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PD-1 Knockout Engineered T Cells for Advanced Esophageal Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03081715
Recruitment Status : Completed
First Posted : March 16, 2017
Last Update Posted : June 12, 2019
Sponsor:
Collaborator:
Anhui Kedgene Biotechnology Co.,Ltd
Information provided by (Responsible Party):
Shixiu Wu, Hangzhou Cancer Hospital

Brief Summary:
This study will evaluate the safety of PD-1 knockout engineered T cells in treating advanced esophageal cancer. Blood or tissue samples will also be collected for research purposes.

Condition or disease Intervention/treatment Phase
Esophageal Cancer Other: PD-1 Knockout T Cells Not Applicable

Detailed Description:
This is a prospective clinical study of ex-vivo selected, engineered, and expanded PD-1 knockout T cells from autologous origin. 16 advanced esophageal cancer patients are planned to receive two cycles of PD-1 knockout engineered T cells infusion. Immunological markers are analyzed as well.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 16 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Masking Description: open-label
Primary Purpose: Treatment
Official Title: Safety and Activity of Programmed Cell Death-1 Knockout Engineered T Cells in Patients With Previously Treated Advanced Esophageal Squamous Cell Carcinoma: An Open-label, Single-arm Phase 1 Study
Actual Study Start Date : March 14, 2017
Actual Primary Completion Date : January 23, 2018
Actual Study Completion Date : February 28, 2018

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Experimental Group

Peripheral blood lymphocytes will be collected and Programmed cell death 1(PD-1) gene will be knocked out by CRISPR Cas9 in the laboratory (PD-1 Knockout T cells). The lymphocytes will be selected and expanded ex vivo and reinfused back into patients. To avoid allergic reactions, 50 mg hydrocortisone was intravenously injected into the patient 30 min before cells infusion every time. Best supportive care was also provided for patients.

A total of 1 to 10 x 10^9 PD-1 Knockout T cells will be infused each cycle. Patients continued receiving treatment unless they had unacceptable adverse effects, or progressive disease confirmed by CT or they withdrew consent.

Other: PD-1 Knockout T Cells
Programmed cell death 1(PD-1) gene will be knocked out by CRISPR Cas9




Primary Outcome Measures :
  1. Response Rate [ Time Frame: 1-3 months ]
    Response will be evaluated according to RECIST v1.1


Secondary Outcome Measures :
  1. Incidence of Treatment-Emergent Adverse Events [ Time Frame: 6 months ]
    Number of participants with Adverse Events and grade as a measure of safety and tolerability of PD-1 knockout T cells using CTCAE v4.03


Other Outcome Measures:
  1. Progression free survival (PFS) [ Time Frame: 1 year ]
    From date of randomization until the date of first documented progression or date of death from any cause

  2. Overall Survival (OS) [ Time Frame: 1 year ]
    The time from randomization to death from any cause

  3. Peripheral blood T lymphocyte subsets [ Time Frame: 6 weeks ]
    Sera were collected at baseline and after the first cycle to measure T lymphocyte subsets with flow cytometry

  4. Tumor-infiltrating T cells [ Time Frame: Baseline and after treatment ]
    Baseline and post-treatment tissue samples were tested for the tumor-infiltrating T cells with immunofluorescence.



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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically confirmed recurrent or metastatic esophageal cancer
  • Measurable disease
  • Progressed after standard treatments
  • ECOG performance status of 0-2
  • Expected life span: >= 3 months
  • Toxicities from prior treatment has resolved or ≤ grade 1
  • Major organs function normally
  • Women at pregnant ages should be under contraception
  • Willing and able to provide informed consent

Exclusion Criteria:

  • Other malignancy within 5 years prior to entry into the study, expect for treated non-melanoma skin cancer and cervical carcinoma in situ
  • Poor vasculature
  • Disease to the central nervous system
  • Blood-borne infectious disease, e.g. hepatitis B
  • History of mandatory custody because of psychosis or other psychological disease inappropriate for treatment deemed by treating physician
  • With other immune diseases, or chronic use of immunosuppressants or steroids
  • Pregnancy (women of childbearing potential:Refusal or inability to use effective means of contraception)
  • Breastfeeding
  • Decision of unsuitableness by principal investigator or physician-in-charge

Information from the National Library of Medicine

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): NCT03081715


Locations
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China, Zhejiang
Hangzhou Cancer Hospital
Hangzhou, Zhejiang, China, 310002
Sponsors and Collaborators
Hangzhou Cancer Hospital
Anhui Kedgene Biotechnology Co.,Ltd
Investigators
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Principal Investigator: shixiu wu, Professor Hangzhou Cancer Hospital

Publications:
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Responsible Party: Shixiu Wu, Professor, Hangzhou Cancer Hospital
ClinicalTrials.gov Identifier: NCT03081715     History of Changes
Other Study ID Numbers: HangzhouCH07
First Posted: March 16, 2017    Key Record Dates
Last Update Posted: June 12, 2019
Last Verified: June 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Shixiu Wu, Hangzhou Cancer Hospital:
esophageal cancer
immune checkpoint
PD-1
CRISPER
autologous cell infusion
Additional relevant MeSH terms:
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Esophageal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Head and Neck Neoplasms
Digestive System Diseases
Esophageal Diseases
Gastrointestinal Diseases