PD-1 Knockout Engineered T Cells for Advanced Esophageal Cancer

• ClinicalTrials.gov Identifier: NCT03081715
• Recruitment Status: Completed
• First Posted: March 16, 2017
• Last Update Posted: June 12, 2019
• Sponsor: Hangzhou Cancer Hospital
• Collaborator: Anhui Kedgene Biotechnology Co.,Ltd
• Information provided by (Responsible Party): Shixiu Wu, Hangzhou Cancer Hospital

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.

Condition or disease	Intervention/treatment	Phase
Esophageal Cancer	Other: PD-1 Knockout T Cells	Not Applicable

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 16 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Masking Description: open-label
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: March 14, 2017
• Actual Primary Completion Date: January 23, 2018
• Actual Study Completion Date: February 28, 2018

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Response Rate [ Time Frame: 1-3 months ]
   Response will be evaluated according to RECIST v1.1

Secondary Outcome Measures :

1. 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

Other Outcome Measures:

1. 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
2. Overall Survival (OS) [ Time Frame: 1 year ]
   The time from randomization to death from any cause
3. 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
4. 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.

Eligibility Criteria

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

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

Contacts and Locations

Locations

China, Zhejiang

Hangzhou Cancer Hospital

Hangzhou, Zhejiang, China, 310002

Sponsors and Collaborators

Hangzhou Cancer Hospital

Anhui Kedgene Biotechnology Co.,Ltd

Investigators

• Principal Investigator: shixiu wu, Professor; Hangzhou Cancer Hospital

More Information

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.

• Responsible Party: Shixiu Wu, Professor, Hangzhou Cancer Hospital
• ClinicalTrials.gov Identifier: NCT03081715
• Other Study ID Numbers: HangzhouCH07
• First Posted: March 16, 2017
• Last Update Posted: June 12, 2019
• Last Verified: June 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

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

Keywords provided by Shixiu Wu, Hangzhou Cancer Hospital:

esophageal cancer; immune checkpoint; PD-1; CRISPER; autologous cell infusion

Additional relevant MeSH terms:

Esophageal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases