A Clinical Study of Anti-MUC1 CAR T Cells and PD-1 Knockout Engineered T Cells for Patients With Advanced Non-small Cell Lung Cancer
Overview
- Phase
- Phase 1
- Intervention
- CAR-T Cells
- Conditions
- Lung Neoplasm Malignant
- Sponsor
- The First Affiliated Hospital of Guangdong Pharmaceutical University
- Enrollment
- 60
- Locations
- 2
- Primary Endpoint
- Number of participants with adverse events and dose limiting toxicities as assessed by CTCAE v4.0
- Last Updated
- 7 years ago
Overview
Brief Summary
The study is to assess the safety and efficacy of the anti-MUC1 CAR T cells and /or PD-1 knockout engineered T cells for patients with advanced non-small cell lung cancer.
Detailed Description
This is a combined phase 1 and 2 clinical study. The study is to assess the safety and efficacy of the anti-MUC1 CAR T cells and /or PD-1 knockout engineered T cells for patients with advanced non-small cell lung cancer. The treatment outcomes will be compared.
Investigators
Size Chen
Professor
The First Affiliated Hospital of Guangdong Pharmaceutical University
Eligibility Criteria
Inclusion Criteria
- •MUC1 is 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
- •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 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.
Arms & Interventions
CAR-T
Anti-MUC1 CAR-T cells will be prepared ex vivo and infused back to the patients.
Intervention: CAR-T Cells
CAR-T combining PD-1 knockout
Anti-MUC1 CAR-T cells and PD-1 knockout Engineered T cells will be prepared ex vivo and infused back to the patients.
Intervention: CAR-T Cells
CAR-T combining PD-1 knockout
Anti-MUC1 CAR-T cells and PD-1 knockout Engineered T cells will be prepared ex vivo and infused back to the patients.
Intervention: CAR-T combining PD-1 Knockout
CAR-T combining PD-1 knockout
Anti-MUC1 CAR-T cells and PD-1 knockout Engineered T cells will be prepared ex vivo and infused back to the patients.
Intervention: PD-1 knockout
PD-1 knockout
PD-1 knockout Engineered T cells will be prepared ex vivo and infused back to the patients.
Intervention: PD-1 knockout
PD-1 mAb
Patients will be treated with a FDA approved monoclonal antibody for an identical course of treatment. This group will serve as PD-1 antibody treated group.
Intervention: PD-1 mAb
Sham Control
Patient's T cells will be separate without genetic or engineered modification ex vivo and infused back to the patients.
Intervention: Sham control
Outcomes
Primary Outcomes
Number of participants with adverse events and dose limiting toxicities as assessed by CTCAE v4.0
Time Frame: approximately 6 months
Safety and tolerability of dose of CART-cells and PD-1 Knockout T cells will be assessed using CTCAE v4.0.
Secondary Outcomes
- Overall Survival - OS(Up to 24 months)
- Median CAR-T cell persistence(4 years)
- Response Rate(6 months)
- Progression free survival - PFS(Up to 12 months)