Clinical Trial Results:
A Phase II Trial to Assess the Activity of NY-ESO-1 Targeted T Cells in Advanced Oesophagogastric Cancer
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Summary
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EudraCT number |
2012-005327-33 |
Trial protocol |
GB |
Global end of trial date |
30 Nov 2017
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Results information
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Results version number |
v1(current) |
This version publication date |
24 Jun 2023
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First version publication date |
24 Jun 2023
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
CFTSp0603
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01795976 | ||
WHO universal trial number (UTN) |
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Other trial identifiers |
REC REF number: 13/SS/0041, Sponsor number: 12_DOG14_22 | ||
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Sponsors
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Sponsor organisation name |
The Christie NHS FoundationTrust
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Sponsor organisation address |
Wilmslow Road, Manchester, United Kingdom, M20 4BX
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Public contact |
The Christie NHS Foundation Trust, The Christie NHS Foundation Trust, +44 01613067041, Christiesponsoredresearch@christie.nhs.uk
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Scientific contact |
The Christie NHS Foundation Trust, The Christie NHS Foundation Trust, +44 01613067041, Christiesponsoredresearch@christie.nhs.uk
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
30 Nov 2017
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
30 Nov 2017
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Global end of trial reached? |
Yes
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Global end of trial date |
30 Nov 2017
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Was the trial ended prematurely? |
Yes
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General information about the trial
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Main objective of the trial |
Is using the patient's own engineered cells as a therapy effective in treating oesophago-gastric cancer (as an example of a common epithelial malignancy) where there is a clear need for more effective therapies?
Primary objective: To evaluate the response rate in Oesophagogastric cancer patients who are NYESO-1 and HLA-A2 positive to adoptive cell therapy targeted to NYESO-1
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Protection of trial subjects |
Potential subjects will need to have a screening blood test for HLAA0201
positivity prior to consenting to the study,
therefore a second consent form will be required for this proceedure.
Subjects data will be shared amongst study collaborators in the European Union and The United States, where data
protection laws may differ. There will be a statement on the consent form for the patient to agree to this.
There will be 3rd party access to patient data, by Adaptimmune Limited who are providing the vector for the modified Tcells.
This information will be conveyed to the patient via the patient information sheet, and there will be a statement
on the consent form for the patient to agree to this.
Subjects will be receiving a novel therapy, which has limited toxicity data from similar studies performed in the United
States. This information will be conveyed to the patient via the patient information sheet.
Subjects will be receiving more CT scans during the study period then they would as standard of care, therefore they
will recieve a higher radiation dose. A dose and risk assessment wil be performed by a trained radiologist, and this
information will be conveyed to the patient via the patient information sheet.
There is a high risk of Toxicity from the Preconditioning
Chemotherapy and subsequent IL2 therapy. This information
will be conveyed to the patient via the patient information sheet.
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Background therapy |
NY-ESO-1 T cells are T cells engineered to target the tumour antigen NY-ESO-1. Autologous T cells are obtained from eligible patients who have NY-ESO-1 positive tumours and who are HLA-A*0201 positive. The T cells undergo lentiviral transduction with NY-ESO-1 specific nucleic acid under GMP conditions. The patient will then undergo preconditioning chemotherapy with a regime of cyclophosphamide 60mg/kg/day day -7 and -6 followed by fludarabine 25mg/m2 day -5 to -1. They will receive autologous NY-ESO-1 T cells on day 0 and following on from that they will receive up to 12 doses of intravenous IL-2 at a dose of 100,000 units per kg. Due to the risk of toxicities from the preconditioning chemotherapy, such as immune suppression, prophylactic and supportive medication will be administered | ||
Evidence for comparator |
Interleukin-2 (IL2) is a well-accepted component in the treatment regimes of recent adoptive cell therapy trials. It has been shown to promote the survival and proliferation of T cells and has been widely used in experimental cell therapy with LAK cells and TILs (Rosenberg, et al 1993). Cyclophosphamide 60mg/kg/day (Day -7 and -6) and Fludarabine 25mg/m2/day (Day -5 to -1) will be used in this study. This non-myeloablative regime was used in the pilot adoptive T cell therapy study (Rosenberg et al., 2011) and a well-established pre-conditioning chemotherapy regime for adoptive cell therapy studies in recent times. There is considerable justification for the use of pre-conditioning chemotherapy. The T cell dose used in the two NY-ESO-1 T cell studies has been in the range of 1-130 billion cells (1-10 billion in Kalos et al study and 16-130 billion in Robbins et al), both showed good efficacy and tolerance. We have chosen the intermediate dose of 5-50 billion (i.e. 5x109 to 5x1010). This is also based on the realistic estimate of achievable cell production from the experience of our cell production units. | ||
Actual start date of recruitment |
01 May 2014
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
United Kingdom: 2
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Worldwide total number of subjects |
2
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EEA total number of subjects |
2
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
1
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From 65 to 84 years |
1
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85 years and over |
0
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Recruitment
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Recruitment details |
The trial opened to recruitment on 30th September 2014. Patients were recruited from one hospital site in the United Kingdom. All patients gave written informed consent before any trial related procedures were carried out. | ||||||
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Pre-assignment
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Screening details |
Eligible patients have advanced gastro-esophageal malignancies, have received at least one line of prior palliative chemotherapy, are HLA-A*02:01+, and have NY-ESO-1 expression in malignant cells detected by immunohistochemistry (IHC). | ||||||
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Period 1
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Period 1 title |
overall trial (overall period)
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Is this the baseline period? |
Yes | ||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||
Blinding implementation details |
Not Applicable
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Arms
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Arm title
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NY-ESO-1 T-cell treatment | ||||||
Arm description |
This is a single arm trial of adoptive T cell therapy using autologous T cells genetically engineered to target the tumour associated antigen NY-ESO-1. Eligible patients will undergo leukapheresis to retrieve sufficient T cells which will be gene modified and expanded in the laboratory. Patients will undergo preconditioning chemotherapy with cyclophosphamide (60mg/kg) day -7 and day -6, followed by fludarabine (25mg/m2) day -5 to day -1. The NY-ESO-1 gene modified cells will be re-infused on day 0 and the patients will receive up to 12 doses of intravenous IL2 (100,000 U/kg) from day 0 to day 4. Each participant will receive one cycle of treatment only. | ||||||
Arm type |
Single arm | ||||||
Investigational medicinal product name |
autologous primary T-lymphocytes
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
NY-ESO-1 T cells
(5x109 to 5x1010 cells).
