Allogeneic γδT Cells in Glioblastoma

NCT07144735 | Recruiting DMC

• 1 other identifier: M20250397
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 3

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.

Conditions

Glioblastoma (GBM); Glioblastoma Multiforme (GBM)

Keywords

Glioblastoma; Glioblastoma Multiforme; Immunotherapy; Gamma Delta T Cell; γδT

Outcome Measures

Primary Outcomes (2)

• 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

Secondary Outcomes (2)

• Objective Response Rate (ORR)

  3 months following ABOUT γδT cells administration

• Duration of response (DOR)

  3 months following ABOUT γδT cells administration

Study Arms (3)

Low dose

EXPERIMENTAL

Dose 1: 7x10\^7 ABOUT γδT, local administration every 3-4 weeks

Drug: Allogeneic γδ T (ABOUT) cells

Medium dose

EXPERIMENTAL

Dose 2: 1.1x10\^8 ABOUT γδT, local administration every 3-4 weeks

Drug: Allogeneic γδ T (ABOUT) cells

High dose

EXPERIMENTAL

Dose 3: 1.6x10\^8 ABOUT γδT, local administration every 3-4 weeks

Drug: Allogeneic γδ T (ABOUT) cells

Interventions

Allogeneic γδ T (ABOUT) cells DRUG

Allogeneic γδ T cells genetically edited to knockout the ARIH1 and BCL11b genes.

Also known as: ARIH1 and BCL11b knockout γδ T cells, ARIH1KO/BCL11bKO γδ T cells

High dose; Low dose; Medium dose

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• 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

You may not qualify if:

• Active hepatitis B or C virus, HIV infection, or other untreated active infection
• Pregnant and lactating women
• Participants with organ failure
• Participants with a chronic disease requiring immunologic or hormonal therapy
• Participants with an allergy to immunotherapy and related cells
• Participants with uncontrolled intercurrent illness
• Participants with psychiatric illness/social situations that would limit compliance with study requirements
• Participants with a history of organ transplantation or who are awaiting organ transplantation

Sponsors & Collaborators

• Peking University Third Hospital: lead
• Peking University: collaborator
• Changping Laboratory: collaborator

Study Sites (3)

Peking University Third Hospital

Beijing, Beijing Municipality, 100191, China

RECRUITING

Zhengzhou Second Hospital

Zhengzhou, Henan, 450052, China

RECRUITING

Henan Academy of Innovations in Medical Science

Zhengzhou, Henan, 451162, China

RECRUITING

MeSH Terms

Conditions

Glioblastoma

Interventions

Cell Count

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Cell Physiological Phenomena

Central Study Contacts

Chenlong YANG, M.D., Ph.D.

CONTACT

(+86)-135-1108-7060; vik.yang@pku.edu.cn

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Research Professor

Model Details: 3+3 Dose escalation design

Study Record Dates

• First Submitted: August 14, 2025
• First Posted: August 27, 2025
• Study Start: April 1, 2025
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2030
• Last Updated: August 27, 2025

Record last verified: 2025-08

Locations

CN (3)