NCT01795976

Brief Summary

This is a trial of adoptive T cell therapy using the patient's own T cells, genetically engineered to target the tumour associated antigen NY-ESO-1 (New York esophageal squamous cell carcinoma 1). Eligible patients will undergo leukapheresis (a process to remove white blood cells) 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 14 doses of intravenous Interleukin2 (100000 U/kg) from day 0 to day 4. The primary objective of response rate according to Response Evaluation Criteria in Solid Tumours (RECIST) 1.1 criteria will be assessed by CT scans carried out at week 6, week 12 and at 12 weekly intervals thereafter.

Trial Health

57
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Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
2

participants targeted

Target at below P25 for phase_2

Timeline
Completed

Started Oct 2014

Typical duration for phase_2

Geographic Reach
1 country

1 active site

Status
terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

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Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

January 10, 2013

Completed
1 month until next milestone

First Posted

Study publicly available on registry

February 21, 2013

Completed
1.6 years until next milestone

Study Start

First participant enrolled

October 1, 2014

Completed
3.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

November 1, 2017

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

November 1, 2017

Completed
Last Updated

August 7, 2018

Status Verified

August 1, 2018

Enrollment Period

3.1 years

First QC Date

January 10, 2013

Last Update Submit

August 6, 2018

Conditions

Oesophageal Cancer

Keywords

Oesophageal cancer

Outcome Measures

Primary Outcomes (5)

  • Response rate to New York esophageal squamous cell carcinoma (NYESO) T cells

    To evaluate the response rate in Oesophagogastric cancer patients who are New York esophageal squamous cell carcinoma 1 (NY-ESO-1)and Human Leukocyte Antigen serotype "A" serotype group (HLA-A2) positive to adoptive cell therapy targeted to NY-ESO-1.

    6 weeks post treatment

  • Response rate to NYESO T cells

    To evaluate the response rate in Oesophagogastric cancer patients who are NY-ESO-1 and HLA-A2 positive to adoptive cell therapy targeted to NY-ESO-1.

    12 weeks post treatment

  • Response rate to NYESO T cells

    To evaluate the response rate in Oesophagogastric cancer patients who are NY-ESO-1 and HLA-A2 positive to adoptive cell therapy targeted to NY-ESO-1.

    24 weeks post treatment

  • Response rate to NYESO T cells

    To evaluate the response rate in Oesophagogastric cancer patients who are NY-ESO-1 and HLA-A2 positive to adoptive cell therapy targeted to NY-ESO-1.

    36 weeks post treatment

  • Response rate to NYESO T cells

    To evaluate the response rate in Oesophagogastric cancer patients who are NY-ESO-1 and HLA-A2 positive to adoptive cell therapy targeted to NY-ESO-1.

    48 weeks post treatment

Secondary Outcomes (3)

  • Feasibility and tolerability of NY-ESO-1 targeted cell therapy

    Feasibility will be assessed proceed to full therapy (Study day 6).

  • Evaluation of the progression free survival

    Until progression occurs, estimated to be average of 12 months per patient.

  • Feasibility and tolerability of NY-ESO-1 targeted cell therapy

    Tolerability will be assessed for follow-up period, estimated to be average of 12 months per patient.

Other Outcomes (2)

  • modified T-cell survival

    24 weeks post cell infusion

  • Evaluation of Tumour marker responses.

    24 weeks post T-cell infusion

Study Arms (1)

NY-ESO-1 T cells

EXPERIMENTAL

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 Human Leukocyte Antigen serotype "A" serotype group (HLA2) positive. The T cells undergo lentiviral transduction with NY-ESO-1 specific nucleic acid under Good Manufacturing Practice (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 14 doses of intravenous IL-2 at a dose of 100000 units per kg..

