IL13Rα2 CAR-T for Patients With r/r Glioma

Glioma Clinical Trial

— ENHANCING  

Official title:

Safety, Tolerability and Efficacy of Enhanced IL-13Rα2 Targeted Chimeric Antigen Receptor T Cell Immunotherapy Against Recurrent/Refractory Grade 4 Glioma

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06355908
• Other study ID #: TT002
• Status: Recruiting
• Phase: Phase 1
• Start date: March 21, 2024
• Est. completion date: May 1, 2027

Study information

• Verified date: June 2024
• Source: Beijing Tiantan Hospital
• Contact: Yang Zhang, MD, PhD
• Phone: +861059976516
• Email: zhangyang8025[@]yeah.net
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a dose exploration clinical trial to assess the safety and feasibility of the IL13Ra2-targeted CAR-T in glioma.

Description:

Interleukin 13 receptor subunit alpha-2 (IL13Ra2A) is a high-affinity membrane receptor of the anti-inflammatory Th2 cytokine IL13, which is overexpressed in glioma and correlated with poor prognosis.

Chimeric antigen receptor (CAR) T cell therapy is a promising treatment approach for many malignancies. IL13Ra2-targeted CAR-T cells are under investigation in several clinical trials in primary CNS malignancies.

The investigators now designed a new structure CAR targeted IL13Ra2, and initiated a single arm, open, dose exploration clinical trial to evaluate the safety, tolerability, clinical efficacy, and pharmacokinetic characteristics of IL13Rα2 CAR-T for patients with glioma. This clinical trial will enroll 12-30 cases of patients with IL13α2-positive recurrent or refractory WHO grade 4 glioma (r/r WHO4 glioma), aiming to find the maximum tolerable dose (MTD), the recommended phase 2 dose (RP2D) and preliminary efficacy of the new structure IL13Ra2 CAR-T.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: May 1, 2027
• Est. primary completion date: May 1, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion criteria:

1. Male or female aged 18-75 years (including 18 and 75 years old).

2. Karnofsky scale score (KPS)=50.

3. Subjects with WHO grade 4 gliomas who have relapsed or progressed during or after standard treatments such as surgery, radiotherapy, and chemotherapy.

4. Tumor with IL13Ra2 positive expression.

5. Availability in collecting peripheral blood mononuclear cells (PBMCs).

6. Adequate laboratory values and adequate organ function.

7. Patients with childbearing/fathering potential must agree to use highly effective contraception.

Exclusion criteria:

1. Pregnant or breastfeeding females.

2. Contraindication to bevacizumab.

3. Within 5 days prior to the infusion of CAR-T cells, subjects receiving systemic administration of steroids with dosage more than 10mg/d prednisone or the equivalent doses of other steroids (not including inhaled corticosteroid).

4. Comorbid with other uncontrolled malignancy.

5. Active immunodeficiency virus (HIV) or hepatitis B virus or hepatitis C virus or tuberculosis infection.

6. Autoimmune diseases.

7. Severe or uncontrolled psychiatric diseases or condition that could increase adverse events or interfere the evaluation of outcomes.

8. Subjects who have previously received cell therapy (such as TCR-T, CAR-T, TIL, etc.).

9. Subjects with other conditions that would interfere trial participation at the investigator's discretion.

Related Conditions & MeSH terms

• Glioma

Intervention

Biological:
• IL13Ra2 CAR-T
The IL13Ra2 CAR-T cells will be administered via intraventricular infusion every 2 weekly via an Ommaya reservoir.

Locations

Country	Name	City	State
China	Beijing Tiantan Hospital	Beijing

Sponsors (2)

Lead Sponsor	Collaborator
Yang Zhang	TCRCure Biopharma Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	The Exploratory Indicators	To analyze tumor microenvironment and CAR-T cell infiltrative levels in tumor tissues before and after treatment by immunohistochemistry and/or transcriptome sequencing, and explore the tumor or immune cell markers related to disease prognosis and IL13Ra2 expression.	Day 0 - Day 730
Primary	Safety of IL13Ra2 CAR-T	The safety of IL13Ra2 CAR-T will be assessed based on the totality of dose-limiting toxicity (DLT) and adverse event (AE) data collected during this phase.	Day 0 - Day 730
Secondary	Overall Response Rate (ORR)	To evaluate the percentage of subjects who have a confirmed partial response (PR) and complete response (CR) per immunotherapy response assessment in neuro-oncology (iRANO) criteria.	Day 0 - Day 730
Secondary	Duration of Response (DOR)	To evaluate the duration from the time that criteria are met for CR or PR per iRANO until disease progression or death due to any cause.	Day 0 - Day 730
Secondary	Progression Free Survival (PFS)	To evaluate the time from the date of the first CAR-T infusion until disease progression per iRANO or death due to any cause.	Day 0 - Day 730
Secondary	Overall Survival (OS)	To evaluate the time from the date of the first CAR-T infusion to death due to any cause.	Day 0 - Day 730
Secondary	Overall Survival (OS) at 6 months (OS6)	To evaluate the percentage of survival subjects at 6 months after the first CAR-T infusion.	Day 0 - Day 180
Secondary	Overall Survival (OS) at 12 months (OS12)	To evaluate the percentage of survival subjects at 12 months after the first CAR-T infusion.	Day 0 - Day 365
Secondary	The levels of IL13Ra2 CAR-T cell and IL13Ra2 CAR in the CSF and peripheral blood	To detect the levels of IL13Ra2 CAR-T cell and IL13Ra2 CAR in the CSF and peripheral blood.	Day 0 - Day 730
Secondary	The levels of cytokines in the CSF and peripheral blood	To detect levels of cytokines in the CSF and peripheral blood, cytokines will include IL-2, IL-6, IFN-?, TNF-a, etc.	Day 0 - Day 730