Clinical Study of CAIX-targeted CAR-T Cells in the Treatment of Advanced Renal Cell Carcinoma
Primary Purpose
Immunotherapy
Status
Recruiting
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
CAR-T cell immunotherapy
Sponsored by
About this trial
This is an interventional treatment trial for Immunotherapy focused on measuring Carbonic anhydrase, advanced renal cell carcinoma, CAR-T, Chimeric antigen receptor, T cell, CAIX
Eligibility Criteria
Inclusion Criteria:
- Male or female patients aged from 18 to 70 years old;
- The patient's ECOG score is ≤ 2;
- Patients with advanced or metastatic renal cell carcinoma:
(1) have received first-line and second-line targeted therapy in the past; (2) Previous immunization with PD-1/L1 and ≤2 regimens; (3) Unable to tolerate targeted therapy or immunotherapy. 4.There are measurable or evaluable lesions; 5.The main tissues and organs of patients function well:
- liver function: ALT/AST< 3 times the upper limit of normal value (ULN);
- Renal function: creatinine < 220 μmol/L;
- Lung function: indoor oxygen saturation ≥ 95%;
- Cardiac function: Left ventricular ejection fraction (LVEF)≥40% 6.Patients or their legal guardians voluntarily participate and sign informed consent.
Exclusion Criteria:
- Infectious diseases (such as HIV, active hepatitis B or C infection, active tuberculosis, etc.);
- Feasibility assessment and screening showed that the transfection of targeted lymphocytes was less than 10% or the amplification was insufficient (< 5 times) under the co-stimulation of CD3/CD28.
- The vital signs are abnormal, and those who cannot cooperate with the examination;
- Those who have mental or psychological diseases can not cooperate with treatment and efficacy evaluation;
- Highly allergic constitution or severe allergic history, especially those who are allergic to IL-2;
- Subjects with systemic infection or severe local infection who need anti-infection treatment;
- Complicated with dysfunction of heart, lung, brain, liver, kidney and other important organs;
- Patients with other tumors;
- Doctors believe that there are other reasons that can not be included in the treatment.
Sites / Locations
- Affiliated Hospital of Xuzhou Medical UniversityRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
CAR-T cell immunotherapy
Arm Description
The registered patients will received CAR-T cell immunotherapy for the new specific chimeric antigen receptor of CAIX antigen by infusion.
Outcomes
Primary Outcome Measures
Safety evaluation:Incidence and severity of adverse events
To evaluate the incidence and severity of possible adverse events within one month after targeted CAIX CAR-T infusion, including cytokine release syndrome and on-target toxicity.
Effectiveness evaluation
In order to observe the efficacy of CAR-T cells after infusion, total remission rate (ORR), complete remission (CR), partial remission (PR), disease stability (SD) or progression (PD) will be used for evaluation.
Secondary Outcome Measures
Progression-free survival (PFS)
Progression-free survival (PFS) time
Overall survival (OS)
Overall survival (OS) time
Full Information
NCT ID
NCT04969354
First Posted
July 4, 2021
Last Updated
July 17, 2021
Sponsor
The Affiliated Hospital of Xuzhou Medical University
Collaborators
Xuzhou Medical University
1. Study Identification
Unique Protocol Identification Number
NCT04969354
Brief Title
Clinical Study of CAIX-targeted CAR-T Cells in the Treatment of Advanced Renal Cell Carcinoma
Official Title
Clinical Study of CAIX-targeted CAR-T Cells in the Treatment of Advanced Renal Cell Carcinoma
Study Type
Interventional
2. Study Status
Record Verification Date
July 2021
Overall Recruitment Status
Recruiting
Study Start Date
October 1, 2021 (Anticipated)
Primary Completion Date
September 30, 2025 (Anticipated)
Study Completion Date
September 30, 2026 (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
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This is an experimental study to evaluate the safety and efficacy of CAR T cells targeting CAIX in the treatment of advanced renal cancer.
Detailed Description
We designed a clinical study and divided the trial into two phases.
Phase 1 (climbing test) : 12 patients were randomly divided into 4 groups (n=3). 12 patients were treated with cyclophosphamide at the dose of 60mg/kg/d 8-7 days before CAR-T cell infusion, and fludalabine at the dose of 25mg/m^2/d 6-2 days before CAR-T cell infusion. 5 mg anti-human CAIX monoclonal antibody (G250) was injected into the hepatic artery of each patient by an interventional catheter on the day before CAR-T cells infusion. On Day 0, CAR T cells were injected into patients in group 1, 2, 3 or 4 at the dose of 1x10^7/ person, 1*10^8/ person, 1*10^9/ person or 1*10^10/ person, respectively. The infusion time is about 15-30min. On day 0-14, IL-2 (75000IU/kg) was injected subcutaneously once a day. From day 15-28, IL-2 (75000IU/kg) was subcutaneously injected into the patients three times a week. The purpose of this study is to assess subjects' MTD (maximum tolerated dose) against CAR T cells.
