PD-1 Knockout Engineered T Cells for Advanced Esophageal Cancer

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

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.

Study Overview

• Status: Completed
• Conditions: Esophageal Cancer
• Intervention / Treatment: Other: PD-1 Knockout T Cells

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: Interventional
• Enrollment (Actual): 16
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310002
      • Hangzhou Cancer Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

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.

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response Rate	Response will be evaluated according to RECIST v1.1	1-3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression free survival (PFS)	From date of randomization until the date of first documented progression or date of death from any cause	1 year
Overall Survival (OS)	The time from randomization to death from any cause	1 year
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
Tumor-infiltrating T cells	Baseline and post-treatment tissue samples were tested for the tumor-infiltrating T cells with immunofluorescence.	Baseline and after treatment

Collaborators and Investigators

• Sponsor: Hangzhou Cancer Hospital
• Collaborators: Anhui Kedgene Biotechnology Co.,Ltd
• Investigators: Principal Investigator: shixiu wu, Professor, Hangzhou Cancer Hospital

Publications and helpful links

General Publications

• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): March 14, 2017
• Primary Completion (Actual): January 23, 2018
• Study Completion (Actual): February 28, 2018

Study Registration Dates

• First Submitted: March 11, 2017
• First Submitted That Met QC Criteria: March 11, 2017
• First Posted (Actual): March 16, 2017

Study Record Updates

• Last Update Posted (Actual): June 12, 2019
• Last Update Submitted That Met QC Criteria: June 10, 2019
• Last Verified: June 1, 2019

More Information

Terms related to this study

• Keywords: esophageal cancer; PD-1; immune checkpoint; CRISPER; autologous cell infusion
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Head and Neck Neoplasms; Esophageal Diseases; Esophageal Neoplasms
• Other Study ID Numbers: HangzhouCH07

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No