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PD-1 Knockout Engineered T Cells for Advanced Esophageal Cancer

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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

Tracking Information
First Submitted Date  ICMJE March 11, 2017
First Posted Date  ICMJE March 16, 2017
Last Update Posted Date June 12, 2019
Actual Study Start Date  ICMJE March 14, 2017
Actual Primary Completion Date January 23, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 10, 2019)
Response Rate [ Time Frame: 1-3 months ]
Response will be evaluated according to RECIST v1.1
Original Primary Outcome Measures  ICMJE
 (submitted: March 11, 2017)
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
Change History Complete list of historical versions of study NCT03081715 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: June 10, 2019)
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
Original Secondary Outcome Measures  ICMJE
 (submitted: March 11, 2017)
Response Rate [ Time Frame: 3 months ]
Response will be evaluated according to RECIST v1.1
Current Other Pre-specified Outcome Measures
 (submitted: June 10, 2019)
  • 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
  • Overall Survival (OS) [ Time Frame: 1 year ]
    The time from randomization to death from any cause
  • 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
  • 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.
Original Other Pre-specified Outcome Measures
 (submitted: March 11, 2017)
  • 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
  • Overall Survival (OS) [ Time Frame: 1 year ]
    The time from randomization to death from any cause
  • Peripheral blood circulating tumor DNA [ Time Frame: 6 weeks ]
    Peripheral circuiting tumor DNA is collected at baseline and 6 weeks after last treatment
  • 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
  • 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
  • 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
  • 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
 
Descriptive Information
Brief Title  ICMJE PD-1 Knockout Engineered T Cells for Advanced Esophageal Cancer
Official Title  ICMJE 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
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.
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Masking Description:
open-label
Primary Purpose: Treatment
Condition  ICMJE Esophageal Cancer
Intervention  ICMJE Other: PD-1 Knockout T Cells
Programmed cell death 1(PD-1) gene will be knocked out by CRISPR Cas9
Study Arms  ICMJE 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.

Intervention: Other: PD-1 Knockout T Cells
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: June 10, 2019)
16
Original Estimated Enrollment  ICMJE
 (submitted: March 11, 2017)
21
Actual Study Completion Date  ICMJE February 28, 2018
Actual Primary Completion Date January 23, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 80 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE China
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03081715
Other Study ID Numbers  ICMJE HangzhouCH07
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Shixiu Wu, Hangzhou Cancer Hospital
Study Sponsor  ICMJE Hangzhou Cancer Hospital
Collaborators  ICMJE Anhui Kedgene Biotechnology Co.,Ltd
Investigators  ICMJE
Principal Investigator: shixiu wu, Professor Hangzhou Cancer Hospital
PRS Account Hangzhou Cancer Hospital
Verification Date June 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP