Phase I Trial: T4 Immunotherapy of Head and Neck Cancer
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|ClinicalTrials.gov Identifier: NCT01818323|
Recruitment Status : Recruiting
First Posted : March 26, 2013
Last Update Posted : April 6, 2022
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.
|Condition or disease||Intervention/treatment||Phase|
|Head and Neck Cancer||Other: Intra-tumoral T4 immunotherapy||Phase 1|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||30 participants|
|Intervention Model:||Single Group Assignment|
|Intervention Model Description:||
In this dose escalation study, the intervention consists of intratumoral delivery of panErbB-specific CAR T cells, administered alone or following lymphodepleting chemotherapy with fludarabine and cyclophosphamide. In cohort 7, patients will also receive 3 doses of Nivolumab, the first of which is administered 24h before CAR T-cells
This note has been added in response to the warning " WARNING: Phase 1/Phase 2 studies typically have at least one Intervention Type of Drug, Biological/Vaccine or Combination Product."
|Masking:||None (Open Label)|
|Masking Description:||Open label|
|Official Title:||Phase I Trial: T4 Immunotherapy of Head and Neck Cancer|
|Study Start Date :||June 2015|
|Estimated Primary Completion Date :||December 2023|
|Estimated Study Completion Date :||December 2023|
Experimental: Intra-tumoral T4 immunotherapy
Treatment arms comprise escalating doses of T4 immunotherapy, administered alone or in combination with lymph-depleting chemotherapy
Other: Intra-tumoral T4 immunotherapy
Intra-tumoral administration of a single dose of T4-positive patient-derived T-cells (at five escalating dose levels) contained within 1-4 mL. Cohort 6 patients receive CAR T-cells (dose level 3) after lymphodepletion with fludarabine and cyclophosphamide
Other Name: 4ab T1E28z positive T-cells
- 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 ]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 ]
- 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 ]
- 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 ]
- To investigate tumour ErbB receptor phenotype, before and after administration of T4 immunotherapy [ Time Frame: up to 6 weeks post T4 administration ]
- To investigate immunomodulatory effects of metronomic cyclophosphamide on T4 immunotherapy [ Time Frame: up to 6 weeks post T4 administration ]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 ]ELISPOT will be performed on blood samples taken 3 days prior and 29 days after T4 administration to measure for MAGE-reactive T-cells.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01818323
|Contact: John Maher, MD PhD||(+44) 02071881468 ext email@example.com|
|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|