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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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03081715
Recruitment Status : Recruiting
First Posted : March 16, 2017
Last Update Posted : December 19, 2017
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 samples will also be collected for research purposes.

Condition or disease Intervention/treatment Phase
Esophageal Cancer Other: PD-1 Knockout T Cells Phase 2

Detailed Description:
This is a phase Ⅱ clinical study of ex-vivo knocked-out, expanded, and selected PD-1 knockout-T cells from autologous origin. 21 advanced esophageal cancer patients are planned to receive two cycles of PD-1 knockout engineered T cells treatment. Biomarkers and immunological markers are collected and analyzed as well.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 21 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Masking Description: open-label
Primary Purpose: Treatment
Official Title: A Phase II Trial of PD-1 Knockout Engineered T Cells for the Treatment of Advanced Esophageal Cancer
Actual Study Start Date : March 20, 2017
Estimated Primary Completion Date : February 27, 2018
Estimated Study Completion Date : December 30, 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 protein 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 infused back into patients. To avoid allergic reactions, 50 mg hydrocortisone was intramuscularly injected into patient 30 min before cells infusion every time. Best supportive care was also provided for patients.

A total of 5.0 x 10^8/kg PD-1 Knockout T cells will be infused in one cycle. Patients continued receiving treatment unless they had unacceptable adverse effects, or progressive disease confirmed by CT and PET-CT or they withdrew consent.

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

Primary Outcome Measures :
  1. Incidence of Treatment-Emergent Adverse Events [ Time Frame: 6 months ]
    Number of participants with Adverse Events and/or Dose Limiting Toxicities as a Measure of Safety and tolerability of dose of PD-1 Knockout T cells using Common Terminology Criteria for Adverse Events (CTCAE v3.0) in patients

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

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 circulating tumor DNA [ Time Frame: 6 weeks ]
    Peripheral circuiting tumor DNA is collected at baseline and 6 weeks after last treatment

  4. Temporal Interleukin-2 change in the peripheral blood [ Time Frame: Baseline and 1 month and 3 months ]
    Baseline and 1 month and 3 months Interleukin-2 level in blood

  5. Temporal Interferon-γ change in the peripheral blood [ Time Frame: Baseline and 1 month and 3 months ]
    Baseline and 1 month and 3 months Interferon-γ level in blood

  6. Temporal tumour necrosis factor-α change in the peripheral blood [ Time Frame: Baseline and 1 month and 3 months ]
    Baseline and 1 month and 3 months tumour necrosis factor-α level in blood

  7. Temporal Interleukin-6 change in the peripheral blood [ Time Frame: Baseline and 1 month and 3 months ]
    Baseline and 1 month and 3 months Interleukin-6 level in blood

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Histologically confirmed recurrent or metastatic esophageal cancer
  • Measurable disease
  • Progressed after all standard treatment
  • ECOG performance status of 0-2
  • Expected life span: >= 3 months
  • Toxicities from prior treatment has resolved. Washout period is 4 weeks for chemotherapy, and 2 weeks for targeted therapy
  • 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 identifier (NCT number): NCT03081715

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Contact: shixiu wu, Professor +86-577-56006060

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China, Zhejiang
Hangzhou Cancer Hospital Recruiting
Hangzhou, Zhejiang, China, 310002
Contact: Shixiu Wu, MD    +8657186826086   
Sponsors and Collaborators
Hangzhou Cancer Hospital
Anhui Kedgene Biotechnology Co.,Ltd
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Principal Investigator: shixiu wu, Professor Hangzhou Cancer Hospital

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Responsible Party: Shixiu Wu, Professor, Hangzhou Cancer Hospital Identifier: NCT03081715     History of Changes
Other Study ID Numbers: HangzhouCH07
First Posted: March 16, 2017    Key Record Dates
Last Update Posted: December 19, 2017
Last Verified: December 2017
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
autologous cell infusion

Additional relevant MeSH terms:
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Esophageal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Head and Neck Neoplasms
Digestive System Diseases
Esophageal Diseases
Gastrointestinal Diseases