PD-1 Knockout Engineered T Cells for Advanced Esophageal Cancer

NCT ID: NCT03081715

Last Updated: 2019-06-12

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

16 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-03-14

Study Completion Date

2018-02-28

Brief Summary

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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

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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.

Conditions

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Esophageal Cancer

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

open-label

Study Groups

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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.

Group Type EXPERIMENTAL

PD-1 Knockout T Cells

Intervention Type OTHER

Programmed cell death 1(PD-1) gene will be knocked out by CRISPR Cas9

Interventions

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PD-1 Knockout T Cells

Programmed cell death 1(PD-1) gene will be knocked out by CRISPR Cas9

Intervention Type OTHER

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Anhui Kedgene Biotechnology Co.,Ltd

UNKNOWN

Sponsor Role collaborator

Hangzhou Cancer Hospital

OTHER

Sponsor Role lead

Responsible Party

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Shixiu Wu

Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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shixiu wu, Professor

Role: PRINCIPAL_INVESTIGATOR

Hangzhou Cancer Hospital

Locations

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Hangzhou Cancer Hospital

Hangzhou, Zhejiang, China

Site Status

Countries

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China

References

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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.

Reference Type BACKGROUND
PMID: 24486104 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 25838374 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 25860605 (View on PubMed)

Other Identifiers

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HangzhouCH07

Identifier Type: -

Identifier Source: org_study_id

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