland City Hospital
Auckland, Auckland, 1023
Shailesh Patel, +6493074949 Ext 23921, Haemtrials@adhb.govt.nz
- Recruiting
Christchurch Hospital
Christchurch, Christchurch Central, 8011
Haematology Research Team, +64 3 03 364 0377, HaemClinTrials@cdhb.health.nz
- Recruiting
Wellington Hospital
Newtown, Wellington Region, 6021
Clinical Trial Unit, +64 4 918 5117, res-research@ccdhb.org.nz
About this study
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)
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?
Read more
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
Read the 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 CD3ζ 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.
- Conditions
- Large B-cell Lymphoma, Diffuse Large B-Cell Lymphoma, Not Otherwise Specified, Primary Mediastinal Large B-cell Lymphoma (PMBCL), Transformed Non-Hodgkin Lymphoma
- Being tested
- Fludarabine, Cyclophosphamide, WZTL-002 CAR T-cells
- Keywords
- Chimeric Antigen Receptor Therapy, CD19 Antigen, Toll-Like Receptor 2, CD28 Antigen, Relapsed non-Hodgkin Lymphoma, Refractory non-Hodgkin Lymphoma, Adoptive Cellular Immunotherapy
- Medical subject headings
- Lymphoma, Large B-Cell, Diffuse, Lymphoma, Non-Hodgkin
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FludarabineDrug
30 mg/m^2/day IV for three consecutive days
CyclophosphamideDrug
500 mg/m^2/day IV for three consecutive days
WZTL-002 CAR T-cellsBiological
Also called 1928T2z CAR T-cells
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.
| Study group | Role | What they receive |
|---|---|---|
| atlacabtagene autoleucel 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." Receives: Drug: Fludarabine; Drug: Cyclophosphamide; Biological: WZTL-002 CAR T-cells |
What is being measured
The primary outcome is the main question the study is designed to answer.
Complete response (CR) rate per Investigator assessment
Investigator-assessed CR rate according to Lugano Response Criteria
Measured: 3 months after atlacabtagene autoleucel 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
Measured: 3 months after atlacabtagene autoleucel administration
Secondary outcomes (8)
Complete response (CR) rate per central assessment
Complete response (CR) rate per central assessment according to Lugano Response criteria
Measured: 3 months after atlacabtagene autoleucel 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
Measured: At 3 and at 6 months after atlacabtagene autoleucel 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 atlacabtagene autoleucel
Measured: At Months 3, 6, 9, 12, 18, and 24 after atlacabtagene autoleucel administration
Cytokine release syndrome (CRS) rate and grade
CRS rate and grade, as assessed by ASTCT consensus criteria
Measured: 3 months after atlacabtagene autoleucel 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)
Measured: From screening until 24 months after atlacabtagene autoleucel administration
Hospitalisation (inpatient) days
Number of intensive care unit (ICU) inpatient days and non-ICU inpatient days and reason for hospitalisation
Measured: 3 months after atlacabtagene autoleucel 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
Measured: Upto 24 months after atlacabtagene autoleucel 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.
