A Clinical Study of IL13Rα2 Targeted CAR-T in Patients With Malignant Glioma (MAGIC-I)

Sponsor

CellabMED (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05540873

Collaborator

(none)

Enrollment

Location

Arm

21.4

Anticipated Duration (Months)

0.8

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a phase I study to evaluate the safety and tolerability of IL13Rα2 Targeted Chimeric Antigen Receptor-T Cell in patients with Refractory or Recurrent Malignant Glioma and to evaluate the changes of AE incidence.

Condition or Disease	Intervention/Treatment	Phase
Recurrent Malignant Glioma	Drug: YYB-103	Phase 1

Detailed Description

This is a single-center, single-arm, open-label phase 1 study that will follow a 3 + 3 design of dose-escalating cohorts. The objectives of this study is to assess the safety and tolerability after administration of YYB-103 (IL13Rα2 targeted CAR-T cell) in patients with malignant glioma.

YYB-103 is designed to target cancer cells expressing IL13Rα2 in cell surface. Only those subjects who are expressing IL13Rα2 and satisfy the inclusion and exclusion criteria will receive IV infusion of YYB-103.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

18 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Single-center, Single-arm, Open-label Phase 1 Clinical Trial to Assess the Safety and Tolerability of YYB-103, IL13Rα2 Targeted Chimeric Antigen Receptor-T Cell (CAR-T) in Treating Patients With Refractory or Recurrent Malignant Glioma

Actual Study Start Date :

Jul 18, 2022

Anticipated Primary Completion Date :

Feb 28, 2024

Anticipated Study Completion Date :

Apr 30, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: IL13Rα2 targeted CAR-T	Drug: YYB-103 Biological: IL13Rα2 CAR-T cells Administration method: intravenous infusion YYB-103 is manufactured according to the subject's assigned dose group and body weight.

Arm

Intervention/Treatment

Experimental: IL13Rα2 targeted CAR-T

Drug: YYB-103

Biological: IL13Rα2 CAR-T cells Administration method: intravenous infusion YYB-103 is manufactured according to the subject's assigned dose group and body weight.

Outcome Measures

Primary Outcome Measures

Dose Limiting Toxicity (DLT) [28 days after IP administration]
Maximum Tolerance Dose (MTD) [28 days after IP administration]
Recommended Phase 2 Dose (RP2D) [28 days after IP administration]

Secondary Outcome Measures

Adverse event [Baseline up to 3 months]
Cytokine Release Syndrome (CRS) and Immune effector Cell-Associated Neurotoxicity Syndrome(ASTCT consensus grading) / The others(CTCAE criteria)
Cytokine test [Baseline up to 3 months]
Pheripheral blood
Tumor response assessment(iRANO criteria) [Baseline up to 3 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

19 Years to 74 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria

Primary inclusion criteria (Screening criteria)

: Only subjects who meet all of the following conditions conduct examinations and tests including the IHC and PBMC

Provision of voluntary written consent to participate in this clinical trial
Male and female aged ≥ 19 years to <75 years
Patients with histologically or cytologically confirmed progressive malignant glioma (Grade III or IV according to the WHO criteria) and histological and/or radiologic data to confirm that it is refractory or recurrent (applicable to 'Progression Disease (PD)' according to the Response Assessment for Neuro-Oncology (RANO) criteria for high grade gliomas defined by the Society for Neuro-Oncology) despite treatment applicable to the standard treatment for each stage
Subject with the Karnofsky Performance Status (KPS) Scale ≥ 60
Subject with the life expectancy of least 12 weeks at the investigator's discretion
Subject who satisfies the following treatment condition, regardless of the previous line of treatment
At least 12 weeks after completion of the last anticancer radiation treatment
Other cell toxicity therapy not mentioned above: At least 3 weeks have passed
Non-cytotoxic agent (e.g., interferon, tamoxifen, etc.): At least 1 week has passed
Completion of treatment of all toxicities and AEs (other than alopecia and vitiligo) due to the previous treatment

Secondary Inclusion Criteria (Eligibility Criteria)

Subjects confirmed as positive for IL13Rα2 expression from immunostaining (IHC)
Subjects with Peripheral Blood Monocyte Count ≥ 7.5x10^5 cells/5 ml from the PBMC test
Subjects with appropriate bone marrow, liver, and kidney function by satisfying all of the following in clinical laboratory tests
WBC ≥ 2,000/μl
ANC ≥ 1,000/μl
Platelet count ≥ 75,000/μl
Hemoglobin ≥ 8.0 g/dL
ALT/AST ≤ 2.5 x ULN
Serum creatinine ≤ 1.5 x ULN
Total bilirubin ≤ 1.5 x ULN

Exclusion Criteria

Primary Exclusion Criteria (Screening criteria)

Subjects diagnosed with ventricular seeding, spinal drop metastasis, or leptomeningeal metastasis from radiologic testing obtained at screening
Subjects with findings of immunodeficiency, autoimmune disease (e.g.; rheumatoid arthritis, systemic lupus erythematosus, vasculitis, multiple sclerosis, etc.) or inflammatory disease
Subjects with significant active cardiovascular disease including the following
Uncontrolled hypertension (SBP >180 mmHg or DBP >110 mmHg), unstable angina, pulmonary embolism, cerebrovascular disease, valvular disease, cardiac failure, or myocardial infarction or serious cardiac arrhythmia within the past 6 months
Subjects with a medical history of malignant tumor other than the study indication within 5 years of screening (however, within 3 years of screening in case of malignant tumor (e.g., appropriately treated cervical carcinoma in situ, basal or squamous cell skin cancer, localized prostate cancer, ductal carcinoma in situ, etc.) with minimal risk of metastasis/recurrence and death)
Subjects who continuously used systemic immunosuppressants (including but not limited to cyclophosphamide, azathioprine, methotrexate, and thalidomide) other than steroids within 2 weeks of screening
Subjects on systemic steroids who received a dose exceeding dexamethasone 6 mg/day (or equivalent dose) within 1 week of screening(note that topical steroids, inhaled steroid, and use of transient steroids for prevention of vomiting prior to anticancer agents administration are acceptable)
Subjects with a history of previously using an immune cell therapy agent
Subjects with a medical history of severe allergy, anaphylaxis, or other hypersensitivity reaction to the chimeric or humanized antibody or fusion protein
Subjects who participated in other clinical trial (medicinal product or medical device) within 4 weeks of screening
Women of childbearing potential and men who have a plan to get pregnant until 3 months after investigational product administration, are not willing to practice appropriate contraception method*, or are not willing to maintain abstinence from sexual intercourse

Hormonal contraception method, intrauterine device (IUD) or intrauterine system (IUS), surgical sterilization of the subject or partner, tubal ligation, double barrier method (a combined use of a barrier method such as a female condom, cervical cap, contraceptive diaphragm, or contraceptive sponge with a male condom), single barrier method combined with spermicide)

Pregnant women or breastfeeding mothers
Subjects who are determined by the investigator to be ineligible as subjects of this clinical trial for other reason

Secondary Exclusion Criteria (Eligibility Criteria)

Subjects who are positive to any of the following virus test results at screening
Hepatitis B virus surface antigen (HBsAg)
Hepatitis C virus antibody test (anti-HCV Ab)
HIV antibody test (anti-HIV)
Subjects who are determined by the investigator to be ineligible as subjects of this clinical trial for other reason