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

Primary Purpose

Advanced Esophageal Cancer

Status

Unknown status

Phase

Phase 1

Locations

China

Study Type

Interventional

Intervention

Anti-MUC1 CAR-T cells

PD-1 knockout Engineered T cells

CAR-T combined with PD-1 Knockout T cells

About this trial

This is an interventional treatment trial for Advanced Esophageal Cancer focused on measuring Esophageal cancer, Neoplasms, Esophageal, Cancer of Esophagus, Solid tumor

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

First Affiliated Hospital of Guangdong Pharmaceutical UniversityRecruiting
Professor Size ChenRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Arm Label

Treatment with Anti-MUC1 CAR-T cells

Combination Therapy: CAR-T combining PD-1 knockout T Cells

Treatment with PD-1 knockout Engineered T cells

Arm Description

Anti-MUC1 CAR-T cells will be prepared ex vivo using the T cells from the patients and infused back to the patients.

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.

PD-1 knockout Engineered T cells will be prepared ex vivo using the T cells from the patients and infused back to the patients.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Response Rate

Will be assessed according to the revised RECIST guideline v1.1

Overall Survival - OS

Measure the time from enrollment to death

Progression free survival - PFS

Time from enrollment to date of first documented progression or date of death.

Median CAR-T cell persistence

Will be measured by quantitative RT-PCR

Full Information

NCT ID

NCT03706326

First Posted

October 11, 2018

Last Updated

October 11, 2018

Sponsor

The First Affiliated Hospital of Guangdong Pharmaceutical University

Collaborators

Guangzhou Anjie Biomedical Technology Co., Ltd.

1. Study Identification

Unique Protocol Identification Number

NCT03706326

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

October 2018

Overall Recruitment Status

Unknown status

Study Start Date

September 28, 2018 (Actual)

Primary Completion Date

September 28, 2021 (Anticipated)

Study Completion Date

September 28, 2021 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

The First Affiliated Hospital of Guangdong Pharmaceutical University

Collaborators

Guangzhou Anjie Biomedical Technology Co., Ltd.

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief Summary

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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Advanced Esophageal Cancer

Keywords

Esophageal cancer, Neoplasms, Esophageal, Cancer of Esophagus, Solid tumor

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Parallel Assignment

Masking

Participant

Allocation

Randomized

Enrollment

20 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Treatment with Anti-MUC1 CAR-T cells

Arm Type

Experimental

Arm Description

Anti-MUC1 CAR-T cells will be prepared ex vivo using the T cells from the patients and infused back to the patients.

Arm Title

Combination Therapy: CAR-T combining PD-1 knockout T Cells

Arm Type

Experimental

Arm Description

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.

Arm Title

Treatment with PD-1 knockout Engineered T cells

Arm Type

Experimental

Arm Description

PD-1 knockout Engineered T cells will be prepared ex vivo using the T cells from the patients and infused back to the patients.

Intervention Type

Biological

Intervention Name(s)

Anti-MUC1 CAR-T cells

Intervention Description

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.

Intervention Type

Biological

Intervention Name(s)

PD-1 knockout Engineered T cells

Intervention Description

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.

Intervention Type

Combination Product

Intervention Name(s)

CAR-T combined with PD-1 Knockout T cells

Intervention Description

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

Primary Outcome Measure Information:

Title

Number of participants with adverse events and dose limiting toxicities as assessed by CTCAE v4.0

Description

Safety and tolerability of dose of CART-cells and PD-1 Knockout T cells will be assessed using CTCAE v4.0.

Time Frame

approximately 12 months

Secondary Outcome Measure Information:

Title

Response Rate

Description

Will be assessed according to the revised RECIST guideline v1.1

Time Frame

12 months

Title

Overall Survival - OS

Description

Measure the time from enrollment to death

Time Frame

Up to 24 months

Title

Progression free survival - PFS

Description

Time from enrollment to date of first documented progression or date of death.

Time Frame

Up to 12 months

Title

Median CAR-T cell persistence

Description

Will be measured by quantitative RT-PCR

Time Frame

3 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

80 Years

Accepts Healthy Volunteers

Eligibility Criteria

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.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Size Chen, MD, PhD

Phone

+8613720956393

13720956393@139.com

First Name & Middle Initial & Last Name or Official Title & Degree

Zhizhou Huang, MSc

Phone

+8613268258980

hzhizhou@sina.com

Facility Information:

Facility Name

First Affiliated Hospital of Guangdong Pharmaceutical University

City

Guangzhou

State/Province

Guangdong

ZIP/Postal Code

510080

Country

China

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Guobiao Huang

Phone

86-20-39352064

153706227@qq.com

Facility Name

Professor Size Chen

City

Guangzhou

State/Province

Guangdong

ZIP/Postal Code

510080

Country

China

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Size Chen, MD,PhD

Phone

+8613720956393

13720956393@139.com

First Name & Middle Initial & Last Name & Degree

Zhizhou Huang, MSc

Phone

+8613268258980

hzhizhou@sina.com

First Name & Middle Initial & Last Name & Degree

Yiguang Lin, MD, PhD

First Name & Middle Initial & Last Name & Degree

Size Chen, MD, PhD

First Name & Middle Initial & Last Name & Degree

Micheal Yin, PhD

12. IPD Sharing Statement

Learn more about this trial

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

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