Back to resultsStudy Of B7H3 CAR-T Cells in Treating Advanced Liver Cancer
Primary Purpose
Hepatocellular Carcinoma
Status
Recruiting
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
fhB7H3.CAR-Ts
Fludarabine
Cyclophosphamide
Sponsored by
About this trial
This is an interventional treatment trial for Hepatocellular Carcinoma focused on measuring Fully human B7H3 CAR-T, Recurrent Advanced Hepatocellular Carcinoma
Eligibility Criteria
Inclusion Criteria:
- Subjects should be 18-70 years old.
- Subject has adequate performance status as defined by ECOG score of≤ 2.
- Expected life expectancy is no less than 12 weeks.
- Subjects must have histologically or cytologically confirmed unresectable, recurrent and / or metastatic hepatocellular carcinoma (HCC). And tumor tissues are measured positive for B7H3 expression.
- Child-Pugh A, B grade.
Blood routine:
white blood cell count≥ 2.5 × 10^9 / L; hemoglobin≥ 9 g/dL; platelet count≥ 50 × 10^9 / L; lymphocyte proportion≥ 15 %;
Adequate organ function. Patients' main organs ( heart, lung, liver, kidney, etc. ) function well:
ALT and AST≤ 5 × ULN; ALB≥ 30 g/L； Total bilirubin≤ 2.5 × ULN； Serum creatinine< 220μmol/L; Indoor oxygen saturation ≥ 95 %; Left ventricular ejection fraction≥ 40%;
- No allergic reaction to contrast agents.
- Procurement and T-cell production eligibility: a previously evaluation confirmed autologous peripheral blood mononuclear cells can be used for T-cell production.
- Patients or their legal guardians voluntarily participate in and sign the informed consent form.
Exclusion Criteria:
- The subject is a pregnant or lactating woman.
- The subjects have infectious diseases (such as HIV, syphilis, active tuberculosis, etc.);
- The subject has active infection or coagulation dysfunction.
- Subjects with previous hepatic encephalopathy.
- The subject is on anticoagulation or antiplatelet therapy.
- The subject is an organ transplant or waiting for transplant.
- Subjects with mental or psychological diseases who cannot cooperate with treatment and efficacy evaluation.
- The subjects are highly allergic or have a history of severe allergies.
- The subject has received chemotherapy/radiotherapy within the past 4 weeks.
- The subject has a history of cellular immunotherapy or antibody therapy.
- The subject is receiving systemic hormone therapy.
- Subjects with systemic infection or severe local infection requiring anti-infection treatment.
- The subject has dysfunction of important organs such as heart, lung, brain, liver, and kidney.
- The subject is participating in other clinical research.
- The doctor believes that there are other reasons not to be included in the treatment.
- Unwilling or unable to provide consent/assent for participation in the study.
Sites / Locations
- The Affiliated Hospital of Xuzhou Medical UniversityRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
fhB7H3.CAR-T cells
Arm Description
In phase I study , 9 enrolled patients diagnosed with advanced liver cancer will receive one-time transhepatic arterial infusion of fhB7H3.CAR-Ts at the doses of 1×10^6/kg, 3×10^6/kg and 5×10^6/kg, 3 patients for each dose. To further confirm the therapeutic efficacy, in phase II study, 6 enrolled patients will receive an optimal dose (balancing effectiveness and toxicity) of fhB7H3.CAR-Ts.
Outcomes
Primary Outcome Measures
Safety of fhB7H3.CAR-T cells
Adverse events, including the type, frequency, severity and duration, such as cytokine release syndrome (CRS), on-target off-tumor, immune effector cell-associated neurotoxicity syndrome, will be monitored and assessed.
Objective response of fhB7H3.CAR-T cells
Objective response rate (ORR) including complete response (CR), partial response (PR), and/or stable disease, will be determined by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria.
Complete Response (CR): disappearance of all target lesions, all target nodules must be reduced to normal size (short axis <10 mm).
Partial Response (PR): >=30% decrease in the sum of the longest diameter of target lesions. Stable Disease (SD): no response or less response than Partial or Progressive.
Progressive Disease (PD): 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
Secondary Outcome Measures
In vivo persistence of fhB7H3.CAR-T cells
Presence of CAR T cells in the peripheral blood will be assessed.
