Clinical trial NCT06355908: IL13Rα2 CAR-T for Patients With r/r Glioma
Official title: Safety, Tolerability and Efficacy of Enhanced IL-13Rα2 Targeted Chimeric Antigen Receptor T Cell Immunotherapy Against Recurrent/Refractory Grade 4 Glioma
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Glioma
Keywords: r/r WHO4 glioma
Lead sponsor: Beijing Tiantan Hospital
Sponsor class: OTHER
Collaborators: name: TCRCure Biopharma Ltd.
First posted: 2024-04-10
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Safety of IL13Rα2 CAR-T
timeFrame: Day 0 - Day 730
Secondary outcomes:
measure: Overall Response Rate (ORR)
timeFrame: Day 0 - Day 730
measure: Duration of Response (DOR)
timeFrame: Day 0 - Day 730
measure: Progression Free Survival (PFS)
timeFrame: Day 0 - Day 730
measure: Overall Survival (OS)
timeFrame: Day 0 - Day 730
measure: Overall Survival (OS) at 6 months (OS6)
timeFrame: Day 0 - Day 180
measure: Overall Survival (OS) at 12 months (OS12)
timeFrame: Day 0 - Day 365
measure: The levels of IL13Rα2 CAR-T cell and IL13Rα2 CAR in the CSF and peripheral blood
timeFrame: Day 0 - Day 730
measure: The levels of cytokines in the CSF and peripheral blood
timeFrame: Day 0 - Day 730
Other outcomes:
measure: The Exploratory Indicators
timeFrame: Day 0 - Day 730
Locations:
city: Beijing
country: China
facility: Beijing Tiantan Hospital
Study officials:
affiliation: Beijing Tiantan Hospital
name: Nan Ji, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Beijing Tiantan Hospital
name: Yang Zhang
role: PRINCIPAL_INVESTIGATOR
References: