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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| MT027 | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| MT027 cells suspension | Drug | MT027: CRISPR/Cas9 edited B7H3-specific allogeneic CAR-T cells |
|
| Measure | Description | 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 |
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Inclusion Criteria:
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.
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Guangyuan Hu | Contact | +86-027-83663405 | h.g.y.121@163.com |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Tongji Hospital affiliated to Tongji Medical College of Huazhong University of Science & Technology | Wuhan | Hubei | 430030 | China |
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| ID | Term |
|---|---|
| D005910 | Glioma |
| ID | Term |
|---|---|
| D018302 | Neoplasms, Neuroepithelial |
| D017599 | Neuroectodermal Tumors |
| D009373 | Neoplasms, Germ Cell and Embryonal |
| D009370 | Neoplasms by Histologic Type |
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| D009369 | Neoplasms |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009380 | Neoplasms, Nerve Tissue |