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Safety and Efficacy of Targeted IL-13 Rα2 or B7-H3 UCAR-T for Advanced Glioma

Primary Purpose

Advanced Glioma, Complication of Chimeric Antigen Receptor (CAR-T) Cell Therapy

Status
Recruiting
Phase
Not Applicable
Locations
China
Study Type
Interventional
Intervention
Targeted IL-13 Rα2 UCAR-T cell injection
Targeted B7-H3 UCAR-T cell injection
Sponsored by
Second Affiliated Hospital of Soochow University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Advanced Glioma

Eligibility Criteria

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

Inclusion Criteria: 18-70 years old, male or female, and the expected survival period is not less than 3 months. Advanced, locally advanced or recurrent tumor diagnosed histologically or cytologically. Failed in previous standard treatment or gived up treatment for various reasons after failure of first-line treatment. Failed in therapy by PD-1 or PD-L1 antibody or stopped administration of PD-1 or PD-L1 antibody for more than 4 weeks. At least 1 measurable target lesion (RECIST v1.1). 0-2 in ECOG physical state score. Available initial or recurrent tumor tissue for at least 10 stanable and detectable sections. Blood routine test: WBC ≥ 3×10^9/L, lymphocyte percentage (LY%) ≥ 15%, hemoglobin Hbo (Hb) ≥ 90g/L, platelet (PLT) ≥ 60×10^9/L. Liver and kidney functions: alanine transaminase (ALT) and aspartate transaminase (AST) < 3 times of the normal value, total bilirubin (TBiL) < 1.5 times of the normal value, serum creatinine (SCR) < 1.5 times of the normal value. IL-13Rα2 or B7-H3 antigen expression > 50%. Volunteered to enroll this study and signed the informed consent with good compliance and cooperation with follow-up. Experienced radiotherapy and chemotherapy with an interval of more than 4 week. Exclusion Criteria: Hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) positive and peripheral blood HBV DNA titer ≥ 5 × 10^2 copies/L; HCV antibody and peripheral blood HCV RNA positive; Human immunodeficiency virus (HIV) antibody positive; CMV DNA test positive; Syphilis test positive. Experienced any gene therapy previously. Needing long-term immunosuppressants for any reason. Any serious and uncontrolled systemic autoimmune disease or any unstable systemic disease, including but not limited to systemic lupus erythematosus, rheumatoid arthritis, ulcerative colitis, Crohn's disease and temporal arteritis. Severe heart, lung, liver and kidney insufficiency or severe debilitating lung disease; Cardiac function: Grade III or above according to NYHA standard; Liver function: grade C in Child-Puge grading standard; Renal function: chronic kidney disease (CKD) more than stage 4; Renal insufficiency above stage Ⅲ; Lung function: symptoms of severe respiratory failure, involving other organs; Brain function: abnormality of central nervous system or disturbance of consciousness. Administrating of systematical steroids currently (except usage inhaled steroids recently or currently). Pregnancy and lactation (the safety of this treatment for unborn children is not clear, and female participants with reproductive potential must have negative serum or urine pregnancy test within 48 hours before administration). Allergy to immunotherapy and related drugs. Complicated with another tumor. History of organ transplantation or waiting for organ transplantation. After evaluation by researcher,noncompliance with the requirements of the study protocol was confirmed.

Sites / Locations

  • The Second Affiliated Hospital of Soochow UniversityRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Interventional Group

Arm Description

Outcomes

Primary Outcome Measures

Objective Response Rate
The proportion of patients whose tumor size decreases to the expected value and can continue to meet the expected minimum time limit。

Secondary Outcome Measures

Progression-Free Survival
The time from enrolling into the trial to the first occurrence of disease progression or death from any cause。

Full Information

First Posted
February 20, 2023
Last Updated
March 2, 2023
Sponsor
Second Affiliated Hospital of Soochow University
Collaborators
Soochow T-Maximun Biotechnology Co. LTD
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1. Study Identification

Unique Protocol Identification Number
NCT05752877
Brief Title
Safety and Efficacy of Targeted IL-13 Rα2 or B7-H3 UCAR-T for Advanced Glioma
Official Title
Clinical Study on Evaluation of Safety and Efficacy of Targeted IL-13 Rα2 or B7-H3 UCAR-T Cell Injection in Treatment of Advanced Glioma
Study Type
Interventional

2. Study Status

Record Verification Date
February 2023
Overall Recruitment Status
Recruiting
Study Start Date
May 1, 2021 (Actual)
Primary Completion Date
April 30, 2026 (Anticipated)
Study Completion Date
April 30, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Second Affiliated Hospital of Soochow University
Collaborators
Soochow T-Maximun Biotechnology Co. LTD