Measured: Upto 24 months after atlacabtagene autoleucel administration
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Jul 2024
- Study start12 Jul 2024
- Primary completion30 Jun 2027 (estimated)
- Study completion30 Jun 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Large B-cell LymphomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Malaghan Institute of Medical Research
- Sponsor type
- University, hospital or other
- Collaborators
- BioOra Limited, Wellington Zhaotai Therapies Limited
- Responsible party
- Sponsor
- Investigators
- Philip George, MBChB, Principal investigator, Te Whatu Ora Health New Zealand, Capital Coast & Hutt ValleyRobert Weinkove, PhD, Study chair, Malaghan Institute of Medical Research
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06486051
- Sponsor's protocol ID
- WZTL002-2
- Other IDs
- U1111-1305-7917
- Acronym
- ENABLE-2
- Status last verified
- Aug 2026
- First submitted
- 20 Jun 2024
- Last updated
- 7 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 7 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT06486051
- Acronym / sponsor ID
- ENABLE-2 / WZTL002-2
- 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
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- Malaghan Institute of Medical ResearchUniversity, hospital or other
- Collaborators
- BioOra Limited, Wellington Zhaotai Therapies Limited
- Study start
- 12 Jul 2024 (actual)
- Primary completion
- 30 Jun 2027 (estimated)
- Study completion
- 30 Jun 2029 (estimated)
- First posted
- 3 Jul 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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 CD3ζ 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| atlacabtagene autoleucel CAR T-cells | Experimental | Drug: Fludarabine, Drug: Cyclophosphamide, Biological: WZTL-002 CAR T-cellsAdministered 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." |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (47 listed)
- 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
- Received adequate first-line lymphoma therapy for the qualifying histology (as defined in inclusion criterion 3 above), comprising at least 2 cycles of a standard combination regimen incorporating an anthracycline and an anti-CD20 monoclonal antibody
- Relapsed or refractory disease meeting one of the following criteria:
Key exclusion criteria (40 listed)
- 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:
- Patient has received 3 or more prior lines of therapy for LBCL, where 1 line of therapy is defined as 1 or more cycles of a combination chemoimmunotherapy with or without pre-planned consolidation therapy (radiotherapy, autologous stem cell transplant or immunotherapy)
- Requirement for urgent lymphoma therapy due to tumour-related symptoms, or due to imminent risk of blood vessel, airway, urinary tract, gastrointestinal tract, nerve or spinal cord compression
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Fludarabine30 mg/m^2/day IV for three consecutive days | Drug | atlacabtagene autoleucel CAR T-cells |
| Cyclophosphamide500 mg/m^2/day IV for three consecutive days | Drug | atlacabtagene autoleucel CAR T-cells |
| WZTL-002 CAR T-cellsAlso: 1928T2z CAR T-cellsWZTL-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. | Biological | atlacabtagene autoleucel CAR T-cells |
Primary outcome
Complete response (CR) rate per Investigator assessment
Time frame: 3 months after atlacabtagene autoleucel administration
Investigator-assessed CR rate according to Lugano Response Criteria
Immune effector cell-associated neurotoxicity syndrome (ICANS) rate
Time frame: 3 months after atlacabtagene autoleucel administration
Proportion of participants with ICANS (any grade) as assessed by American Society for Transplantation and Cellular Therapy (ASTCT) criteria
8 secondary outcomes
Complete response (CR) rate per central assessment
Time frame: 3 months after atlacabtagene autoleucel administration
Objective response rate (ORR) per investigator and per central assessment
Time frame: At 3 and at 6 months after atlacabtagene autoleucel administration
Progression free survival (PFS), Event-free survival (EFS), Overall survival (OS) and Duration of Response (DOR)
Time frame: At Months 3, 6, 9, 12, 18, and 24 after atlacabtagene autoleucel administration
Cytokine release syndrome (CRS) rate and grade
Time frame: 3 months after atlacabtagene autoleucel administration
Number and severity of adverse effects
Time frame: From screening until 24 months after atlacabtagene autoleucel administration
Hospitalisation (inpatient) days
Time frame: 3 months after atlacabtagene autoleucel 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)
Time frame: Upto 24 months after atlacabtagene autoleucel administration
European Quality of Life 5-Dimensions 5-Levels Health Questionnaire (EQ-5D-5L)
Time frame: Upto 24 months after atlacabtagene autoleucel administration
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Aug 2026.
- Individual participant dataSharing planned: No
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High Grade B-Cell Lymphoma With MYC and BCL6 Rearrangements, Recurrent Diffuse Large B-Cell Lymphoma
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Philip George, MBChB principal investigator
Te Whatu Ora Health New Zealand, Capital Coast & Hutt Valley
Robert Weinkove, PhD study chair
Malaghan Institute of Medical Research
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Fludarabine, Cyclophosphamide and WZTL-002 CAR T-cells in people with Large B-cell Lymphoma and Diffuse Large B-Cell Lymphoma, Not Otherwise Specified, run by Malaghan Institute of Medical Research at 3 sites in New Zealand.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 47 inclusion and 40 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 7 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in New Zealand. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Brittany Lavender (+64 4 499 6914, clinicaltrialmanagement@malaghan.org.nz), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Complete response (CR) rate per Investigator assessment (time frame: 3 months after atlacabtagene autoleucel administration). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Aug 2026.