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Immunotherapy Using Tumor Infiltrating Lymphocytes for Patients With Advanced Liver Cancer

Primary Purpose

Liver Cancer

Status
Recruiting
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
Autologous Tumor Infiltrating Lymphocytes
Sponsored by
Zhiyong Huang
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Liver Cancer

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: 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 Criteria: 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.

Sites / Locations

  • Tongji HospitalRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (autologous tumor infiltrating lymphocytes)

Arm Description

Post-NMA lymphodepletion, patients are infused with their autologous TIL followed by IL-2 administration.

Outcomes

Primary Outcome Measures

Types and incidence of Dose-limiting toxicity (DLT) [Safety and Tolerability]
Dose-limiting toxicity (DLT) will be collected and graded according to CTCAE v5.0
Types and incidence of adverse events (AEs) ,serious adverse events (SAEs) [Safety and Tolerability]
AE will be collected and graded according to CTCAE v5.0
Maximum tolerated dose [Safety and Tolerability]
Evaluate the maximum tolerated dose of TILs in patients with advanced liver cancer

Secondary Outcome Measures

Progression-free Survival (PFS)
PFS will be calculated as the time from TIL infusion to disease progression or death from any cause (whichever occurs first) (RECIST v1.1).
Disease Control Rate (DCR)
DCR will be calculated as the percentage of patients who achieved Stable Disease(SD) or better for more than 8 weeks (RECIST v1.1).
Objective response rate (ORR)
ORR will be calculated as the percentage of patients who achieved partial response (PR) or better (RECIST v1.1).
Overall Survival (OS)
Time from TIL infusion to time of death due to any cause

Full Information

First Posted
October 3, 2023
Last Updated
October 9, 2023
Sponsor
Zhiyong Huang
Collaborators
Wuhan Elongevity Technology Co., Ltd.
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1. Study Identification

Unique Protocol Identification Number
NCT06084299
Brief Title
Immunotherapy Using Tumor Infiltrating Lymphocytes for Patients With Advanced Liver Cancer
Official Title
Immunotherapy Using Tumor Infiltrating Lymphocytes for Patients With Advanced Liver Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
May 27, 2020 (Actual)
Primary Completion Date
August 30, 2026 (Anticipated)
Study Completion Date
August 30, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Zhiyong Huang
Collaborators
Wuhan Elongevity Technology Co., Ltd.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief 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.
Detailed Description
This is an adoptive cell transfer therapy that utilizes an autologous TIL manufacturing process for the treatment of patients with advanced liver cancer. The cell transfer therapy used in this study involves patients receiving a non-myeloablative lymphodepletion preparative regimen, followed by i.v. infusion of autologous tumor-infiltrating lymphocytes followed by the administration of a regimen of IL-2.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Liver Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
16 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Treatment (autologous tumor infiltrating lymphocytes)
Arm Type
Experimental
Arm Description
Post-NMA lymphodepletion, patients are infused with their autologous TIL followed by IL-2 administration.
Intervention Type
Biological
Intervention Name(s)
Autologous Tumor Infiltrating Lymphocytes
Intervention Description
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.
Primary Outcome Measure Information:
Title
Types and incidence of Dose-limiting toxicity (DLT) [Safety and Tolerability]
Description
Dose-limiting toxicity (DLT) will be collected and graded according to CTCAE v5.0
Time Frame
1 month
Title
Types and incidence of adverse events (AEs) ,serious adverse events (SAEs) [Safety and Tolerability]
Description
AE will be collected and graded according to CTCAE v5.0
Time Frame
Up to 24 months
Title
Maximum tolerated dose [Safety and Tolerability]
Description
Evaluate the maximum tolerated dose of TILs in patients with advanced liver cancer
Time Frame
1 month
Secondary Outcome Measure Information:
Title
Progression-free Survival (PFS)
Description
PFS will be calculated as the time from TIL infusion to disease progression or death from any cause (whichever occurs first) (RECIST v1.1).
Time Frame
6 months
Title
Disease Control Rate (DCR)
Description
DCR will be calculated as the percentage of patients who achieved Stable Disease(SD) or better for more than 8 weeks (RECIST v1.1).
Time Frame
Up to 24 months
Title
Objective response rate (ORR)
Description
ORR will be calculated as the percentage of patients who achieved partial response (PR) or better (RECIST v1.1).
Time Frame
Up to 24 months
Title
Overall Survival (OS)
Description
Time from TIL infusion to time of death due to any cause
Time Frame
Up to 24 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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 Criteria: 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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Tong Yuan
Phone
86-15071338542
Email
Zyhuang126@126.com
First Name & Middle Initial & Last Name or Official Title & Degree
Tian Xia
Email
tianxia@hust.edu.cn
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Zhiyong Huang
Organizational Affiliation
Tongji Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Tongji Hospital
City
Wuhan
ZIP/Postal Code
430000
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Tong Yuan
Phone
86-15071338542
Email
Zyhuang126@126.com
First Name & Middle Initial & Last Name & Degree
Tian Xia
Email
tianxia@hust.edu.cn

12. IPD Sharing Statement

Plan to Share IPD
No

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Immunotherapy Using Tumor Infiltrating Lymphocytes for Patients With Advanced Liver Cancer

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