Clinical trial NCT03356808: Antigen-specific T Cells Against Lung Cancer
Official title: Multicenter Trial of Cancer Antigen-specific T Cells in the Treatment of Lung Cancer
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Lung Cancer
Keywords: Lung cancer
CAR-T
mesothelin
Muc1
GD2
MAGE-A4
Lead sponsor: Shenzhen Geno-Immune Medical Institute
Sponsor class: OTHER
First posted: 2017-11-29
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Safety of engineered T cells in patients using CTCAE version 4.0 standard to evaluate the level of adverse events
timeFrame: 3 months
Secondary outcomes:
measure: Persistence and proliferation of engineered antigen-specific T cells in patients
timeFrame: 3 months
measure: Anti-tumor effects
timeFrame: 1 year
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Jinshazhou Hospital of Guangzhou University of Chinese Medicine
state: Guangdong
city: Shenzhen
country: China
facility: Shenzhen Geno-immune Medical Institute
state: Guangdong
city: Kunming
country: China
facility: Yunnan Cancer Hospital & The Third Affiliated Hospital of Kunming Medical University & Yunnan Cancer Center
state: Yunnan
Study officials:
affiliation: Shenzhen Geno-Immune Medical Institute
name: Lung-Ji Chang, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Jinshazhou Hospital of Guangzhou University of Chinese Medicine
name: Qichun Cai, MD
role: STUDY_DIRECTOR
affiliation: Yunnan Cancer Hospital & The Third Affiliated Hospital of Kunming Medical University & Yunnan Cancer Center
name: Xun Lai, MD
role: STUDY_DIRECTOR
References: