Antigen-specific T Cells Against Lung Cancer

NCT ID: NCT03356808

Last Updated: 2019-09-19

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-12-15
• Study Completion Date: 2020-12-31

Brief Summary

The purpose of this clinical trial is to assess the feasibility, safety and efficacy of cancer antigen-specific T cells targeting lung cancer. The cancer targeting antigens are identified through immunostaining of patient's cancer specimens. Another goal of the study is to learn more about the persistence and function of the ex vivo manipulated antigen-specific T cells in the body.

Detailed Description

Lung cancer is a malignancy characterized by uncontrolled cell growth in tissues of the lung. There are two main types of lung cancer, small-cell lung carcinoma (SCLC) and non-small-cell lung carcinoma (NSCLC). In 2012, lung cancer occurred in 1.8 million people and resulted in 1.6 million deaths worldwide. Common treatments include surgery, chemotherapy, and radiotherapy, but in relapsed cancer patients, such treatments often have limited successes.

In this study, the participant's peripheral blood mononuclear cells will be collected for antigen-specific T cell preparation, and/or modified using an advanced lentiviral vector system. Then the antigen-specific T cells, called engineered immune effectors (EIEs) or chimeric antigen receptor modified-T cells (CAR T), which can recognize specific molecules that are expressed by the lung cancer cells, are given back to the participant by intravenous infusion.

The purpose of this clinical trial is to assess the feasibility, safety and efficacy of T cell immunotherapy targeting single or multiple cancer antigens. The lung cancer antigens include known tumor antigens such as MAGE-A1, MAGE-A4, MucI, GD2, and mesothelin, as well as novel cancer antigens. Another goal of the study is to learn more about the persistence and function of the specific CAR T cells in the body.

Conditions

Lung Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Lung cancer-specific T cells

Peripheral blood mononuclear cells (PBMCs) of patients, who have cancer antigen identified lung cancer, will be obtained through apheresis, and T cells will be activated and ex vivo engineered.

Group Type: EXPERIMENTAL

Lung cancer-specific T cells

Intervention Type: BIOLOGICAL

1 infusion, for 1x10\^6\~1x10\^7 cells/kg via IV

Interventions

Lung cancer-specific T cells

1 infusion, for 1x10\^6\~1x10\^7 cells/kg via IV

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

1. Patients with stage III, IV or relapsed lung cancer confirmed by histology and biopsy.

2. Age: ≥ 18 years and ≤ 80 years.

3. 4 weeks at least since last chemotherapy or radiotherapy and 2 weeks at least since last systemic steroid hormone and other immunosuppressive therapy.

4. Side Effects of Chemotherapy have subsided.

5. Cancer specific antigens are identified and shown to express at high levels (>2+) in malignant tissues by immuno-histochemical staining or flow cytometry.

6. Karnofsky/Lansky ≥ 50%.

7. Expected survival ≥ 6 weeks.

Initial hematopoietic conditions with

• neutrophils (ANC) ≥ 1×10^6/L;
• platelet (PLT) ≥ 1×10^8/L.

Proper renal and hepatic functions (ULN denotes "upper limit of normal range") with

• serum creatinine ≤ 2×ULN;
• serum bilirubin ≤ 3×ULN;
• AST/ALT ≤ 5×ULN.

10. Oxygen saturation ≥ 90%. 11. Written, informed consent obtained prior to any study-specific procedures.

Exclusion Criteria

1. Airway obstruction caused by tumor.

2. History of epilepsy or other central nervous system diseases.

3. Patients who require systemic corticosteroid or other immunosuppressive therapy.

4. History of prolonged or serious heart disease during QT.

5. history of serious cyclophosphamide toxicity.

6. Current or recent treatment (within the 28-day period prior to Day 0) with another investigational drug or previous participation in any immune cell therapy study.

Inadequate liver and renal function with

• serum creatinine > 2.5 mg/dl;
• serum (total) bilirubin > 2.0 mg/dl;
• AST & ALT > 3 x ULN.

8. Pregnant or lactating females. 9. Serious active infection during screening. 10. Active HIV, Hepatitis B virus (HBV), Hepatitis C virus (HCV) infection or uncontrolled infection.

11. Patients, in the opinion of investigators, may not be eligible or not able to comply with the study.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Shenzhen Geno-Immune Medical Institute

OTHER

Sponsor Role: lead

Responsible Party

Lung-Ji Chang

President

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Lung-Ji Chang, PhD

Role: PRINCIPAL_INVESTIGATOR

Shenzhen Geno-Immune Medical Institute

Qichun Cai, MD

Role: STUDY_DIRECTOR

Jinshazhou Hospital of Guangzhou University of Chinese Medicine

Xun Lai, MD

Role: STUDY_DIRECTOR

Yunnan Cancer Hospital & The Third Affiliated Hospital of Kunming Medical University & Yunnan Cancer Center

Locations

Jinshazhou Hospital of Guangzhou University of Chinese Medicine

Guangzhou, Guangdong, China

Site Status: RECRUITING

Shenzhen Geno-immune Medical Institute

Shenzhen, Guangdong, China

Site Status: RECRUITING

Yunnan Cancer Hospital & The Third Affiliated Hospital of Kunming Medical University & Yunnan Cancer Center

Kunming, Yunnan, China

Site Status: RECRUITING

Countries

China

Central Contacts

Lung-Ji Chang, PhD

Role: CONTACT

c@szgimi.org

86-075586725195

Facility Contacts

Qichun Cai, MD

Role: primary

86-13802830754

Lung-Ji Chang, PhD

Role: primary

c@szgimi.org

86-075586725195

Xun Lai, MD

Role: primary

1729112214@qq.com

13577096609

Other Identifiers

GIMI-IRB-17023

Identifier Type: -

Identifier Source: org_study_id