Recurrent Glioblastoma Multiforme (GBM)
Conditions
Keywords
GBM
Brief summary
A phase I study to evaluate the safety, tolerance and pharmacokinetics of SNC109 in patients with rGBM
Detailed description
It is planned to recruit about 50 patients with rGBM subjects. The protocol consists of screening period, Lymphocytes apheresis period, Operation period, pre-infusion evaluation (-2\ -1 days), infusion (day 0), infusion observation (day 1-post infusion), and follow-up period (last infusion-720 days). The incidence of dose limitation toxicity (DLT) will be observed within 28 days after the first infusion. Subjects in this study will receive multiple infusions, starting with 5×104 CAR+ T cells/dose in the first subject, and the Safety Review Committee (SRC) will evaluate the subsequent dosing regimen, dose, infusion interval, and number of treatment cycles. Subsequent subjects will be evaluated by the SRC on the basis of available PK and safety data, and the SRC will determine the dosing regimen, dose, infusion interval and number of treatment cycles based on observed evidences.
Interventions
DRUGSNC109
SNC-109 CAR-T Cells, first dose from 5×104 CAR+ T Cells, treatment follows the operation and the next dose would be deiced by SRC
Sponsors
Shanghai Simnova Biotechnology Co.,Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age ≥18，both sexes; * Diagnosed with a history of glioblastoma, and the recurrent glioblastoma has confirmed by histological/molecular pathology (including astrocytoma World Health Organization (WHO) Grade 4); * Karnofsky (KPS) ≥50; * The estimated survival time is ≥12 weeks; * Blood pregnancy tests for women of childbearing age are negative; * The patient himself/herself, and/or his/her legal guardian, agree to participate in the trial and sign the informed consent form.
Exclusion criteria
* Known allergies to study drugs or drugs that may be used in the study; * Severe concurrent diseases in the heart, lungs, liver, or other vital organs; * Hypertension is poorly controlled or accompanied by hypertensive crisis or hypertensive encephalopathy; * In addition to the glioblastoma, with other severe central nervous system diseases or complications or aggressive malignancies; * Long-term use of immunosuppressant drugs, or large doses of steroids; * Received live or attenuated vaccine or other surgery had no related to GBM within 4 weeks prior to Lymphocytes apheresis; * Lymphocytes apheresis or cell infusion combined with infection or unexplained fever.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of treatment related adverse events | Up to 28 days after first infusion | Incidence of adverse events associated with CAR-T cell transfusion within 28 days of the first infusion, abnormal and clinical significant laboratory results |
| DLT | Up to 28 days after first infusion | Incidence of DLT associated with CAR-T cell transfusion within 28 days of the first infusion |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetic (PK) profile/parameters Peak Plasma Concentration (Cmax) of SNC-109 Cell count and CAR vector copy number | within 2 years after first infusion | Peak Plasma Concentration (Cmax) |
| Pharmacokinetic (PK) profile/parameters Area under the plasma concentration versus time curve (AUC) | within 2 years after first infusion | Area under the plasma concentration versus time curve (AUC) of SNC-109 Cell count |
| Progression free survival (PFS) after infusion | within 2 years after first infusion | The data of Overall survival (OS) after infusion |
| Overall survival (OS) after infusion | within 2 years after first infusion | The data of Overall survival (OS) after infusion |
| Pharmacodynamic (PD) profile/parameters Changes of Cytokines after infusion | within 2 years after first infusion | Changes of cytokines (such as Interleukin-6, Interleukin-8 etc.) in peripheral blood (PB) and cerebrospinal fluid (CSF) pre-and post- infusion and at each of the main follow-up time points, and the time to recovery |
| Concentration of Human anti-chimeric antibody (HACA) | within 2 years after first infusion | Detection of changes in peripheral blood and cerebrospinal fluid Human anti-chimeric antibody (HACA) |
| Efficacy assesment for the treatment according to iRANO | within 2 years after first infusion | Assessment of disease response rates according to the Immunological Response Assessment in Neuro-Oncology (iRANO) |
| Time maximum of SNC-109 Cell count and CAR vector copy number | within 2 years after first infusion | Pharmacokinetic (PK) profile/parameter Tmax |
Countries
China
Outcome results
None listed