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 goal of this clinical trial is to estimate the safety, tolerance and initial efficacy of target IL-13Rα2 or B7-H3 UCAR-T cell injection in the treatment of patients with advanced glioma, as well as the pharmacokinetic characteristics of its metabolites after single and multiple administrations and the biomarkers related to efficacy, safety and drug metabolism.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Advanced Glioma, Complication of Chimeric Antigen Receptor (CAR-T) Cell Therapy

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
12 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Interventional Group
Arm Type
Experimental
Intervention Type
Biological
Intervention Name(s)
Targeted IL-13 Rα2 UCAR-T cell injection
Intervention Description
local administration (intracranial cavity or intravertebral injection after surgery): 1 ampoule (about 2-5 ml, 1-5×10^7 cells) for 1-2 minutes each time.
Intervention Type
Biological
Intervention Name(s)
Targeted B7-H3 UCAR-T cell injection
Intervention Description
local administration (intracranial cavity or intravertebral injection after surgery): 1 ampoule (about 2-5 ml, 1-5×10^7 cells) for 1-2 minutes each time.
Primary Outcome Measure Information:
Title
Objective Response Rate
Description
The proportion of patients whose tumor size decreases to the expected value and can continue to meet the expected minimum time limit。
Time Frame
Up to 5 years or complete the follow-up of the last enrolled patient, whichever comes first.
Secondary Outcome Measure Information:
Title
Progression-Free Survival
Description
The time from enrolling into the trial to the first occurrence of disease progression or death from any cause。
Time Frame
Up to 5 years or complete the follow-up of the last enrolled patient, whichever comes first.

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: 18-70 years old, male or female, and the expected survival period is not less than 3 months. Advanced, locally advanced or recurrent tumor diagnosed histologically or cytologically. Failed in previous standard treatment or gived up treatment for various reasons after failure of first-line treatment. Failed in therapy by PD-1 or PD-L1 antibody or stopped administration of PD-1 or PD-L1 antibody for more than 4 weeks. At least 1 measurable target lesion (RECIST v1.1). 0-2 in ECOG physical state score. Available initial or recurrent tumor tissue for at least 10 stanable and detectable sections. Blood routine test: WBC ≥ 3×10^9/L, lymphocyte percentage (LY%) ≥ 15%, hemoglobin Hbo (Hb) ≥ 90g/L, platelet (PLT) ≥ 60×10^9/L. Liver and kidney functions: alanine transaminase (ALT) and aspartate transaminase (AST) < 3 times of the normal value, total bilirubin (TBiL) < 1.5 times of the normal value, serum creatinine (SCR) < 1.5 times of the normal value. IL-13Rα2 or B7-H3 antigen expression > 50%. Volunteered to enroll this study and signed the informed consent with good compliance and cooperation with follow-up. Experienced radiotherapy and chemotherapy with an interval of more than 4 week. Exclusion Criteria: Hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) positive and peripheral blood HBV DNA titer ≥ 5 × 10^2 copies/L; HCV antibody and peripheral blood HCV RNA positive; Human immunodeficiency virus (HIV) antibody positive; CMV DNA test positive; Syphilis test positive. Experienced any gene therapy previously. Needing long-term immunosuppressants for any reason. Any serious and uncontrolled systemic autoimmune disease or any unstable systemic disease, including but not limited to systemic lupus erythematosus, rheumatoid arthritis, ulcerative colitis, Crohn's disease and temporal arteritis. Severe heart, lung, liver and kidney insufficiency or severe debilitating lung disease; Cardiac function: Grade III or above according to NYHA standard; Liver function: grade C in Child-Puge grading standard; Renal function: chronic kidney disease (CKD) more than stage 4; Renal insufficiency above stage Ⅲ; Lung function: symptoms of severe respiratory failure, involving other organs; Brain function: abnormality of central nervous system or disturbance of consciousness. Administrating of systematical steroids currently (except usage inhaled steroids recently or currently). Pregnancy and lactation (the safety of this treatment for unborn children is not clear, and female participants with reproductive potential must have negative serum or urine pregnancy test within 48 hours before administration). Allergy to immunotherapy and related drugs. Complicated with another tumor. History of organ transplantation or waiting for organ transplantation. After evaluation by researcher,noncompliance with the requirements of the study protocol was confirmed.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Qing Lan, Doctor
Phone
+86-512-67784087
Email
szlq006@163.com
First Name & Middle Initial & Last Name or Official Title & Degree
Qing Zhu, Doctor
Phone
+86-512-67784086
Email
suzhouneurosurgeon@126.com
Facility Information:
Facility Name
The Second Affiliated Hospital of Soochow University
City
Suzhou
State/Province
Jiangsu
ZIP/Postal Code
215004
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Qing Lan, Doctor
Phone
051267784087
Email
szlq006@163.com

12. IPD Sharing Statement

Learn more about this trial

Safety and Efficacy of Targeted IL-13 Rα2 or B7-H3 UCAR-T for Advanced Glioma

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