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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03851146




Registration number
NCT03851146
Ethics application status
Date submitted
12/02/2019
Date registered
22/02/2019
Date last updated
3/05/2022

Titles & IDs
Public title
A Study of Anti-Lewis Y Chimeric Antigen Receptor-T Cells (LeY-CAR-T) in Patients With Solid Tumours
Scientific title
A Phase I Investigation of the Safety, Tolerability and Immunological Effects of T Lymphocytes Transduced With an Anti-Lewis Y (LeY) Chimeric Antigen Receptor Gene (LeY-CAR-T) in Patients With LeY Antigen Expressing Advanced Solid Tumours
Secondary ID [1] 0 0
ACTRN12616001580460
Secondary ID [2] 0 0
LeYPh1-02
Universal Trial Number (UTN)
Trial acronym
LeY-CAR-T
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Advanced Cancer 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Other - LeY CAR T cells

Experimental: LeY CAR T cells - One arm study consisting of "3 + 3" dose escalation study design (see below) followed by dose expansion phase at determined MTD.

Dose level : Target Number LeY CART cells infused \*

-1 (if needed): 1 x 10e8

1. 2 x 10e8
2. 5 x 10e8
3. 1 x 10e9
4. 5 x 10e9

* Targeted number of LeY CAR T cells (minus 40% acceptance range) for manufacture according toTGA-approved standard protocols

Treatment follows a lymphodepleting, chemotherapy regimen that consists of Fludarabine (25 mg/m2 per day) and Cyclophosphamide (300mg/m2 per day) for 3 consecutive days prior to cell infusion, with chemotherapy completed at least 48 hours before the re-infusion of the LeY CAR T cells.


Treatment: Other: LeY CAR T cells
Autologous peripheral blood T-lymphocytes transduced with the anti-LeY-scFv-CD28-? vector (LeY CAR T cells)
Intervention code [1] 0 0
Treatment: Other
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
The Maximum Tolerated Dose (MTD) of LeY CAR T-cell infusion
Timepoint [1] 0 0
4 weeks
Primary outcome [2] 0 0
The Dose-Limiting Toxicities (DLTs) associated with LeY CAR T-cell infusion
Timepoint [2] 0 0
4 weeks
Secondary outcome [1] 0 0
To assess the Overall Response (OR) to anti-tumour activity of LeY CAR T-cells
Timepoint [1] 0 0
5 years
Secondary outcome [2] 0 0
To assess the Duration of Response (PR) to anti-tumour activity of LeY CAR T-cells
Timepoint [2] 0 0
5 years
Secondary outcome [3] 0 0
To assess the Progression Free Survival (PFS) of patients treated with LeY CAR T-cells
Timepoint [3] 0 0
5 years
Secondary outcome [4] 0 0
To assess the Overall Survival (OS) of patients treated with LeY CAR T-cells
Timepoint [4] 0 0
5 years
Secondary outcome [5] 0 0
To assess persistence of anti-LeY T-cells in peripheral blood
Timepoint [5] 0 0
12 months

Eligibility
Key inclusion criteria
All of the following must apply at the time of enrollment:

1. Patients with an advanced solid tumour (defined as incurable locally advanced or metastatic disease and excluding any haematologic malignancy).

Tumour is positive for Lewis Y expression by immunohistochemistry - defined as a staining of = 10 % of tumour cells positive for LeY expression. For the purposes of tumour screening, where possible the most recently available tumour sample should be utilised. A new biopsy is not mandatory where archival tissue is available, but may be considered.
2. Patient is =18 years of age.
3. Patient has an ECOG performance status of 0 - 1
4. Patient has provided written confirmation of informed consent on participant information and consent form
5. Life expectancy of = 12 weeks
6. Patient has adequate organ function satisfying all of the following:

* Liver: bilirubin <1.5x upper limit of normal (ULN) unless patient has known Gilbert's syndrome;
* AST/ALT =2.5 x ULN except in patients with known liver metastases where AST/ALT=5.0
* Kidney: either serum creatinine <1.5x ULN or creatinine clearance > 50ml/min. Creatinine clearance is either derived using the Cockcroft-Gault formula or may be measured by 24 hour urine collection or nuclear medicine assessment.
* Lung: Adequate pulmonary function defined by SaO2 >91% on room air and = grade I dyspnoea.
* Cardiac: LVEF = 40% as confirmed by echocardiogram or multiple uptake gated acquisition (MUGA)
* Adequate bone marrow reserve as defined as:

* Absolute neutrophil count (ANC) = 1.0 x 10e9/L
* Absolute lymphocyte count = 0.5 x 10e9/L
* Platelets = 100 x 10e9/L
* Haemoglobin >80g/L
* WCC <30 x 10e9/L
7. Patient is deemed capable and willing to undergo the planned study procedures in the view of the principal investigator.
8. Women of childbearing potential (defined as all women physiologically capable of becoming pregnant) and all male participants must agree to use highly effective methods of contraception for one year following LeY CART therapy.
9. Patient has measurable disease as per RECIST 1.1.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Patients who meet any of the following criteria will be excluded from participation in this study:

1. Patients with known active central nervous system (CNS) involvement by malignancy. Patients with previous treated and/or neurologically stable disease will be eligible.
2. Prior chimeric antigen receptor T (CART) cell therapy
3. Patient has been given chemotherapy and/or G-CSF in the last 4 weeks or is planned to receive such therapy prior to apheresis of PBMC. Patients can only receive cytotoxic drugs as per the schedule of treatment for this protocol.
4. Patient has had immunosuppressive therapy within 4 weeks of apheresis. Therapeutic doses of steroids (defined as > 20 mg/day of Prednisolone (or equivalent) must be able to be stopped > 7 days prior to leukapheresis and 72 hours prior to LeY CART cell infusion Physiologic doses of steroid (e.g. Prednisolone <10mg or equivalent), topical and inhaled steroids are permitted.
5. Patient who are eligible for potentially curative therapy
6. Uncontrolled active or latent Hepatitis B or active Hepatitis C or HIV
7. Patients with uncontrolled systemic fungal, bacterial, viral or other infection despite appropriate antibiotics.
8. History or presence of active clinically relevant CNS pathology such as epilepsy, aphasia, severe brain injury, dementia, Parkinson's disease, cerebellar disease or psychosis.
9. Radiation therapy within 2 weeks prior to registration
10. Patient has an active haematologic malignancy (any lymphoma, leukaemia, multiple myeloma or myelodysplastic syndrome)
11. Patient has a history of significant pulmonary disease (including radiation pneumonitis) or known, biopsy proven autoimmune inflammatory disease of the gastrointestinal tract.
12. Unstable angina or myocardial infarct within 6 months prior to screening.
13. Patient has known clinically significant autoimmune disease with positive serology for RHF (>20kU/L) or ANA (titre >1:40).
14. Women of child bearing potential (WOCBP) who are unwilling or unable to use an effective method of contraception to avoid pregnancy for the entire study period and for at least 12 months after completion of study treatment.
15. Women who are pregnant or breastfeeding.
16. Men who are unwilling or unable to use an acceptable method of contraception for the entire study period and for at least 12 months after completion of study treatment if their sexual partners are WOCBP.
17. Patient has a serious uncontrolled medical disorder, psychological or social factors that which would impair the ability to receive protocol therapy and follow up.

Study design
Purpose of the study
Treatment
Allocation to intervention
Not applicable
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
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
24/11/2016
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/04/2022
Sample size
Target
Accrual to date
Final
20
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment postcode(s) [1] 0 0
3000 - Melbourne

Funding & Sponsors
Primary sponsor type
Other
Name
Peter MacCallum Cancer Centre, Australia
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This clinical trial is an open-label, single-centre, phase I study designed to investigate the safety and tolerability of a single infusion of autologous peripheral blood T-lymphocytes transduced with the anti-LeY-scFv-CD28-? vector (LeY CAR T-cells) The primary aim of the trial is to evaluate the safety and tolerability of LeY CAR T cells in patients with Lewis Y antigen-expressing, advanced solid tumours.

The secondary aim of the trial is to assess the anti-tumour activity of LeY CAR T cells in patients with LeY antigen-expressing, advanced solid tumours.

Patients aged 18 years or older with advanced solid tumours have consented to pre-screening that allows their tumours to be assessed for LeY expression by immunohistochemistry. Patients whose tumours test positive for LeY were then able to proceed to eligibility screening and, if found to fulfil the eligibility criteria, were registered in the study. The study involves an initial dose escalation phase followed by an expansion phase.
Trial website
https://clinicaltrials.gov/study/NCT03851146
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Ben Solomon
Address 0 0
Peter MacCallum Cancer Centre, Australia
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT03851146