Trial purpose
Cancer treatment
Tumor type
Multi-Cancer
Age
18+
Clinical summary
Summary
This study will test the safety, tolerability and effectiveness of an experimental treatment called “LeY CAR-T cell therapyâ€Âin treating solid tumours that carry the Lewis Y marker. Who is it for? You may be eligible to join this study if you are aged 18 years or above and have an advanced solid tumour that is positive for the Lewis Y antigen. Study details The Lewis Y antigen is a molecule that coats the surface of a cancer cell and is not usually detected by T-cells. The “LeY CAR-T cell therapy†may help the T-cells to find and destroy the cancer cells more easily. In this study, the T-cells will first be collected using a procedure called “Apheresis†that takes part before the study treatment. Apheresis collects some of the white blood cells (also called Leukocytes) including T-Cells from the blood. The collected T-cells will then be modified in the laboratory by a viral vector, to specifically target the cancer cells that have the Lewis Y marker on their surface. After T-cells have been modified, the viral vector will be separated from modified T-cells and removed. Modified T-cells can now be called CAR-T cells. The finished LeY CAR-T cells will then be infused back into the body, without the viral vector. As well as the LeY CAR-T cell therapy, patients will receive by lymphodepleting conditioning chemotherapy as intravenous fludarabine for 2 consecutive days prior to cell infusion to increase immunosuppression and improve persistence of engineered T-cells. LeY CAR-T cell therapy is an experimental treatment. This means that it is not an approved treatment for LeY expressing solid tumours in Australia.
Conditions
This trial is treating people with solid cancers that express the LeY gene (excluding blood cancer)
Eligibility
Inclusion
All of the following must apply at the time of enrollment:
-
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.
- Patient is ≥18 years of age.
- Patient has an ECOG performance status of 0 - 1
- Patient has provided written confirmation of informed consent on participant information and consent form
- Life expectancy of ≥ 12 weeks
-
Patient has adequate organ function satisfying all of the following:
- Patient is deemed capable and willing to undergo the planned study procedures in the view of the principal investigator.
- 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.
- Patient has measurable disease as per RECIST 1.1.
Exclusion
Patients who meet any of the following criteria will be excluded from participation in this study:
- Patients with known active central nervous system (CNS) involvement by malignancy. Patients with previous treated and/or neurologically stable disease will be eligible.
- Prior chimeric antigen receptor T (CART) cell therapy
- 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.
- 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.
- Patient who are eligible for potentially curative therapy
- Uncontrolled active or latent Hepatitis B or active Hepatitis C or HIV
- Patients with uncontrolled systemic fungal, bacterial, viral or other infection despite appropriate antibiotics.
- History or presence of active clinically relevant CNS pathology such as epilepsy, aphasia, severe brain injury, dementia, Parkinson's disease, cerebellar disease or psychosis.
- Radiation therapy within 2 weeks prior to registration
- Patient has an active haematologic malignancy (any lymphoma, leukaemia, multiple myeloma or myelodysplastic syndrome)
- Patient has a history of significant pulmonary disease (including radiation pneumonitis) or known, biopsy proven autoimmune inflammatory disease of the gastrointestinal tract.
- Unstable angina or myocardial infarct within 6 months prior to screening.
- Patient has known clinically significant autoimmune disease with positive serology for RHF (>20kU/L) or ANA (titre >1:40).
- 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.
- Women who are pregnant or breastfeeding.
- 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.
- Patient has a serious uncontrolled medical disorder, psychological or social factors that which would impair the ability to receive protocol therapy and follow up.
Inclusion
- Your cancer has spread to other parts of the body (metastatic) or has grown into nearby parts of the body (locally advanced).
Exclusion
- You have been diagnosed with a prior or secondary type of cancer.
- You have certain types of non-cancer medical conditions.
- You have had certain treatments, surgical procedures or drugs.
Clinical trials have complex eligibility criteria, and other criteria may apply for this trial. Ask your doctor about whether this trial could be right for you.
More information
Trial Identifiers
Information on this page is partially produced from ANZCTR, ClinicalTrials.gov *. View further details about this trial on the registry via the links below:
Trial sponsor
Johnson & Johnson Pharmaceutical Research & Development
Scientific Title
A phase I study investigating the safety and tolerability of an infusion of T lymphocytes transduced with an anti-Lewis Y (LeY) chimeric receptor gene in patients with LeY expressing solid tumours
Get Support
You might find it helpful to speak to someone who has 'been there before'. Our Peer Connect program can provide one-on-one phone support from someone who understands what you're going through and has clinical trials experience.
Know more about Peer Connect
If you need cancer information and practical support for yourself, a carer, family or friend, contact Cancer Council to speak with an experienced health professional on 13 11 20.
Get support
Learn more about clinical trials through this collection of resources in languages other than English.
View information