Back to resultsMesothelin-CAR-T Cells Against Cancers
Primary Purpose
Pancreas Cancer, CAR-T Cell Therapy, Mesothelin
Status
Recruiting
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
CAR-T cells
Sponsored by
About this trial
This is an interventional treatment trial for Pancreas Cancer focused on measuring Pancreas Cancer, CAR-T, Mesothelin, Solid Tumor
Eligibility Criteria
Inclusion Criteria: 1. Patients with advanced cancer that expresses Mesothelin protein; 2. Life expectancy >12 weeks; 3. Adequate heart, lung, liver, kidney, and blood function; 4. Available autologous transduced T cells with greater than or equal to 20% expression of Mesothelin-CAR determined by flow-cytometry and killing of Mesothelin-positive targets greater than or equal to 20% in cytotoxicity assay; 5. Informed consent explained to, understood by and signed by patient/guardian. Patient/guardian given copy of informed consent. - Exclusion Criteria: Had accepted gene therapy before; Severe virus infection such as HBV, HCV, HIV, et al; Known HIV positivity; Active infectious disease related to bacteria, virus,fungi,et al; Other severe diseases that the investigators consider not appropriate; Pregnant or lactating women; Systemic steroid treatment (greater than or equal to 0.5 mg prednisone equivalent/kg/day); Other conditions that the investigators consider not appropriate. -
Sites / Locations
- The Second Affiliated Hospital of Guangzhou Medical UniversityRecruiting
Outcomes
Primary Outcome Measures
Number of Patients with Dose Limiting Toxicity
A dose limiting toxicity is defined as any toxicity that is considered to be primarily related to the Mesothelin-CAR T cells, which is irreversible, or life threatening or hematologic or non-hematologic Grade 3-5.
Secondary Outcome Measures
Percent of Patients with best response as either complete remission or partial remission.
Response rates will be estimated as the percent of patients whose best response is either complete remission or partial remission by combining the data from the patients. To compare with historical data, a 95% confidence interval will be calculated for the response rate.
Median CAR-T cell persistence
Median CAR-T cell persistence will be measured by quantitative rt-PCR.
Full Information
NCT ID
NCT05779917
First Posted
March 10, 2023
Last Updated
March 10, 2023
Sponsor
Second Affiliated Hospital of Guangzhou Medical University
Collaborators
Fapon Biotherapy Inc.
1. Study Identification
Unique Protocol Identification Number
NCT05779917
Brief Title
Mesothelin-CAR-T Cells Against Cancers
Official Title
Mesothelin Targeted CAR-T for Immunotherapy of Pancreatic Cancer: Phase I Clinical Trial
Study Type
Interventional
2. Study Status
Record Verification Date
March 2023
Overall Recruitment Status
Recruiting
Study Start Date
March 10, 2023 (Actual)
Primary Completion Date
March 10, 2026 (Anticipated)
Study Completion Date
March 10, 2033 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Second Affiliated Hospital of Guangzhou Medical University
Collaborators
Fapon Biotherapy Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
Brief Summary
The second generation of mesothelin targeted CAR-T cells that secret a fusion protein of IL21 and scfv against PD1 have been constructed and their anti-cancer function has been verified by multiple in vitro and in vivo studies. Clinical studies will be performed to test anti-cancer function of the CAR-T cells for immunotherapy of human cancer patients with Mesothelin expressions. In this phase I study, the safety, tolerance, and preliminary efficacy of the Mesothelin-CAR-T cell immunotherapy on human cancers will firstly be evaluated.
Detailed Description
Choose appropriate patients with advanced pancreatic cancer or other cancers, with written consent for this study;
Perform biopsy to determine the expression of Mesothelin of the tumors by western blotting or IHC;
Collect blood from the patients and isolate mononuclear cells, activate the T cells and transfect the T cells with Mesothelin targeting CAR, amplify the transfected T cells as needed, test the quality and killing activity of the CAR-T cells and then transfer them back the patients via systemic or local injections, and follow up closely to collect related results as required;
To enhance the killing capability, cotreatment the patients with PD1/PDL1/CTLA4 antibodies may be applied;
Evaluate the clinical results as needed.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pancreas Cancer, CAR-T Cell Therapy, Mesothelin, Solid Tumor, Adult
Keywords
Pancreas Cancer, CAR-T, Mesothelin, Solid Tumor
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Model Description
Use engineered CAR-T cells to kill cancer cells with mesothelin overexpression.
Masking
None (Open Label)
Allocation
N/A
Enrollment
30 (Anticipated)
8. Arms, Groups, and Interventions
Intervention Type
Biological
Intervention Name(s)
CAR-T cells
Intervention Description
Transfer CAR-T cells into patients for anti-ancer therapy.
Primary Outcome Measure Information:
Title
Number of Patients with Dose Limiting Toxicity
Description
A dose limiting toxicity is defined as any toxicity that is considered to be primarily related to the Mesothelin-CAR T cells, which is irreversible, or life threatening or hematologic or non-hematologic Grade 3-5.
Time Frame
six months
Secondary Outcome Measure Information:
Title
Percent of Patients with best response as either complete remission or partial remission.
Description
Response rates will be estimated as the percent of patients whose best response is either complete remission or partial remission by combining the data from the patients. To compare with historical data, a 95% confidence interval will be calculated for the response rate.
Time Frame
six months
Title
Median CAR-T cell persistence
Description
Median CAR-T cell persistence will be measured by quantitative rt-PCR.
Time Frame
Six years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
1. Patients with advanced cancer that expresses Mesothelin protein; 2. Life expectancy >12 weeks; 3. Adequate heart, lung, liver, kidney, and blood function; 4. Available autologous transduced T cells with greater than or equal to 20% expression of Mesothelin-CAR determined by flow-cytometry and killing of Mesothelin-positive targets greater than or equal to 20% in cytotoxicity assay; 5. Informed consent explained to, understood by and signed by patient/guardian. Patient/guardian given copy of informed consent.
-
Exclusion Criteria:
Had accepted gene therapy before;
Severe virus infection such as HBV, HCV, HIV, et al;
Known HIV positivity;
Active infectious disease related to bacteria, virus,fungi,et al;
Other severe diseases that the investigators consider not appropriate;
Pregnant or lactating women;
Systemic steroid treatment (greater than or equal to 0.5 mg prednisone equivalent/kg/day);
Other conditions that the investigators consider not appropriate. -
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Zhenfeng Zhang, MD, PhD
Phone
0086-020-39195965
Email
zhangzhf@gzhmu.edu.cn
First Name & Middle Initial & Last Name or Official Title & Degree
Bingjia He, MD
Phone
+862039195965
Email
464677938@qq.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Zhenfeng Zhang, MD, PhD
Organizational Affiliation
Second Affiliated Hospital of Guangzhou Medical University
Official's Role
Principal Investigator
Facility Information:
Facility Name
The Second Affiliated Hospital of Guangzhou Medical University
City
Guangzhou
State/Province
Guangdong
ZIP/Postal Code
510260
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Zhenfeng Zhang, MD, PHD
Phone
+862039195966
Email
zhangzhf@gzhmu.edu.cn
12. IPD Sharing Statement
Plan to Share IPD
Undecided
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Mesothelin-CAR-T Cells Against Cancers
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