Immunogene-modified T (IgT) Cells Against Glioblastoma Multiforme

NCT03170141 | Enrolling By Invitation Phase 1

• 1 other identifier: GIMI-IRB-17003
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

This study aims to treat patients who have been diagnosed with brain cancer glioblastoma multiforme (GBM) including diffuse intrinsic pontine glioma (DIPG) and diffuse midline glioma (DMG). The treatment combines two different approaches to fight cancer: immune modulators and antigen-specific T cells. Immune checkpoint antibodies have been tested on various tumors with good outcomes. GBM is known to express increased levels of certain antigens that can be targeted by T cells including chimeric antigen receptor-modified T (CAR-T) cells and tumor antigen specific cytotoxic lymphocytes (CTLs). In this study, the gene-modified T cells specific for GBM antigens will be combined with immune modulatory gene-modified dendritic cells (DCs) as individualized treatment regimens to treat patients.

Conditions

Glioblastoma Multiforme of Brain; Brain Cancer

Keywords

CAR T; Gene Therapy; GBM; GD2; CD276; PD1

Outcome Measures

Primary Outcomes (1)

• Safety of infusion of autologous IgT cells with cyclophosphamide and fludarabine as lymphodepleting chemotherapy in patients with recurrent glioblastoma using the NCI CTCAE V4.0 criteria.

  incidents of treatment related adverse events as assessed by CTCAE V4.0.

  1 years

Secondary Outcomes (4)

• Treatment response rate of recurrent glioblastoma

  6 months

• Overall survival Rate

  2 years

• Progression-free survival rate

  2 years

• Persistence and proliferation of IgT cells in patients

  2 years

Study Arms (1)

Antigen-specific IgT cells

EXPERIMENTAL

Patients will receive non-myeloablative chemotherapy consisting of fludarabine and cyclophosphamide, followed by intravenous infusion of autologous IgT cells. The tested IgT cell dosage ranges from 5×10\^5 /kg to 5×10\^6 /kg

Biological: Antigen-specific IgT cells

Interventions

Antigen-specific IgT cells BIOLOGICAL

Tumor antigen-specific IgT cells are infused intravenously . Drug: cyclophosphamide 250 mg/m\^2 d1-3; Drug: Fludarabine 25mg/m\^2 d1-3

Antigen-specific IgT cells

Eligibility Criteria

• Age: 6 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• abilities to understand and the willingness to provide written informed consent;
• patients are ≥ 6 and ≤ 70 years old;
• recurrent glioblastoma or brain tumor patients with measurable tumors. Patients have received standard care of medication, such as gross total resection with concurrent radio-chemotherapy (\~54 - 60 Gy, TMZ). Patients must either not be receiving dexamethasone or receiving ≤ 4 mg/day at the time of leukopheresis;
• karnofsky performance score (KPS) ≥ 60;
• life expectancy \>3 months;
• satisfactory bone marrow, liver and kidney functions as defined by the following: absolute neutrophile count ≥ 1500/mm\^3; hemoglobin \> 10 g/dL; platelets \> 100000 /mm\^3; Bilirubin \< 1.5×ULN; alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \< 2.5×ULN; creatinine \< 1.5×ULN;
• peripheral blood absolute lymphocyte count must be above 0.8×10\^9/L;
• satisfactory heart functions;
• patients must be willing to follow the instructions of doctors;
• women of reproductive potential (between 15 and 49 years old) must have a negative pregnancy test within 7 days of study start. Male and female patients of reproductive potential must agree to use birth control during the study and 3 months post study.

You may not qualify if:

• a prior history of gliadel implantation 4 weeks before this study start or currently receiving antibody based therapies;
• HIV positive;
• tuberculosis infection not under control;
• history of autoimmune disease, or other diseases require long-term administration of steroids or immunosuppressive therapies;
• history of allergic disease, or allergy to immune cells or study product excipients;
• patients already enrolled in other immune cell clinical study;
• patients, in the opinion of investigators, may not be eligible or not able to comply with the study.

Sponsors & Collaborators

• Shenzhen Geno-Immune Medical Institute: lead

Study Sites (1)

Shenzhen Geno-immune Medical Institute

Shenzhen, Guangdong, 518000, China

Location

Related Publications (1)

• Liu Z, Zhou J, Yang X, Liu Y, Zou C, Lv W, Chen C, Cheng KK, Chen T, Chang LJ, Wu D, Mao J. Safety and antitumor activity of GD2-Specific 4SCAR-T cells in patients with glioblastoma. Mol Cancer. 2023 Jan 9;22(1):3. doi: 10.1186/s12943-022-01711-9.

  PMID: 36617554 DERIVED

MeSH Terms

Conditions

Brain Neoplasms

Condition Hierarchy (Ancestors)

Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Study Officials

• Lung-Ji Chang, PhD

  Shenzhen Geno-Immune Medical Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: President

Model Details: Patients with GBM will be treated with tumor targeting IgT cells including CAR-T cells

Study Record Dates

• First Submitted: May 25, 2017
• First Posted: May 30, 2017
• Study Start: May 31, 2017
• Primary Completion (Estimated): July 31, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: April 24, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)