CAR T and PD-1 Knockout Engineered T Cells for Esophageal Cancer

Combination Therapy of Anti-MUC1 CAR T Cells and PD-1 Knockout Engineered T Cells for Advanced Esophageal Cancer

The study is to assess the safety and efficacy of the immunotherapies using anti-MUC1 CAR T cells and /or PD-1 knockout engineered T cells in the treatment of patients with advanced esophageal cancer.

Study Overview

• Status: Unknown
• Conditions: Advanced Esophageal Cancer
• Intervention / Treatment: Biological: Anti-MUC1 CAR-T cells; Combination product: CAR-T combined with PD-1 Knockout T cells; Biological: PD-1 knockout Engineered T cells

Detailed Description

This is a combined phase 1 and 2 clinical study. The aim of the study is to assess the safety and efficacy of the immunotherapies using anti- MUC1 CAR T cells alone, anti- MUC1 CAR T combining PD-1 knockout engineered T cells, and PD-1 knockout engineered T cell only in the treatment of patients with advanced esophageal cancer. The treatment outcomes from each group will be compared.

• Study Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510080
      • Recruiting
      • First Affiliated Hospital of Guangdong Pharmaceutical University
      • Contact: Guobiao Huang; Phone Number: 86-20-39352064; Email: 153706227@qq.com
    • Guangzhou, Guangdong, China, 510080
      • Recruiting
      • Professor Size Chen
      • Contact: Zhizhou Huang, MSc; Phone Number: +8613268258980; Email: hzhizhou@sina.com
      • Contact: Size Chen, MD,PhD; Phone Number: +8613720956393; Email: 13720956393@139.com
      • Principal Investigator: Yiguang Lin, MD, PhD
      • Principal Investigator: Size Chen, MD, PhD
      • Sub-Investigator: Micheal Yin, PhD

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:

• Confirmed diagnosis of advanced esophageal cancer (phase IIIb-IV) according to NCCN clinical practice guidelines in Oncology:Esophageal and Esophagogastric Junction Cancers (2018.V1).
• MUC1 is highly expressed in malignancy tissues by immuno-histochemical (IHC).
• Eastern cooperative oncology group (ECOG) performance status of 0-1 or karnofsky performance status (KPS) score is higher than 60.
• Patients have a life expectancy > 12 weeks.
• Adequate venous access for apheresis or venous sampling, and no other contraindications for leukapheresis.
• Negative pregnancy test for females of child-bearing potentials.
• Adequate bone marrow, liver and renal function as assessed by the following laboratory requirements: White blood cell count (WBC) ≥ 2500c/ml, Platelets ≥ 50×10^9/L, Hb ≥ 9.0g/dL, lymphocyte (LY) ≥ 0.7×10^9/L, LY% ≥ 15%, Alb ≥ 2.8g/dL, serum lipase and amylase < 1.5×upper limit of normal, serum creatinine ≤ 2.5mg/dL, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 5×upper limit of normal, serum total bilirubin ≤ 2.0mg/dL. These tests must be conducted within 7 days prior to registration.
• Signed informed consent form.

Exclusion Criteria:

• Number of T cells is less than 10% or the amplification of the T cells via artificial antigen presenting cell (aAPC) stimulation is less than 5 times.
• Patients with symptomatic central nervous system (CNS) involvement.
• Pregnant or nursing women.
• Known HIV, HBV and HCV infection.
• Serious illness or medical condition which would not permit the patient to be managed according to the protocol, including active uncontrolled infection, major cardiovascular, coagulation disorders, respiratory or immune system, myocardial infarction, cardiac arrhythmias, obstructive/restrictive pulmonary disease, or psychiatric or emotional disorders.
• History of severe immediate hypersensitivity to any of the agents including cyclophosphamide, fludarabine, or aldesleukin.
• Concurrent use of systemic steroids. Recent or current use of inhaled steroids is not exclusionary.
• Previously treatment with any gene therapy products.
• The existence of unstable or active ulcers or gastrointestinal bleeding. Patients with portal vein vascular invasion or extrahepatic, are excluded from this study.
• Patients with a history of organ transplantation or are waiting for organ transplantation.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment with Anti-MUC1 CAR-T cells; Anti-MUC1 CAR-T cells will be prepared ex vivo using the T cells from the patients and infused back to the patients.	Biological: Anti-MUC1 CAR-T cells; Using the T cells from the patients' blood to produce anti-MUC1 CAR-T Cells and then the cells will be infused back to the patients.
Experimental: Combination Therapy: CAR-T combining PD-1 knockout T Cells; Anti-MUC1 CAR-T cells and PD-1 knockout Engineered T cells will be prepared ex vivo using the T cells from the patients and infused back to the patients.	Combination product: CAR-T combined with PD-1 Knockout T cells; Using the T cells from the blood of the patients to prepare anti-MUC1 CAR-T Cells and PD-1 knockout T cells, then the cells will be infused back to the patients
Experimental: Treatment with PD-1 knockout Engineered T cells; PD-1 knockout Engineered T cells will be prepared ex vivo using the T cells from the patients and infused back to the patients.	Biological: PD-1 knockout Engineered T cells; Using the T cells from the blood of the patients to prepare PD-1 knockout T cells, then the cells will be infused back to the patients.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with adverse events and dose limiting toxicities as assessed by CTCAE v4.0	Safety and tolerability of dose of CART-cells and PD-1 Knockout T cells will be assessed using CTCAE v4.0.	approximately 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response Rate	Will be assessed according to the revised RECIST guideline v1.1	12 months
Overall Survival - OS	Measure the time from enrollment to death	Up to 24 months
Progression free survival - PFS	Time from enrollment to date of first documented progression or date of death.	Up to 12 months
Median CAR-T cell persistence	Will be measured by quantitative RT-PCR	3 years

Collaborators and Investigators

• Sponsor: The First Affiliated Hospital of Guangdong Pharmaceutical University
• Collaborators: Guangzhou Anjie Biomedical Technology Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): September 28, 2018
• Primary Completion (Anticipated): September 28, 2021
• Study Completion (Anticipated): September 28, 2021

Study Registration Dates

• First Submitted: October 11, 2018
• First Submitted That Met QC Criteria: October 11, 2018
• First Posted (Actual): October 16, 2018

Study Record Updates

• Last Update Posted (Actual): October 16, 2018
• Last Update Submitted That Met QC Criteria: October 11, 2018
• Last Verified: October 1, 2018

More Information

Terms related to this study

• Keywords: Solid tumor; Esophageal cancer; Neoplasms, Esophageal; Cancer of Esophagus
• 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: 2018-6301

Drug and device information, study documents

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