Recurrent Malignant Glioma
Conditions
Keywords
Chimeric antigen receptor, Malignant glioma, IL13Rα2, CLM_103_MG001, YYB103, MAGIC-I
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. And this study have to long term follow-up.
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. Long term follow-up study is evaluate the safety and exploratory efficacy of IP for 15 years from the date of IP administration in patients with malignant glioma refractory or recurrent to standard therapy who participated in this study. Subjects who participated in the Phase 1 study and received YYB-103 must have long-term follow-up for 15 years from the date of administration. During the long-term follow-up period, AEs, exploratory efficacy etc. are observed, and the observation period is every 6 months within 5 years and then yearly until 15 years.
Interventions
DRUGYYB-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.
Sponsors
CellabMED
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
19 Years to 74 Years
Healthy volunteers
No
Inclusion criteria
1. 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 2. 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
1. Primary
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| Disease response (DCR) | Baseline up to 6 months | Tumor response will be assessed by comparison with baseline magnetic resonance imaging by iRANO criteria. Evaluation of DCR is the proportion of subjects with CR or PR or SD as a result of tumor response assessment. |
| Pharmacokinetics and cytokine levels | 3 months, up to 15 years if necessary | Peripheral blood (PB) and Cerebral spinal fluid (CSF) |
| Incidence of AE | 3 months, up to 15 years if necessary | CRS and ICANS (ASTCT) / Others (CTCAE V5.0) |
| RCR | 1 year, up to 15 years if necessary | RCR formation will be checked by collecting samples at 3M, 6M, and every 6 months thereafter until 5 years from IP administration, and then will be followed up annually thereafter until 15 years from IP administration via medical history without collecting samples. If all RCR test results are negative for 1 year after IP administration, sample collection will be stopped, and annual follow-up. |
Countries
South Korea
Contacts
Primary ContactSungmin Jun
Outcome results
None listed