Glioblastoma (GBM), Glioblastoma Multiforme (GBM)
Conditions
Keywords
Glioblastoma, Glioblastoma Multiforme, Immunotherapy, Gamma Delta T Cell, γδT
Brief summary
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.
Interventions
DRUGAllogeneic γδ T (ABOUT) cells
Allogeneic γδ T cells genetically edited to knockout the ARIH1 and BCL11b genes.
Sponsors
Peking University
Changping Laboratory
Peking University Third Hospital
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
3+3 Dose escalation design
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
1. Male or female, age 18-70 years old (both ends included) 2. 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 3. Karnofsky Performance Status (KPS) ≥ 60% 4. Life expectancy \> 4 weeks 5. 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) 6. Must be able to undergo an MRI with contrast 7. Must have adequate organ and marrow function as defined below: * White blood cell count (WBC) ≥ 3 x 10\^9/L * Absolute neutrophil count (ANC) \> 1 x 10\^9/L * Hemoglobin (Hb) ≥ 90 g/L * Platelet (PLT) ≥ 80×10\^9/L * Albumin transaminase (ALT) & albumin transaminase (AST) \< 1.5 × institutional upper limit of normal (ULN) * Serum creatinine (Cr) \< 1.5 x institutional ULN * Total bilirubin \< 1.5 x institutional ULN * PT & PTT ≤ 1.25 x institutional ULN 8. No obvious hereditary diseases 9. Normal cardiac function with left ventricular ejection fraction \>55% 10. No bleeding and coagulation disorders 11. 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 12. 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 13. Signed, written informed consent
Exclusion criteria
1. Active hepatitis B or C virus, HIV infection, or other untreated active infection 2. Pregnant and lactating women 3. Participants with organ failure 4. Participants with a chronic disease requiring immunologic or hormonal therapy 5. Participants with an allergy to immunotherapy and related cells 6. Participants with uncontrolled intercurrent illness 7. Participants with psychiatric illness/social situations that would limit compliance with study requirements 8. Participants with a history of organ transplantation or who are awaiting organ transplantation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Adverse Events (AEs) | 3 months following ABOUT γδT cells administration | 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. |
| Incidence of Dose-Limiting Toxicities (DLTs) | 28 days following initial treatment with ABOUT γδT cells | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) | 3 months following ABOUT γδT cells administration | According to modified RANO criteria, ORR is defined as proportion of subjects with confirmed CR and PR. |
| Duration of response (DOR) | 3 months following ABOUT γδT cells administration | 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. |
Countries
China
Contacts
Primary ContactChenlong YANG, M.D., Ph.D.
Outcome results
None listed