PD-1 Knockout Engineered T Cells for Advanced Esophageal Cancer

Esophageal Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03081715
• Other study ID #: HangzhouCH07
• Status: Completed
• Phase: N/A
• Start date: March 14, 2017
• Est. completion date: February 28, 2018

Study information

• Verified date: June 2019
• Source: Hangzhou Cancer Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 16
• Est. completion date: February 28, 2018
• Est. primary completion date: January 23, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Esophageal Cancer
• Esophageal Neoplasms
• Esophageal Squamous Cell Carcinoma

Intervention

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

Locations

Country	Name	City	State
China	Hangzhou Cancer Hospital	Hangzhou	Zhejiang

Sponsors (2)

Lead Sponsor	Collaborator
Hangzhou Cancer Hospital	Anhui Kedgene Biotechnology Co.,Ltd

Country where clinical trial is conducted

China, 

References & Publications (3)

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. — View 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. Review. — View 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. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Progression free survival (PFS)	From date of randomization until the date of first documented progression or date of death from any cause	1 year
Other	Overall Survival (OS)	The time from randomization to death from any cause	1 year
Other	Peripheral blood T lymphocyte subsets	Sera were collected at baseline and after the first cycle to measure T lymphocyte subsets with flow cytometry	6 weeks
Other	Tumor-infiltrating T cells	Baseline and post-treatment tissue samples were tested for the tumor-infiltrating T cells with immunofluorescence.	Baseline and after treatment
Primary	Response Rate	Response will be evaluated according to RECIST v1.1	1-3 months
Secondary	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	6 months