A Study of Anti-Lewis Y Chimeric Antigen Receptor-T Cells (LeY CAR T) in Patients With Solid Tumours
- Conditions
- advanced solid tumors expressing LeY antigenCancer - Other cancer types
- Registration Number
- ACTRN12616001580460
- Lead Sponsor
- Peter MacCallum Cancer Center
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- All
- Target Recruitment
- 21
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 'greater than or equal to'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 'greater than or equal to'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 'greater than or equal to' 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 equal to 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-h 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-Patient is able to undergo apheresis of PBMC within 14 days following registration.
9-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 CAR T therapy.
10-Patient has measurable disease as per RECIST 1.1
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 the last 4 weeks. 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 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
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method To determine the maximum tolerated dose of a single intravenous infusion of autologous peripheral blood T-lymphocytes transduced with the anti-LeY-scFv-CD28-zeta vector in patients with LeY expressing advanced solid tumours (LeY CAR T cells).<br><br>This outcome will be assessed by evaluating occurrence, type, severity and relationship to treatment of adverse events (AEs) and laboratory abnormalities.<br>9Adverse events described according to NCI CTCAE v4.03)[ 28 days after infusion];To determine the rate of dose limiting toxicities of a single intravenous infusion of autologous peripheral blood T-lymphocytes transduced with the anti-LeY-scFv-CD28-zeta vector in patients with LeY expressing advanced solid tumours (LeY CAR T cells).<br><br>This outcome will be assessed by evaluating the occurrence and type of DLTs[ 28 days after infusion]
- Secondary Outcome Measures
Name Time Method