IL13Rα2 CAR-T for Patients With r/r Glioma

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

Status

Suspended

Phases

Phase 1

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT06355908

Acronym

ENHANCING

Enrollment

Registered

2024-04-10

Start date

2024-03-21

Completion date

2027-05-01

Last updated

2026-01-20

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Glioma

Keywords

r/r WHO4 glioma

Brief summary

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

Detailed 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.

Interventions

BIOLOGICALIL13Rα2 CAR-T

The IL13Rα2 CAR-T cells will be administered via intraventricular infusion every 2 weekly via an Ommaya reservoir.

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to 75 Years

Healthy volunteers

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 IL13Rα2 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.

Design outcomes

Primary

Measure	Time frame	Description
Safety of IL13Rα2 CAR-T	Day 0 - Day 730	The safety of IL13Rα2 CAR-T will be assessed based on the totality of dose-limiting toxicity (DLT) and adverse event (AE) data collected during this phase.

Secondary

Measure	Time frame	Description
Overall Response Rate (ORR)	Day 0 - Day 730	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.
Duration of Response (DOR)	Day 0 - Day 730	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.
Progression Free Survival (PFS)	Day 0 - Day 730	To evaluate the time from the date of the first CAR-T infusion until disease progression per iRANO or death due to any cause.
Overall Survival (OS)	Day 0 - Day 730	To evaluate the time from the date of the first CAR-T infusion to death due to any cause.
Overall Survival (OS) at 6 months (OS6)	Day 0 - Day 180	To evaluate the percentage of survival subjects at 6 months after the first CAR-T infusion.
Overall Survival (OS) at 12 months (OS12)	Day 0 - Day 365	To evaluate the percentage of survival subjects at 12 months after the first CAR-T infusion.
The levels of IL13Rα2 CAR-T cell and IL13Rα2 CAR in the CSF and peripheral blood	Day 0 - Day 730	To detect the levels of IL13Rα2 CAR-T cell and IL13Rα2 CAR in the CSF and peripheral blood.
The levels of cytokines in the CSF and peripheral blood	Day 0 - Day 730	To detect levels of cytokines in the CSF and peripheral blood, cytokines will include IL-2, IL-6, IFN-γ, TNF-α, etc.

Countries

China

Contacts

PRINCIPAL_INVESTIGATORNan Ji, MD, PhD

Beijing Tiantan Hospital

PRINCIPAL_INVESTIGATORYang Zhang