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New treatment option for Large B-cell Lymphoma
Official title A Study of WZTL-002 CAR T-cells for Adults With Relapsed Large B-cell Lymphoma
ClinicalTrials.gov ID: NCT06486051
What this study is testing
What is Fludarabine?
Fludarabine is an investigational medicine, given as an infusion into a vein, being studied as a potential treatment for large b-cell lymphoma.
Plain-language explanation of the investigational treatment - it is being studied and is not an approved or proven therapy. The study team can confirm the details.
- What it's testing
- 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?
- Phase 2: a mid-size study of how well it works
A plain-language read of the study's public ClinicalTrials.gov listing. The study team confirms the details.
Who can take part
Ages 18 to 75
You may be able to join 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...
- Large B-cell lymphomas of the following histological subtypes:
- Diffuse LBCL, not otherwise specified
You likely can't join if
- Active central nervous system (CNS) involvement by lymphoma. In patients with a history of CNS disease or a clinical suspicion of current CNS...
- Active CNS pathology including: epilepsy, seizure within the preceding year, aphasia, paresis, stroke, dementia, psychosis within the preceding year...
- 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
See the full eligibility criteria
Who can 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
- 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...
- 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...
- 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
What rules you out
- 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...
- 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...
- 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...
- 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...
- 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
The study team makes the final eligibility decision.
Where it's taking place
- Christchurch, Christchurch Central, New Zealand
- Newtown, Wellington Region, New Zealand
- Auckland, New Zealand
Questions & answers
Do participants get paid in this trial?
This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.
Is it free to join, and do I need insurance?
Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.
How long does this study last?
The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.
Who can join this trial?
This study is enrolling all sexes, 18 years to 75 years. The study team makes the final eligibility decision.
Where is this trial taking place?
Study sites include Christchurch, Christchurch Central, New Zealand; Newtown, Wellington Region, New Zealand; Auckland, New Zealand. Enter your location above to see the nearest site and check your eligibility.
Explore other conditions
BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from ClinicalTrials.gov; the study team decides eligibility.