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| Name | Class |
|---|---|
| Peking University | OTHER |
| Changping Laboratory | OTHER |
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This first-in-human clinical study aims to evaluate the safety and feasibility of locally delivered, allogeneic γδ T cells (genetically edited with ARIH1 and BCL11b knockout, designated ABOUT γδT cells) in patients with glioblastoma multiforme (GBM). The engineered effector cells are delivered via localized administration to selectively target and eliminate residual GBM cells. ABOUT: ARIH1 and BCL11b knockOUT γδ T cells.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Low dose | Experimental | Dose 1: 7x10^7 ABOUT γδT, local administration every 3-4 weeks |
|
| Medium dose | Experimental | Dose 2: 1.1x10^8 ABOUT γδT, local administration every 3-4 weeks |
|
| High dose | Experimental | Dose 3: 1.6x10^8 ABOUT γδT, local administration every 3-4 weeks |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Allogeneic γδ T (ABOUT) cells | Drug | Allogeneic γδ T cells genetically edited to knockout the ARIH1 and BCL11b genes. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Incidence of Adverse Events (AEs) | Defined as the incidence of ≥ Grade 3-4 adverse events related to ABOUT γδT cells according to common terminology criteria for adverse events (CTCAE) v6.0. | 3 months following ABOUT γδT cells administration |
| Incidence of Dose-Limiting Toxicities (DLTs) | Defined as events attributable to ABOUT γδT cells infusion within 28 days post-infusion. Grade 3-4 acute graft-versus-host disease (GvHD) according to the Mount Sinai Acute GvHD International Consortium criteria; Grade 3 or higher cytokine release syndrome (CRS) lasting more than 2 weeks, according to American Society for Transplantation and Cellular Therapy (ASTCT) criteria; Any ABOUT γδT cells-related AE requiring intubation; Grade 4 non-hematologic toxicities. | 28 days following initial treatment with ABOUT γδT cells |
| Measure | Description | Time Frame |
|---|---|---|
| Objective Response Rate (ORR) | According to modified RANO criteria, ORR is defined as proportion of subjects with confirmed CR and PR. | 3 months following ABOUT γδT cells administration |
| Duration of response (DOR) |
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Inclusion Criteria:
Male or female, age 18-70 years old (both ends included)
At least one evaluable lesion with previous biopsy or pathohistologic confirmation of glioblastoma (WHO grade IV), with imaging suggestive of continued progression or recurrence after comprehensive treatment
Karnofsky Performance Status (KPS) ≥ 60%
Life expectancy > 4 weeks
Patients who completed radiotherapy or systemic therapies (including temozolomide/bevacizumab or other agents) for at least 4 weeks prior to enrollment. All prior treatment-related toxicities should be defined as ≤ grade 1 (except for toxicities such as alopecia or leukoplakia) according to the Common Terminology Standard for Adverse Events (CTCAE 6.0)
Must be able to undergo an MRI with contrast
Must have adequate organ and marrow function as defined below:
No obvious hereditary diseases
Normal cardiac function with left ventricular ejection fraction >55%
No bleeding and coagulation disorders
Absence of positive blood cultures for bacteria, fungus, or virus within 48-hours prior to ABOUT γδT cell infusion and/or there aren't any indications of meningitis
Fertile women must have had a pregnancy test with a negative result within 7 days prior to the start of treatment, and subjects are willing to use contraception (hormonal or barrier method of birth control or abstinence) during the clinical trial and for 6 months after the last cell infusion; should a woman become pregnant or suspect that she is pregnant while participating on the trial, she should inform her treating physician immediately
Signed, written informed consent
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Chenlong YANG, M.D., Ph.D. | Contact | (+86)-135-1108-7060 | vik.yang@pku.edu.cn |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Peking University Third Hospital | Recruiting | Beijing | Beijing Municipality | 100191 | China |
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| ID | Term |
|---|---|
| D005909 | Glioblastoma |
| ID | Term |
|---|---|
| D001254 | Astrocytoma |
| D005910 | Glioma |
| D018302 | Neoplasms, Neuroepithelial |
| D017599 | Neuroectodermal Tumors |
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| ID | Term |
|---|---|
| D002452 | Cell Count |
| ID | Term |
|---|---|
| D003584 | Cytological Techniques |
| D019411 | Clinical Laboratory Techniques |
| D019937 | Diagnostic Techniques and Procedures |
| D003933 | Diagnosis |
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3+3 Dose escalation design
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According to modified RANO criteria, DOR is defined as time from the date when a response of confirmed CR/PR is first met to the date of confirmed disease progression or death.
| 3 months following ABOUT γδT cells administration |
| Zhengzhou Second Hospital | Recruiting | Zhengzhou | Henan | 450052 | China |
|
| Henan Academy of Innovations in Medical Science | Recruiting | Zhengzhou | Henan | 451162 | China |
|
| D009373 |
| Neoplasms, Germ Cell and Embryonal |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009380 | Neoplasms, Nerve Tissue |
| D008919 | Investigative Techniques |
| D002468 | Cell Physiological Phenomena |