PD-1 Knockout Engineered T Cells for Advanced Esophageal Cancer

Study Overview
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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.

Official Title
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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

Conditions
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Esophageal Cancer

Intervention / Treatment
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* Other: PD-1 Knockout T Cells


Participation Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental Group<br>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<br>* Programmed cell death 1(PD-1) gene will be knocked out by CRISPR Cas9<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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esophageal cancer, immune checkpoint, PD-1, CRISPER, autologous cell infusion