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PD-1 Knockout Engineered T Cells for Advanced Esophageal Cancer

Primary Purpose

Esophageal Cancer

Status
Completed
Phase
Not Applicable
Locations
China
Study Type
Interventional
Intervention
PD-1 Knockout T Cells
Sponsored by
Hangzhou Cancer Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Esophageal Cancer focused on measuring esophageal cancer, immune checkpoint, PD-1, CRISPER, autologous cell infusion

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Hangzhou Cancer Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Experimental Group

Arm Description

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.

Outcomes

Primary Outcome Measures

Response Rate
Response will be evaluated according to RECIST v1.1

Secondary Outcome Measures

Incidence of Treatment-Emergent Adverse Events
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

Full Information

First Posted
March 11, 2017
Last Updated
June 10, 2019
Sponsor
Hangzhou Cancer Hospital
Collaborators
Anhui Kedgene Biotechnology Co.,Ltd
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1. Study Identification

Unique Protocol Identification Number
NCT03081715
Brief Title
PD-1 Knockout Engineered T Cells for Advanced Esophageal Cancer
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
Study Type
Interventional

2. Study Status

Record Verification Date
June 2019
Overall Recruitment Status
Completed
Study Start Date
March 14, 2017 (Actual)
Primary Completion Date
January 23, 2018 (Actual)
Study Completion Date
February 28, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Hangzhou Cancer Hospital
Collaborators
Anhui Kedgene Biotechnology Co.,Ltd

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Esophageal Cancer
Keywords
esophageal cancer, immune checkpoint, PD-1, CRISPER, autologous cell infusion

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Masking Description
open-label
Allocation
N/A
Enrollment
16 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Experimental Group
Arm Type
Experimental
Arm Description
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 Type
Other
Intervention Name(s)
PD-1 Knockout T Cells
Intervention Description
Programmed cell death 1(PD-1) gene will be knocked out by CRISPR Cas9
Primary Outcome Measure Information:
Title
Response Rate
Description
Response will be evaluated according to RECIST v1.1
Time Frame
1-3 months
Secondary Outcome Measure Information:
Title
Incidence of Treatment-Emergent Adverse Events
Description
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
Time Frame
6 months
Other Pre-specified Outcome Measures:
Title
Progression free survival (PFS)
Description
From date of randomization until the date of first documented progression or date of death from any cause
Time Frame
1 year
Title
Overall Survival (OS)
Description
The time from randomization to death from any cause
Time Frame
1 year
Title
Peripheral blood T lymphocyte subsets
Description
Sera were collected at baseline and after the first cycle to measure T lymphocyte subsets with flow cytometry
Time Frame
6 weeks
Title
Tumor-infiltrating T cells
Description
Baseline and post-treatment tissue samples were tested for the tumor-infiltrating T cells with immunofluorescence.
Time Frame
Baseline and after treatment

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
shixiu wu, Professor
Organizational Affiliation
Hangzhou Cancer Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hangzhou Cancer Hospital
City
Hangzhou
State/Province
Zhejiang
ZIP/Postal Code
310002
Country
China

12. IPD Sharing Statement

Plan to Share IPD
Undecided
Citations:
PubMed Identifier
24486104
Citation
Niu Y, Shen B, Cui Y, Chen Y, Wang J, Wang L, Kang Y, Zhao X, Si W, Li W, Xiang AP, Zhou J, Guo X, Bi Y, Si C, Hu B, Dong G, Wang H, Zhou Z, Li T, Tan T, Pu X, Wang F, Ji S, Zhou Q, Huang X, Ji W, Sha J. Generation of gene-modified cynomolgus monkey via Cas9/RNA-mediated gene targeting in one-cell embryos. Cell. 2014 Feb 13;156(4):836-43. doi: 10.1016/j.cell.2014.01.027. Epub 2014 Jan 30.
Results Reference
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PubMed Identifier
25838374
Citation
Rosenberg SA, Restifo NP. Adoptive cell transfer as personalized immunotherapy for human cancer. Science. 2015 Apr 3;348(6230):62-8. doi: 10.1126/science.aaa4967.
Results Reference
background
PubMed Identifier
25860605
Citation
Sharma P, Allison JP. Immune checkpoint targeting in cancer therapy: toward combination strategies with curative potential. Cell. 2015 Apr 9;161(2):205-14. doi: 10.1016/j.cell.2015.03.030.
Results Reference
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PD-1 Knockout Engineered T Cells for Advanced Esophageal Cancer

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