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

NCT ID: NCT03706326

Last Updated: 2018-10-16

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE1/PHASE2

Total Enrollment

20 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-09-28

Study Completion Date

2021-09-28

Brief Summary

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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

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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.

Conditions

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Advanced Esophageal Cancer

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Participants

Study Groups

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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.

Group Type EXPERIMENTAL

Anti-MUC1 CAR-T cells

Intervention Type BIOLOGICAL

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.

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.

Group Type EXPERIMENTAL

CAR-T combined with PD-1 Knockout T cells

Intervention Type COMBINATION_PRODUCT

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

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.

Group Type EXPERIMENTAL

PD-1 knockout Engineered T cells

Intervention Type BIOLOGICAL

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.

Interventions

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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.

Intervention Type 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.

Intervention Type BIOLOGICAL

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

Intervention Type COMBINATION_PRODUCT

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Guangzhou Anjie Biomedical Technology Co., Ltd.

INDUSTRY

Sponsor Role collaborator

The First Affiliated Hospital of Guangdong Pharmaceutical University

OTHER

Sponsor Role lead

Responsible Party

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Size Chen

Associate Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Locations

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First Affiliated Hospital of Guangdong Pharmaceutical University

Guangzhou, Guangdong, China

Site Status RECRUITING

Professor Size Chen

Guangzhou, Guangdong, China

Site Status RECRUITING

Countries

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China

Central Contacts

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Size Chen, MD, PhD

Role: CONTACT

+8613720956393

Zhizhou Huang, MSc

Role: CONTACT

+8613268258980

Facility Contacts

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Guobiao Huang

Role: primary

86-20-39352064

Size Chen, MD,PhD

Role: primary

+8613720956393

Zhizhou Huang, MSc

Role: backup

+8613268258980

Other Identifiers

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2018-6301

Identifier Type: -

Identifier Source: org_study_id

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