NCT03851146

A Study of Anti-Lewis Y Chimeric Antigen Receptor-T Cells (LeY-CAR-T) in Patients With Solid Tumours

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

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 20 (actual)
• Sponsor: Peter MacCallum Cancer Centre, Australia · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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-ζ 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.

Detailed description

To autologous peripheral blood T-lymphocytes transduced with the anti-LeY-scFv-CD28-ζ vector in patients with LeY expressing advanced solid tumours. evaluate the safety and tolerability of an intravenous infusion of autologous peripheral blood T-lymphocytes transduced with the anti-LeY-scFv-CD28-ζ vector in patients with LeY expressing advanced solid tumours. Aims: To evaluate the safety and tolerability of an intravenous infusion of autologous peripheral blood T-lymphocytes transduced with the anti-LeY-scFv-CD28-ζ vector in patients with LeY expressing advanced solid tumours. Primary Objectives To determine the maximum tolerated dose and rate of dose limiting toxicities of a single intravenous infusion of autologous peripheral blood T-lymphocytes transduced with the anti-LeY-scFv-CD28-ζ vector in patients with LeY expressing advanced solid tumours (LeY CAR T cells). Secondary Objectives i. To assess the anti-tumour activity of the LeY CAR T cells in terms of overall response, duration of response, progression free survival and overall survival. ii. To assess persistence in peripheral blood of the LeY CAR T cells. The study will recruit an anticipated number of 12 patients in the dose escalation phase consisting of 4 dose levels, each with dose level cohorts of 3 patients. Following completion of the dose-escalation phase, additional patients with Le Y expressing solid tumours will be recruited to the study. These patients will be administered the maximum number of cells safely delivered in the dose escalation phase of the study. A subset comprising 5 patients in the expansion cohort will be administered Indium-111 labelled T-cells and imaged by SPECT to determine the biodistribution of reinfused T cells. If the proposed number of T cells is unable to be obtained due to technical production reasons, the available number will be infused. It is anticipated that up to 30 patients will be treated on this protocol.

Conditions

• Advanced Cancer

Interventions

Type	Name	Description
BIOLOGICAL	LeY CAR T cells	Autologous peripheral blood T-lymphocytes transduced with the anti-LeY-scFv-CD28-ζ vector (LeY CAR T cells)

Timeline

• Start date: 2016-11-24
• Primary completion: 2022-04-01
• Completion: 2022-04-01
• First posted: 2019-02-22
• Last updated: 2022-05-03

Locations

1 site across 1 country: Australia