Phase 2: After determining the appropriate therapeutic dose for patients with renal cell carcinoma, 8 patients received the same pre-treatment of chemotherapy and G250 antibody. Then, the appropriate therapeutic dose of CAR T cells according to the results of phase 1 was infused on Day 0. On day 0-14,IL-2 (75000IU/kg) was given subcutaneously once a day. On day 15-28, IL-2 (75000IU/kg) was given subcutaneously three times a week.
Peripheral blood was collected every 4 weeks to evaluate proliferation and survival of CAR-T cells. After 6 months of close follow-up, subjects will undergo a medical history evaluation, physical examination, and blood tests quarterly for 2 years. After this assessment, subjects will be enrolled in an annual telephone follow-up and questionnaire study for up to five years to evaluate treatment for long-term health problems, such as recurrence of malignant tumors.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Immunotherapy
Keywords
Carbonic anhydrase, advanced renal cell carcinoma, CAR-T, Chimeric antigen receptor, T cell, CAIX
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
20 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
CAR-T cell immunotherapy
Arm Type
Experimental
Arm Description
The registered patients will received CAR-T cell immunotherapy for the new specific chimeric antigen receptor of CAIX antigen by infusion.
Intervention Type
Biological
Intervention Name(s)
CAR-T cell immunotherapy
Intervention Description
This CAR-T cell immunotherapy with a novel specific Chimeric antigen receptor aiming at CAIX antigen.
Primary Outcome Measure Information:
Title
Safety evaluation:Incidence and severity of adverse events
Description
To evaluate the incidence and severity of possible adverse events within one month after targeted CAIX CAR-T infusion, including cytokine release syndrome and on-target toxicity.
Time Frame
First 1 month after CAR-T cells infusion
Title
Effectiveness evaluation
Description
In order to observe the efficacy of CAR-T cells after infusion, total remission rate (ORR), complete remission (CR), partial remission (PR), disease stability (SD) or progression (PD) will be used for evaluation.
Time Frame
3 months after CAR-T cells infusion
Secondary Outcome Measure Information:
Title
Progression-free survival (PFS)
Description
Progression-free survival (PFS) time
Time Frame
24 months after CAR-T cells infusion
Title
Overall survival (OS)
Description
Overall survival (OS) time
Time Frame
24 months after CAR-T cells infusion
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:
Male or female patients aged from 18 to 70 years old;
The patient's ECOG score is ≤ 2;
Patients with advanced or metastatic renal cell carcinoma:
(1) have received first-line and second-line targeted therapy in the past; (2) Previous immunization with PD-1/L1 and ≤2 regimens; (3) Unable to tolerate targeted therapy or immunotherapy. 4.There are measurable or evaluable lesions; 5.The main tissues and organs of patients function well:
liver function: ALT/AST< 3 times the upper limit of normal value (ULN);
Renal function: creatinine < 220 μmol/L;
Lung function: indoor oxygen saturation ≥ 95%;
Cardiac function: Left ventricular ejection fraction (LVEF)≥40% 6.Patients or their legal guardians voluntarily participate and sign informed consent.
Exclusion Criteria:
Infectious diseases (such as HIV, active hepatitis B or C infection, active tuberculosis, etc.);
Feasibility assessment and screening showed that the transfection of targeted lymphocytes was less than 10% or the amplification was insufficient (< 5 times) under the co-stimulation of CD3/CD28.
The vital signs are abnormal, and those who cannot cooperate with the examination;
Those who have mental or psychological diseases can not cooperate with treatment and efficacy evaluation;
Highly allergic constitution or severe allergic history, especially those who are allergic to IL-2;
Subjects with systemic infection or severe local infection who need anti-infection treatment;
Complicated with dysfunction of heart, lung, brain, liver, kidney and other important organs;
Patients with other tumors;
Doctors believe that there are other reasons that can not be included in the treatment.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Hailong Li, M.D/Ph.D
Phone
0086-17798835021
Email
Justinlee719@163.com
First Name & Middle Initial & Last Name or Official Title & Degree
Qing Zhang, Ph.D
Phone
0086-516-83262238
Email
qingzhang@xzhmu.edu.cn
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Junnian Zheng, M.D/Ph.D
Organizational Affiliation
The Affiliated Hospital of Xuzhou Medical University
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Hailong Li, M.D/Ph.D
Organizational Affiliation
The Affiliated Hospital of Xuzhou Medical University
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Qing Zhang, Ph.D
Organizational Affiliation
Xuzhou Medical University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Affiliated Hospital of Xuzhou Medical University
City
Xuzhou
State/Province
Jiangsu
ZIP/Postal Code
221000
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Hailong Li, M.D/Ph.D
Phone
0086-17798835021
Email
Justinlee719@163.com
12. IPD Sharing Statement
Plan to Share IPD
No
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Clinical Study of CAIX-targeted CAR-T Cells in the Treatment of Advanced Renal Cell Carcinoma
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