Volume: ~270ml
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Investigational medicinal product name |
Cyclophosphamide
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
60mg/kg/day
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Investigational medicinal product name |
Fludarabine
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
25mg/m2/day
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Baseline characteristics reporting groups
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Reporting group title |
overall trial
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Reporting group description |
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End points reporting groups
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Reporting group title |
NY-ESO-1 T-cell treatment
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Reporting group description |
This is a single arm trial of adoptive T cell therapy using autologous T cells genetically engineered to target the tumour associated antigen NY-ESO-1. Eligible patients will undergo leukapheresis to retrieve sufficient T cells which will be gene modified and expanded in the laboratory. Patients will undergo preconditioning chemotherapy with cyclophosphamide (60mg/kg) day -7 and day -6, followed by fludarabine (25mg/m2) day -5 to day -1. The NY-ESO-1 gene modified cells will be re-infused on day 0 and the patients will receive up to 12 doses of intravenous IL2 (100,000 U/kg) from day 0 to day 4. Each participant will receive one cycle of treatment only. | ||
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End point title |
Response rate by RECIST v1.1 in oesophagogastric cancer patients who are NY-ESO-1 and HLA-A*0201 positive to adoptive cell therapy targeted to NY-ESO-1. [1] | ||||||
End point description |
Two patients were infused with NY-ESO-1-specific TCR-T cells as per protocol. Both patients experienced symptoms consistent with cytokine release syndrome in the first two weeks post infusion, which resolved with supportive regimens. Whilst Patient 1 recovered, Patient 2 subsequently developed enterocolitis and bone marrow failure from which was fatal, despite immunosuppressive therapy. Immunological assays detected outgrowth in the peripheral blood and tissues of T cell clones. Notably the dominant clone was not associated with the transduced NY-ESO-1 TCR.
Both patients achieved stable disease as best response. Patient 1 maintained disease stability until month 7 post infusion. Patient 2 demonstrated a 23% reduction in target lesions on imaging at 4 weeks post infusion. At week 6 this had reduced to 10%.
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End point type |
Primary
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End point timeframe |
Baseline to end of study
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: This is a single arm study and no comparison has been made. This study was terminated early and descriptive statistics only has been performed. |
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Adverse events information
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Timeframe for reporting adverse events |
From Baseline until End of Trial.
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Assessment type |
Non-systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
19.0
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Reporting groups
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Reporting group title |
NY-ESO-1
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Reporting group description |
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||||||
Date |
Amendment |
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25 Mar 2014 |
Substantial amendment 2
Simplify the inclusion criteria parameters for ALT and AST. The patient information sheet and consent form has been amended in order to clarify that anonomysed trial data will be sent to a subsidiary of the trial vector supplier Adaptimmune. |
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26 Sep 2014 |
Substantial amendment 3
The Protocol has been amended to incorporate changes requested by the Swedish regulatory authority, as part of the trial authorisation submission there. The version of the protocol approved in Sweden alone is version 5, and has been provided for reference.
There has been a change in Chief Investigator for the trial, with Dr Fiona Thistlethwaite returning to the position, replacing Dr Was Mansoor. This change, along with the changes requested by the Swedish regulator is incorporated into version 6 of the protocol.
The Investigator’s Brochure has had a number of changes requested by the Swedish regulatory authority, as part of the trial authorisation submission there. There has also been updated information provided by the vector supplier Adaptimmune.
The Main Study Patient Information Sheet and Consent Form has been amended as anonymised trial data will now be being sent to GSK as well as the trial vector supplier Adaptimmune. Adaptimmune have entered into a strategic collaboration and licensing agreement with GlaxoSmithKline (GSK)
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Interruptions (globally) |
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| Were there any global interruptions to the trial? Yes | |||||||
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Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||||||
| None reported | |||||||
