Phase I Trial: T4 Immunotherapy of Head and Neck Cancer
The overall goal of this study is to investigate the safety of T4 immunotherapy when administered to treat loco-regional disease in Squamous Cell Cancer of the Head and Neck (SCCHN) that is not suitable for conventional active therapy.
The investigators propose to conduct an open-labelled, non-randomized, dose-escalation phase I trial in which autologous T4+ T-cells are administered to patients with SCCHN. T-cells will be engineered to express a second generation chimeric antigen receptor (CAR) named T1E28z. Engineered T-cells will be injected directly into the tumour site. Patients will not be lymphodepleted. A classical 3+3 design will be employed, with dose escalation from 10^7 through to 10^9 transduced T4+ T-cells, dependent upon toxicity monitoring. It is anticipated that up to 30 patients will be enrolled over the course of the study.
|Study Design:||Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
|Official Title:||Phase I Trial: T4 Immunotherapy of Head and Neck Cancer|
- Dose limiting toxicities for T4 immunotherapy in SCCHN and determine a safe and feasible recommended dose for phase II testing of intra-tumoral T4 immunotherapy. [ Time Frame: Up to 6 weeks post T4 administration ] [ Designated as safety issue: Yes ]Patients will be monitored intensely for the first 24 hours post T4 administration. Patients will the be assessed for signs of toxicity on days 3-4, 5-7, 8, 15, 29 and 43.
- To investigate serum cytokine levels after administration of T4 immunotherapy [ Time Frame: up to 6 weeks post T4 administration ] [ Designated as safety issue: Yes ]
- To investigate persistence of T4+ T-cells at the site of administration and in the peripheral circulation [ Time Frame: up to 6 weeks post T4 administration ] [ Designated as safety issue: Yes ]
- To achieve preliminary assessment of anti-tumour activity, using cross-sectional imaging to quantify objective responses [ Time Frame: up to 6 weeks post T4 administration ] [ Designated as safety issue: No ]
- To investigate tumour ErbB receptor phenotype, before and after administration of T4 immunotherapy [ Time Frame: up to 6 weeks post T4 administration ] [ Designated as safety issue: No ]
- To investigate immunomodulatory effects of metronomic cyclophosphamide on T4 immunotherapy [ Time Frame: up to 6 weeks post T4 administration ] [ Designated as safety issue: Yes ]Pre- and post-treatment absolute number of circulating T-regulatory cells will be compared.
- To investigate effect of T4 immunotherapy upon immune reactivity against endogenous tumour antigens [ Time Frame: up to 6 weeks post T4 administration ] [ Designated as safety issue: No ]ELISPOT will be performed on blood samples taken 3 days prior and 29 days after T4 administration to measure for MAGE-reactive T-cells.
|Study Start Date:||June 2015|
|Estimated Study Completion Date:||December 2017|
|Estimated Primary Completion Date:||June 2017 (Final data collection date for primary outcome measure)|
|Experimental: Intra-tumoral T4 immunotherapy||
Other: Intra-tumoral T4 immunotherapy
Intra-tumoral administration of T4-positive patient-derived T-cells contained within 1 mL.
Other Name: 4ab T1E28z positive T-cells
Further information is provided in van Schalkwyk MC, Papa SE, Jeannon JP, Guerrero Urbano T, Spicer JF, Maher J. Design of a phase I clinical trial to evaluate intratumoral delivery of ErbB-targeted chimeric antigen receptor T-cells in locally advanced or recurrent head and neck cancer. Hum Gene Ther Clin Dev. 2013 Sep;24(3):134-42. doi: 10.1089/humc.2013.144. PubMed ID: 24099518
Please refer to this study by its ClinicalTrials.gov identifier: NCT01818323
|Contact: John Maher, MD PhD||(+44) 02071881468 ext firstname.lastname@example.org|
|Clinical Research Facility, Guy's Hospital||Recruiting|
|London, United Kingdom, SE1 9RT|
|Principal Investigator: John Maher|
|Principal Investigator:||John Maher, MD PhD||King's College London|