Full Information
NCT ID
NCT05323201
First Posted
February 13, 2022
Last Updated
April 5, 2022
Sponsor
The Affiliated Hospital of Xuzhou Medical University
Collaborators
Xuzhou Medical University, IIT MediTech Co. Ltd
1. Study Identification
Unique Protocol Identification Number
NCT05323201
Brief Title
Study Of B7H3 CAR-T Cells in Treating Advanced Liver Cancer
Official Title
A Single-Arm, Open-Label Study to Evaluate Safety and Efficacy of B7H3 or HBsAg Targeting CAR-T in Treating Advanced Hepatocellular Carcinoma
Study Type
Interventional
2. Study Status
Record Verification Date
February 2022
Overall Recruitment Status
Recruiting
Study Start Date
February 10, 2022 (Actual)
Primary Completion Date
February 10, 2024 (Anticipated)
Study Completion Date
February 10, 2027 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
The Affiliated Hospital of Xuzhou Medical University
Collaborators
Xuzhou Medical University, IIT MediTech 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
This is single center, open-label phase I/II, non-randomized study which will enroll patients with recurrent advanced hepatocellular carcinoma to evaluate the safety, feasibility, and efficacy of fully human B7H3 CAR-T in treating hepatocellular carcinoma.
Detailed Description
Chimeric antigen-modified T cells are genetically modified T cells that use gene transduction technology to introduce CARs, containing tumor antigen-specific recognition single-chain antibodies and T cell activation motifs, into patient T cells, so that these transduction CAR-T cells can directly recognize the specific antigen on tumor cells, thereby killing tumor cells.
Previous studies have confirmed that B7H3 is highly expressed in hepatocellular carcinoma cell lines, which is negatively correlated with the ten-year survival of patients. It is suggested that B7H3 is a specific therapeutic target for liver cancer.
The purpose of this study is to test the safety and efficacy of a newly developed fully human scFv-armed B7H3 targeting chimeric antigen receptor T cells (fhB7H3.CAR-Ts), which are supposed to attack and eliminate B7H3-positive cancer cells.
The investigators designed a single-arm open-label clinical study, the participants' peripheral blood mononuclear cells will be collected and used to manufacture fhB7H3.CAR-Ts. Before infusion, the patients will receive lymphodepletion chemotherapy with cyclophosphamide and fludarabine for three consecutive days. Two days later after lymphodepletion, the fhB7H3.CAR-Ts would be given through transhepatic arterial infusion. From the day of infusion, participants' peripheral blood will be collected twice a week in the first month to monitor the survival of fhB7H3.CAR-Ts and evaluate the therapeutic efficacy. Additional follow-up and examination will be performed monthly for the first three month and then trimonthly until two year. Thereafter, annual follow-up will be completed for 5 years.
This is an investigator-initiated clinical study to assess clinical performance of novel fhB7H3.CAR-Ts which may help other advanced and recurrent liver cancer patients in the future.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatocellular Carcinoma
Keywords
Fully human B7H3 CAR-T, Recurrent Advanced Hepatocellular Carcinoma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
15 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
fhB7H3.CAR-T cells
Arm Type
Experimental
Arm Description
In phase I study , 9 enrolled patients diagnosed with advanced liver cancer will receive one-time transhepatic arterial infusion of fhB7H3.CAR-Ts at the doses of 1×10^6/kg, 3×10^6/kg and 5×10^6/kg, 3 patients for each dose. To further confirm the therapeutic efficacy, in phase II study, 6 enrolled patients will receive an optimal dose (balancing effectiveness and toxicity) of fhB7H3.CAR-Ts.
Intervention Type
Biological
Intervention Name(s)
fhB7H3.CAR-Ts
Other Intervention Name(s)
B7H3 targeting chimeric antigen receptor T cells
Intervention Description
fhB7H3.CAR-Ts will be transhepatic arterial infused after lymphodepletion. Three dose levels will be evaluated: Dose Level 1 (1×10^6/kg), dose Level 2 (3×10^6/kg) and dose Level 3 (5×10^6/kg). If dose limiting toxicities (DLTs) are observed in each doses, Dose Level -1 (0.5×10^6/kg /infusion) will be evaluated.
Intervention Type
Drug
Intervention Name(s)
Fludarabine
Other Intervention Name(s)
FLUDARA
Intervention Description
30 mg/m2 i.v. for 3 consecutive days (Day -5~Day -3)
Intervention Type
Drug
Intervention Name(s)
Cyclophosphamide
Other Intervention Name(s)
Cytoxan
Intervention Description
750 mg/m2 i.v. for once (Day -5)
Primary Outcome Measure Information:
Title
Safety of fhB7H3.CAR-T cells
Description
Adverse events, including the type, frequency, severity and duration, such as cytokine release syndrome (CRS), on-target off-tumor, immune effector cell-associated neurotoxicity syndrome, will be monitored and assessed.