Genetic: NY-ESO-1 T cellsDrug: cyclophosphamideDrug: FludarabineBiological: Interleukin 2

Interventions

NY-ESO-1 T cellsGENETIC
NY-ESO-1 T cells
cyclophosphamideDRUG

cyclophosphamide 60mg/kg/day day -7 and day -6

NY-ESO-1 T cells
FludarabineDRUG

Fludarabine given 25mg/m2 day -5 to day -1

NY-ESO-1 T cells
Interleukin 2BIOLOGICAL

Interleukin 2 (IL2) immunotherapy given day 0 to day 6

Also known as: IL2
NY-ESO-1 T cells

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Patients must have histologically confirmed oesophagogastric cancer with confirmed evidence of metastatic disease and to have failed or refused standard therapies.
  • There must be measurable disease
  • Patients may have had any previous systemic therapies provided they are otherwise fit for treatment
  • Age equal to or greater than 18 years
  • World Health Organisation (WHO) performance status of 0 or 1
  • Patients must be HLA-A2 positive
  • Their tumour must stain positive by immunohistochemistry for NY-ESO-1 (either diagnostic or more recent biopsy is acceptable)
  • Life expectancy \>3months
  • Left ventricular ejection fraction (LVEF) \> 50% as measured by ECHO or Multi Gated Acquisition Scan (MUGA)
  • Haematological and biochemical indices:
  • Haemoglobin (Hb) ≥ 8.0 g/dL
  • Neutrophils ≥ 1.0 x 10\*9/L
  • Platelets (Plts) ≥ 100 x 10\*9/L
  • Any of the following abnormal baseline liver function tests:
  • serum bilirubin ≤ 20 mmol/l (ULN)
  • +9 more criteria

You may not qualify if:

  • Those receiving radiotherapy, biological therapy, endocrine therapy, immunotherapy, systemic steroids, or chemotherapy during the previous four weeks (six weeks for nitrosoureas and Mitomycin-C) prior to treatment or during the course of the treatment.
  • All toxic manifestations of previous treatment must have resolved. Exceptions to this are alopecia or certain Grade 1 toxicities, which an investigator considers should not exclude the patient.
  • Participation in any other clinical trial within the previous 30 days or during the course of this treatment.
  • Previous allogeneic transplant.
  • Clinically significant cardiac disease.
  • Patients who are high medical risks because of non-malignant systemic disease, including those with active infection, uncontrolled cardiac or respiratory disease, or other serious medical or psychiatric disorders which in the lead clinicians opinion would not make the patient a good candidate for adoptive T-cell therapy.
  • Concurrent serious infections within the 28 days prior to treatment
  • Current malignancies at other sites, with the exception of adequately treated cone-biopsied in situ carcinoma of the cervix uteri and basal or squamous cell carcinoma of the skin.
  • Patients known or found to be serologically positive for Hepatitis B, C, HIV or Human T cell lymphotropic Virus (HTLV).
  • History of systemic autoimmune disease which could be life-threatening if reactivation occurred( for example hypothyroidism would be permissible, prior rheumatoid arthritis or systemic lupus erythematosus (SLE0 would not).
  • Evidence of Centra Nervous System (CNS) involvement.
  • Patients who are likely to require systemic steroids or other immunosuppressive therapy.
  • Pregnant and lactating women.
  • Radiotherapy to \>25% skeleton.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

The Christie NHS Foundation Trust

Manchester, M20 3EE, United Kingdom

Location

MeSH Terms

Conditions

Esophageal Neoplasms

Interventions

CyclophosphamidefludarabineInterleukin-2

Condition Hierarchy (Ancestors)

Gastrointestinal NeoplasmsDigestive System NeoplasmsNeoplasms by SiteNeoplasmsHead and Neck NeoplasmsDigestive System DiseasesEsophageal DiseasesGastrointestinal Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide MustardsNitrogen Mustard CompoundsMustard CompoundsHydrocarbons, HalogenatedHydrocarbonsOrganic ChemicalsPhosphoramidesOrganophosphorus CompoundsInterleukinsCytokinesIntercellular Signaling Peptides and ProteinsPeptidesAmino Acids, Peptides, and ProteinsLymphokinesProteinsBiological Factors

Study Design

Study Type
interventional
Phase
phase 2
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR INVESTIGATOR
PI Title
Consultant Medical Oncologist

Study Record Dates

First Submitted

January 10, 2013

First Posted

February 21, 2013

Study Start

October 1, 2014

Primary Completion

November 1, 2017

Study Completion

November 1, 2017

Last Updated

August 7, 2018

Record last verified: 2018-08

Locations

GB(1)