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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04049513




Registration number
NCT04049513
Ethics application status
Date submitted
29/07/2019
Date registered
8/08/2019

Titles & IDs
Public title
ENABLE-1 (Engaging Toll-like Receptor Signalling for B-cell Lymphoma Chimeric Antigen Receptor Therapy)
Scientific title
A Phase I Dose Escalation Trial of Autologous Third-generation Anti-CD19 Chimeric Antigen Receptor T-cells (WZTL-002) for Relapsed and Refractory B-cell Lymphomas
Secondary ID [1] 0 0
U1111-1216-2053
Secondary ID [2] 0 0
WZTL002-1
Universal Trial Number (UTN)
Trial acronym
ENABLE-1
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Lymphomas Non-Hodgkin's B-Cell 0 0
Diffuse Large B-cell Lymphoma (DLBCL) 0 0
Primary Mediastinal B-cell Lymphoma (PMBCL) 0 0
Transformed Follicular Lymphoma (TFL) 0 0
Follicular Lymphoma (FL) 0 0
Mantle Cell Lymphoma (MCL) 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Other - WZTL002-1 (1928T2z CAR-T cells)
Treatment: Drugs - Cyclophosphamide and Fludarabine lymphodepleting chemotherapy

Experimental: WZTL002-1 (1928T2z CAR T-cells) - A starting WZTL-002 dose of 5 × 10\^4 CAR T-cells/kg has been selected with four possible dose level cohorts proposed.

Escalation to a higher dose cohort will be based on assessment of dose limiting toxicities to determine safety at a given dose level.


Treatment: Other: WZTL002-1 (1928T2z CAR-T cells)
WZTL-002 comprises autologous third-generation anti-CD19 chimeric antigen receptor T-cells (termed 1928T2z). The chimeric antigen receptor in WZTL-002 incorporates the FMC63 anti-CD19 soluble chain variable fragment extracellularly, and portions of both CD28 and the Toll/interleukin-1 receptor (TIR) domain of Toll Like Receptor 2 (TLR2) as intracellular co-stimulatory domains, alongside CD3?. WZTL-002 (autologous 1928T2z CAR T-cells) will be administered on D0 as a single IV infusion, following lymphodepleting chemotherapy.

Treatment: Drugs: Cyclophosphamide and Fludarabine lymphodepleting chemotherapy
Cyclophosphamide 500 mg/m\^2 IV on days -5 to -3, inclusive. Fludarabine 30 mg/m\^2 IV on days -5 to -3, inclusive
Intervention code [1] 0 0
Treatment: Other
Intervention code [2] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number and severity of adverse events assessed by CTCAE v5.0, except for Cytokine Release Syndrome and Immune Effector Cell-Associated Neurotoxicity Syndrome, which will be assessed by ASTCT consensus grading criteria
Timepoint [1] 0 0
3 months after administration
Secondary outcome [1] 0 0
Feasibility of Manufacture
Timepoint [1] 0 0
3 months after administration
Secondary outcome [2] 0 0
Overall Response Rate
Timepoint [2] 0 0
3 months after administration
Secondary outcome [3] 0 0
Cumulative CR rate
Timepoint [3] 0 0
6 months after administration
Secondary outcome [4] 0 0
Relapse-free survival
Timepoint [4] 0 0
24 months after administration
Secondary outcome [5] 0 0
Overall survival
Timepoint [5] 0 0
24 months after administration
Secondary outcome [6] 0 0
Recommended dose
Timepoint [6] 0 0
3 months after administration

Eligibility
Key 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
* Presence of measurable disease as per Lugano 2014 Criteria
* 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
* Lymphoma-related life expectancy at least 12 weeks, and 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.
Minimum age
16 Years
Maximum age
75 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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
* Systemic corticosteroids at doses of = 20mg prednisone daily or equivalent within 7 days of enrolment
* Peripheral blood lymphocytes < 0.3 x 10^9/L as assessed by complete blood count
* Peripheral blood CD3+ T cells < 150/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
* Cytotoxic chemotherapy, radiotherapy or monoclonal antibody therapy (other than alemtuzumab) within 2 weeks of enrolment
* 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

Study design
Purpose of the study
Treatment
Allocation to intervention
NA
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
11/10/2019
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/03/2029
Actual
Sample size
Target
Accrual to date
Final
30
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 0 0
New Zealand
State/province [1] 0 0
Wellington

Funding & Sponsors
Primary sponsor type
Other
Name
Malaghan Institute of Medical Research
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Wellington Zhaotai Therapies Limited
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Robert Weinkove, MBBS, PhD
Address 0 0
Te Whatu Ora Health New Zealand Capital Coast & Hutt Valley
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Robert Weinkove, MBBS, PhD
Address 0 0
Country 0 0
Phone 0 0
+64 4 918 5117
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
All IPD that underlie results in a publication
When will data be available (start and end dates)?
Available to whom?
Available for what types of analyses?
How or where can data be obtained?


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT04049513