Time Frame
1 month
Title
Objective response of fhB7H3.CAR-T cells
Description
Objective response rate (ORR) including complete response (CR), partial response (PR), and/or stable disease, will be determined by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria.
Complete Response (CR): disappearance of all target lesions, all target nodules must be reduced to normal size (short axis <10 mm).
Partial Response (PR): >=30% decrease in the sum of the longest diameter of target lesions. Stable Disease (SD): no response or less response than Partial or Progressive.
Progressive Disease (PD): 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
Time Frame
1 month
Secondary Outcome Measure Information:
Title
In vivo persistence of fhB7H3.CAR-T cells
Description
Presence of CAR T cells in the peripheral blood will be assessed.
Time Frame
1 month
Other Pre-specified Outcome Measures:
Title
Progress free survival (PFS)
Description
PFS will be assessed from the time of lymphodepletion prior to infusion of fhB7H3.CAR-Ts to progression (as defined per RECIST v1.1) or death.
Time Frame
up to 5 years
Title
Overall survival (OS)
Description
Description: OS will be assessed from the date of lymphodepletion prior to infusion of fhB7H3.CAR-Ts to the date of death.
Time Frame
up to 5 years
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:
Subjects should be 18-70 years old.
Subject has adequate performance status as defined by ECOG score of≤ 2.
Expected life expectancy is no less than 12 weeks.
Subjects must have histologically or cytologically confirmed unresectable, recurrent and / or metastatic hepatocellular carcinoma (HCC). And tumor tissues are measured positive for B7H3 expression.
Child-Pugh A, B grade.
Blood routine:
white blood cell count≥ 2.5 × 10^9 / L; hemoglobin≥ 9 g/dL; platelet count≥ 50 × 10^9 / L; lymphocyte proportion≥ 15 %;
Adequate organ function. Patients' main organs ( heart, lung, liver, kidney, etc. ) function well:
ALT and AST≤ 5 × ULN; ALB≥ 30 g/L； Total bilirubin≤ 2.5 × ULN； Serum creatinine< 220μmol/L; Indoor oxygen saturation ≥ 95 %; Left ventricular ejection fraction≥ 40%;
No allergic reaction to contrast agents.
Procurement and T-cell production eligibility: a previously evaluation confirmed autologous peripheral blood mononuclear cells can be used for T-cell production.
Patients or their legal guardians voluntarily participate in and sign the informed consent form.
Exclusion Criteria:
The subject is a pregnant or lactating woman.
The subjects have infectious diseases (such as HIV, syphilis, active tuberculosis, etc.);
The subject has active infection or coagulation dysfunction.
Subjects with previous hepatic encephalopathy.
The subject is on anticoagulation or antiplatelet therapy.
The subject is an organ transplant or waiting for transplant.
Subjects with mental or psychological diseases who cannot cooperate with treatment and efficacy evaluation.
The subjects are highly allergic or have a history of severe allergies.
The subject has received chemotherapy/radiotherapy within the past 4 weeks.
The subject has a history of cellular immunotherapy or antibody therapy.
The subject is receiving systemic hormone therapy.
Subjects with systemic infection or severe local infection requiring anti-infection treatment.
The subject has dysfunction of important organs such as heart, lung, brain, liver, and kidney.
The subject is participating in other clinical research.
The doctor believes that there are other reasons not to be included in the treatment.
Unwilling or unable to provide consent/assent for participation in the study.
Facility Information:
Facility Name
The Affiliated Hospital of Xuzhou Medical University
City
Xuzhou
State/Province
Jiangsu
ZIP/Postal Code
221002
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Yong Wang, M.D.
Phone
+86-516-83353391
Email
mumei20071115@163.com
First Name & Middle Initial & Last Name & Degree
Yan Li, M.D.
Phone
+86-516-83353391
Email
505620539@qq.com
First Name & Middle Initial & Last Name & Degree
Wei Xu, M.D.
First Name & Middle Initial & Last Name & Degree
Gang Wang, Ph.D.
12. IPD Sharing Statement
Plan to Share IPD
No
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Study Of B7H3 CAR-T Cells in Treating Advanced Liver Cancer
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