High-grade Glioma
Conditions
Keywords
MT027, High-grade glioma
Brief summary
The clinical protocol plans to preset three dose groups, namely 1×10⁷ cells per dose, 3×10⁷ cells per dose, and 6×10⁷ cells per dose. The injection will be administered once every three weeks, adopting a 3 + 3 dose escalation design. The dosing interval is based on the pharmacokinetic (PK), safety and preliminary efficacy data of MT027 investigator-initiated trial (IIT) previously conducted at Dushu Lake Hospital of Soochow University. Accordingly, it is recommended to maintain the dosing interval of once every three weeks, with a window period of ±7 days. According to past experience, the dosing cycle should be at least 6 cycles, with each cycle lasting 21 days. If patients still benefit after more than 6 cycles, they can continue to receive the medication until no further benefit is achieved. The number of treatment sessions is approximately 6 to 9 times. However, the specific number of treatment sessions will generally be determined by the investigator based on the patient's disease condition.
Interventions
MT027: CRISPR/Cas9 edited B7H3-specific allogeneic CAR-T cells
Sponsors
Suzhou Maximum Bio-tech Co., Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
1. Voluntarily participate in this study and sign the informed consent form. 2. Be aged between 18 and 70 years old (including the critical values), with no gender limitation. 3. Subjects with high-grade glioma diagnosed pathologically (referring to grade 3 or 4 in the WHO (2021) Classification of Tumors of the Central Nervous System), who have progressive disease during standard treatment or have recurrence after standard treatment. 4. Enhanced MRI shows space-occupying lesions in the brain, and there is at least one measurable lesion (according to the iRANO 2010 version criteria). 5. The tumor tissue of the patient has positive expression of B7-H3. The subject voluntarily provides the most recent formalin-fixed paraffin-embedded (FFPE) tissue or pathological sections (at least 8 consecutive blank sections) for the detection of B7-H3 expression (immunohistochemistry, IHC). 6. Have an expected survival period of ≥ 3 months. 7. Have a Karnofsky Performance Scale (KPS) score of ≥ 70 points. -
Exclusion criteria
1\. Patients with recurrence in the brainstem, spinal cord dissemination or extracranial metastasis; 2. The maximum diameter of a single tumor lesion is \> 5 cm, or the cumulative maximum diameter of multiple lesions is \> 6 cm; 3. Having received radiotherapy within 3 months before cell therapy or having received surgical treatment (except for Ommaya reservoir implantation), chemotherapy (except for lymphocyte depletion therapy), immunotherapy, molecular targeted therapy or any other anti-tumor therapy within 4 weeks before cell therapy; 4. Having participated in other drug clinical trials within 4 weeks before screening; 5. Having previously received CAR-T cell therapy; 6. Subjects with a severe allergy history to any component of the experimental drug or biological products; 7. Subjects with other primary malignancies (except for cured cervical carcinoma in situ and basal cell carcinoma of the skin); 8. Suffering from major diseases such as active systemic infection and coagulation disorders; 9. Suffering from severe insufficiency of heart, lung, liver and kidney functions; cardiac function: grade III or above according to the New York Heart Association (NYHA) criteria; liver function: grade C or above according to the Child-Pugh grading criteria; renal function: chronic kidney disease (CKD) stage 4 or above; renal insufficiency stage III or above; pulmonary function: severe respiratory failure symptoms involving other organs; 10. Subjects with severe autoimmune diseases; 11. Subjects who have previously received allogeneic tissue/solid organ transplantation; 12. Subjects who have received live vaccines within 2 weeks before the first cell therapy or who plan to receive live vaccines during the study period; 13. Subjects with active hepatitis B virus infection; or patients with hepatitis C virus infection (defined as positive HCV antibody, and those with HCV-RNA below the detection limit are allowed to enroll); or patients with human immunodeficiency virus infection (defined as positive HIV antibody); or patients with positive treponema pallidum antibody; 14. Having symptoms and signs of epilepsy or chronic intracranial hypertension that are difficult to control with drugs (for example, those using more than 500 ml of mannitol or more than 15 mg of dexamethasone or more than 80 mg of methylprednisolone or other hormones in equivalent doses per day); 15. Subjects judged by the investigator to have severe neurocognitive disorders; 16. Pregnant or lactating women; 17. Those who are considered by the investigator to be unsuitable for participating in this clinical study due to any clinical or laboratory examination abnormalities or other reasons. \-
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Adverse Events (AE) and Serious Adverse Events (SAE) | through study completion, an average of 1 year |
| Dose Limiting Toxicity (DLT) | 28 days |
| Immune effector cell-associated neurotoxicity syndrome (ICANs) | through study completion, an average of 1 year |
| GvHD | through study completion, an average of 1 year |
| CRS | through study completion, an average of 1 year |
Countries
China
Contacts
Primary ContactGuangyuan Hu
Outcome results
None listed