Status:
RECRUITING
A Study of WZTL-002 CAR T-cells for Adults With Relapsed Large B-cell Lymphoma
Lead Sponsor:
Malaghan Institute of Medical Research
Collaborating Sponsors:
BioOra Limited
Wellington Zhaotai Therapies Limited
Conditions:
Large B-cell Lymphoma
Diffuse Large B-Cell Lymphoma, Not Otherwise Specified
Eligibility:
All Genders
18-75 years
Phase:
PHASE2
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 h...
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 ...
Eligibility Criteria
Inclusion
- 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
- 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 WZTL-002, 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 WZTL-002, and
- Agree not to donate sperm for conception, or to provide gametes for in vitro fertilisation for at least 12 months after administration of WZTL-002
- Participant agrees not to donate blood components at any time after receiving WZTL-002
Exclusion
- 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
- 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). Patients with presence of HBcAb, but absence of HBsAg, are eligible if hepatitis B virus (HBV) DNA is undetectable (or is \< 20 IU/mL), and if they are willing to receive 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
Key Trial Info
Start Date :
July 12 2024
Trial Type :
INTERVENTIONAL
Allocation :
ESTIMATED
End Date :
June 30 2028
Estimated Enrollment :
60 Patients enrolled
Trial Details
Trial ID
NCT06486051
Start Date
July 12 2024
End Date
June 30 2028
Last Update
February 14 2025
Active Locations (3)
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1
Christchurch Hospital
Christchurch, Christchurch Central, New Zealand, 8011
2
Wellington Hospital
Newtown, Wellington Region, New Zealand, 6021
3
Auckland City Hospital
Auckland, New Zealand, 1023