ENABLE (Engaging Toll-like Receptor Signalling for B-cell Lymphoma Chimeric Antigen Receptor Therapy)

• Status: Recruiting
• Trial end date: 2026-08-01
• Target enrollment: 0
• Participant gender: All

Summary

This Phase 1, single centre, open label dose escalation study aims to identify a safe dose of third-generation anti-CD19 CAR T-cells (WZTL-002) in the treatment of patients with relapsed or refractory (r/r) B-cell Non Hodgkin Lymphoma, for use in further efficacy trials.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Malaghan Institute of Medical Research
• Collaborators: Wellington Zhaotai Therapies Limited; Wellington Zhaotai Therapies Limited (WZTL)
• Treatments: Cyclophosphamide; Fludarabine; Fludarabine phosphate

Criteria

Inclusion Criteria:

• Age 16 to 75 years (inclusive)

• Biopsy-proven relapsed or treatment refractory aggressive B-cell non-Hodgkin lymphoma of the following subtypes per World Health Organisation (WHO) classification: DLBCL and its variants, PMBCL, tFL, FL, MCL

• Requirement for treatment in the opinion of the investigator

• No other curative treatments available, or not suitable due to patient or disease characteristics or lack of stem cell donor

• Malignancy documented to express CD19 based on flow cytometric or immunohistochemical staining

• Provision of written informed consent for this study

• Life-expectancy from non-lymphoma related causes of > 12 months

• European Cooperative Oncology Group (ECOG) performance status of 0 to 2 inclusive

• Adequate haematologic function, defined by neutrophils ≥ 1.0 × 10^9/L and platelets ≥ 50 × 10^9/L

• No serious cardiac, pulmonary, hepatic or renal disease.

• Serum bilirubin < 2.5 times Upper limit of normal (ULN)

• Estimated creatinine clearance (CrCl) ≥ 50 mL/min using the modified Cockroft Gault estimation or as assessed by direct measurement

• Cardiac Ejection Fraction ≥ 50% as determined by Echocardiogram or MUGA Scan

• Oxygen saturations > 92% on room air

• Diffuse Capacity of the lungs for carbon monoxide (DLCO) or Carbon monoxide transfer coefficient (KCO), Forced expiratory volume in one second (FEV1) and Forced Vital Capacity (FVC) are all ≥ 50% of predicted by spirometry after correcting for haemoglobin and/or volume on lung function testing.

Exclusion Criteria:

• Confirmed active or prior central nervous system (CNS) involvement by lymphoma. In patients with a clinical suspicion of CNS disease, lumbar puncture and MRI brain must be performed

• 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

• Richter Syndrome

• Active autoimmune disease requiring systemic immunosuppression

• Prior solid organ transplantation

• Allogeneic stem cell transplantation within the preceding three months or still requiring systemic immunosuppression

• Current grade II - IV acute graft versus host disease (GVHD), any prior grade IV acute GVHD, or current moderate or severe chronic GVHD

• Need for systemic corticosteroids to treat a condition other than B-NHL at a daily dose of ≥ 10 mg prednisone (or equivalent)

• Peripheral blood lymphocytes < 0.5 x 10^9/L as assessed by complete blood count

• Peripheral blood CD3+ T cells < 350/μL as assessed by lymphocyte subset analysis

• Pregnant or lactating female

• Women of child-bearing potential who are not willing to use highly effective methods of contraception during study participation and for at least 1 year after WZTL-002 administration

• Men who are not willing to use highly effective methods of contraception during study participation and for at least 1 year after WZTL-002 administration

• Men who have a pregnant partner and are not willing to use a condom while performing sexual activity during study participation and for at least 3 months after WZTL-002 administration

• Participants with known sensitivity to immunoglobulin or to components of the investigational product (IP)

• History of active malignancy other than B-cell malignancy within two years prior to enrolment, with the exception of: adequately treated in situ carcinoma of the cervix; adequately treated basal cell carcinoma (BCC) or localized squamous cell carcinoma (SCC) of the skin; other localised malignancy surgically resected (or radically treated with another treatment modality) with curative intent

• Current or prior human immunodeficiency virus (HIV) infection

• Vaccination with a live virus within the preceding four weeks

• Treatment with a purine analogue within the preceding four weeks

• Treatment with alemtuzumab within the preceding 12 weeks

• Prior gene therapy, including prior anti-CD19 chimeric antigen receptor T-cell therapy

• Receipt of an investigational medicine within another clinical trial within the preceding four weeks

• Inadequately controlled systemic infection

• Serologic status reflecting active viral hepatitis B or any history of 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 (< 20 IU), and if they are willing to receive appropriate anti-viral prophylaxis.

• Presence of hepatitis C virus (HCV) antibody

• Presence of New York Heart Association (NYHA) class 2 or higher cardiac symptoms not related to lymphoma

• Significant concomitant illnesses which would in the investigator's opinion make the patient an unsuitable candidate for the trial

• Participants who have diminished capacity or any circumstance that would prohibit them from understanding and providing informed consent in accordance with ICH-GCP (International Conference on Harmonisation, Good Clinical Practice)

• Participant does not provide consent to enrol onto International Cellular Therapy Registry