RecruitingPhase 1NCT06084299

Immunotherapy Using Tumor Infiltrating Lymphocytes for Patients With Advanced Liver Cancer

Sponsor

Zhiyong Huang

Enrollment

16 participants

Start Date

May 27, 2020

Study Type

INTERVENTIONAL

Conditions

Liver Cancer

Summary

Single-arm, open-label, interventional study evaluating adoptive cell therapy (ACT) with autologous tumor-infiltrating lymphocytes (TIL) infusion followed by IL-2 after a non-myeloablative(NMA) lymphodepletion preparative regimen for the treatment of patients with advanced liver cancer.

Eligibility

Min Age: 18 YearsMax Age: 70 Years

Inclusion Criteria12

The subjects must be informed of the study before the test and voluntarily sign a written informed consent.
Age of the patients was between 18\~70 years
Eligible patients have histologically proven advanced liver cancer
Eastern Cooperative Oncology Group (ECOG) performance status was 0-1
Metastatic lesions are confirmed by PET-CT, CT, MR and/or intraoperative exploration (more than 3, at least one accessible metastasis to procure for TILs)
Patients have at least one separate additional measurable tumour lesion according to RECIST version 1.1 standard.
The disease has progressed after at least two previous lines of standard treatment and there is no effective treatment option available
Adequate normal organ and marrow function were present, including absolute neutrophil count ≥ 1×10\^9/L, leukocyte count ≥ 3×10\^9/L, platelet count ≥ 75×10\^9/L, hemoglobin ≥ 80 g/L, AST and ALT ≤ 2× of upper limit of normal, Serum creatinine ≤ 1.5× upper normal limits, Serum total bilirubin ≤ 1.5× upper normal limits
Female subjects of childbearing age must have a negative urine or serum HCG test within 7 days before cell reinfusion
Provide at least one gram of fresh tumor tissue and 10ml of peripheral blood for whole exome sequencing and TIL isolation and culture.
Expected survival was at least 3 months
Child-Push liver function score grade is A within seven days before the cell reinfusion.

Exclusion Criteria22

With previous or concurrent other active cancer (except carcinoma in situ that has been cured without onset within 5 years, or those that can be cured by adequate treatment)
Patients with metastasis to Central Nervous System or brain
Have received organ transplantation in the past
Received major liver surgery within 4 weeks before the first administration (except liver metastases biopsy).
Received local treatment of the liver or other parts within 4 weeks before the first administration (transcatheter arterial chemoembolization \[TACE\], transcatheter arterial embolization \[TAE\], hepatic artery infusion \[HAI\], radiotherapy, radioembolization or ablation). Subjects are not eligible to participate in the study if the above-mentioned treatment is carried out between the last dose of sorafenib or oxaliplatin-containing regimen and the first study administration.
After CT angiography examination, there is severe arterial embolism or hepatic artery vascular variation.
APTT or PT \>= 5 UNL, or with bleeding evidence in two months or bleeding history in prior to the clinical study, no matter how serious it is
Active inflammation within 7 days after systemic antibiotics treatment
Subjects who have undergone major surgery or severe trauma such as laparotomy, thoracotomy, and laparoscopic organ removal within 4 weeks before enrollment.
Active coronary artery disease, serious or unstable angina pectoris, or newly diagnosed angina pectoris or myocardial infarction within 12 months prior to the clinical study
Thrombosis or embolism event within 12 months prior to the clinical study, such as cerebrovascular accident ( including TIA) or pulmonary embolism
Congestive heart failure of NYHA \>= Class II
Human immunodeficiency virus (HIV) infection or known acquired immunodeficiency syndrome (AIDS), untreated active hepatitis (hepatitis B, defined as HBV-DNA ≥ 500 IU/ml C Hepatitis, defined as HCV-RNA higher than the detection limit of the analytical method) or co-infection with hepatitis B and hepatitis C.
Presence of any active, known or suspected autoimmune disease. Subjects in a stable state who do not require systemic immunosuppressive therapy are allowed, such as: type 1 diabetes mellitus, hypothyroidism requiring only hormone replacement therapy, and skin diseases that do not require systemic therapy (e.g., vitiligo, psoriasis disease and hair loss).
Any interstitial lung disease, noninfectious causes of lung inflammation, or uncontrolled systemic disease (e.g. diabetes, pulmonary fibrosis, or acute pneumonia)
Any adverse event of CTCAE (Ver 5.0) grade 2 or higher induced by previous treatment, except anemia, hair loss, and skin pigmentation
Pregnant or lactating women or those who are positive in pregnancy test before 1st injection
The investigator believes that the subject has any clinical or laboratory abnormalities or compliance problems and is not suitable for participating in this clinical study.
With serious psychological or mental abnormalities
Joined other clinical trials in four weeks prior to this study
Patients who have a history of hypersensitivity to cyclophosphamide and fludarabine.
Other researchers think that they are not suitable for enrollment.

Interventions

BIOLOGICALAutologous Tumor Infiltrating Lymphocytes

Fresh tumor samples will be resected from enrolled patients. Autologous TILs will be extracted and reinfused to corresponding patients after ex vivo stimulation, activation, and extensive expansion.

Locations(1)

Tongji Hospital

Wuhan, China

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NCT06084299

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