Clinical Safety and Preliminary Efficacy of MAGE-A4 TCR Gene-Modified T Cells to Treat Malignant Tumors

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the clinical safety and preliminary efficacy of MAGE-A4 TCR Gene-Modified T lymphocytes in the treatment of malignant solid tumor patients, such as malignant melanoma and lung cancer.

Official Title
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Phase 1 Study of MAGE-A4 TCR Gene-Modified T Cells to Treat Malignant Tumors

Conditions
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Malignant Solid Tumors

Intervention / Treatment
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* Biological: MAGE-A4 TCR Gene-Modified T Cells


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Sex: male or female Age: from 18 to 80 years Patients must have histologically confirmed solid tumors that have failed standard therapies (surgery, chemotherapy, radiotherapy) and for which no curative options exist, including, but not limited to: Non-Small Cell Lung Carcinoma Malignant melanoma Esophageal carcinoma Head and neck carcinoma HLA-A*24:02 MAGE-A4 positive in the test by RT-PCR on tumor tissue or immunohistochemistry of resected tissue of the patient. PS ECOG 0 or <2 Laboratory tests results 7 days before the start of treatment: White blood cells: more than 3.0 × 109/L Platelets: more than 100 × 109/L Neutrophils: more than 1.5 × 109/L Hemoglobin: more than 80g/L Serum glutamate pyruvate transaminase: less than 2.5 folds of the upper normal limit (ULN) Serum glutamic-oxal (o) acetic transaminase: less than 2.5 × ULN Serum bilirubin: less than 1.25 × ULN Serum creatinine: less than 1.25 × ULN Pregnancy test: the test of women of child-bearing period must be negative 7 days before the start of treatment Contraception: male and female subjects of child-bearing period must adopt a reliable method of contraception before entry into this study until 30 days after stopping this study Informed consent: subject must have the ability to understand and voluntarily sign a written informed consent Exclusion Criteria: Patients with life-threatening condition or complication other than their basic disease Pregnant or lactation. Patients both males and female with reproductive potential (i.e. menopausal for less than 1 year and not surgically sterilized) must practice effective contraceptive measures throughout the study. Women of childbearing potential must provide a negative pregnancy test (serum or urine) within 14 days prior to registration Active systemic infections History of neoplasms: other neoplasms Medical history: active CNS disease, or congestive heart failure, or severe coronary artery disease, or cardiac arrhythmias, or concomitant corticosteroid therapy Metastasis: clinical symptoms of brain metastasis Other clinical trial: the subject received other clinical trial before this study Laboratory tests: the serum test of human immunodeficiency virus, or hepatitis B virus, or hepatitis C virus was positive Compliance: poor compliance

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MAGE-A4 TCR Gene-Modified T Cells<br> | Biological: MAGE-A4 TCR Gene-Modified T Cells<br>* The study consists of a 2-dose escalation scheme, and the patient receives twice in each dose. The starting dose is 1-3 x 10^9 cells of each TCR gene-modified cells and the second one is 3-8 x 10^9 cells of each TCR gene-modified cells. Two weeks after the first infusion the patient receives the same dose again, followed by infusions of IL-2 for 5 days. Thereafter, the patient receives peptide vaccinations on days 21 and 28.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate | CR + PR = ORR | Up to 12 months |