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

The First Affiliated Hospital of Guangdong Pharmaceutical University

Status and phase: Unknown; Phase 2; Phase 1

Conditions: Advanced Esophageal Cancer

Treatments: Biological: PD-1 knockout Engineered T cells; Biological: Anti-MUC1 CAR-T cells; Combination Product: CAR-T combined with PD-1 Knockout T cells

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT03706326

2018-6301

Details and patient eligibility

About

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.

Full 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.

Enrollment: 20 estimated patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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20 participants in 3 patient groups

Treatment with Anti-MUC1 CAR-T cells

Experimental group

Description:

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

Treatment:

Biological: Anti-MUC1 CAR-T cells

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

Experimental group

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.

Treatment:

Combination Product: CAR-T combined with PD-1 Knockout T cells

Treatment with PD-1 knockout Engineered T cells

Experimental group

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.

Treatment:

Biological: PD-1 knockout Engineered T cells