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A Study of Atlacabtagene Autoleucel CAR T-cells for Adults With Relapsed Large B-cell Lymphoma

RecruitingPhase 2Ages 18 Years - 75 YearsAllMalaghan Institute of Medical Research
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In plain words

What the trial is, and whether it could suit you

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 a

Sign in to get the eligibility rules as simple questions to take to your doctor.

📋 Eligibility rules (as published)
Inclusion Criteria: 1. Age 18 to 75 years (inclusive) at the time of informed consent 2. Signed written informed consent for this trial 3. 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 4. 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 5. 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 6. Positron emission tomography (PET) positive disease according to the Lugano 2014 criteria 7. Available tumour tissue (comprising a tissue block or at least 6 unstained slides) for central histological review 8. Lymphoma-related life expectancy at least 12 weeks, and life expectancy related to conditions other than lymphoma at least 12 months 9. ECOG performance status of 0 or 1 10. Adequate haematologic function, defined by: * Neutrophils ≥ 1.0 × 10\^9/L, and Platelets ≥ 75 × 10\^9/L, and * Lymphocytes ≥ 0.3 × 10\^9/L 11. 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. 12. 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. 13. Adequate lung function, defined as ≤ Grade 1 dyspnoea according to NCI CTCAE v5.0, and oxygen saturation (sO2) ≥ 92% on room air. 14. 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. 15. 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 16. 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 17. Participant agrees not to donate blood components at any time after receiving WZTL-002 Exclusion Criteria: 1. 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. 2. 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 3. 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 4. Patient has received 3 or more prior lines of therapy for LBCL, where 1 line of therapy is defined as 1 or more c
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What it tests

  • Fludarabine
  • Cyclophosphamide
  • WZTL-002 CAR T-cells
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Where

3 sites
Auckland City Hospital
Auckland, New Zealand
Christchurch Hospital
Christchurch, New Zealand
Wellington Hospital
Newtown, New Zealand
🤝 Taking part is your choice, and you can leave at any time. Only the trial team can confirm you are eligible — always decide together with your own doctor.
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