Immunogene-modified T (IgT) Cells Against Glioblastoma Multiforme

Glioblastoma Multiforme Clinical Trial

Official title:

Immunogene-modified Antigen-specific T (IgT) Cells for the Treatment of Glioblastoma Multiforme

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT03170141
• Other study ID #: GIMI-IRB-17003
• Status: Enrolling by invitation
• Phase: Phase 1
• Start date: May 31, 2020
• Est. completion date: December 31, 2023

Study information

• Verified date: January 2023
• Source: Shenzhen Geno-Immune Medical Institute
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study aims to treat patients who have been diagnosed with brain cancer including glioblastoma multiforme (GBM). 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 antigen-specific T cells. Thus, in this study, the gene-modified T cells specific for GBM antigens will be combined with immune modulatory genes to treat patients in dose escalation cohorts.

Description:

Background:

Glioblastoma multiforme (GBM) is the most dangerous and aggressive form of brain cancer. Chimeric antigen receptor (CAR)-modified T cells have been shown to mediate long-term durable remissions in recurrent or refractory CD19+ B cell malignancies, and thus the CAR-T therapy approach is considered a promising treatment against GBM. Certain antigens are highly specific in GBM, such as epidermal growth factor receptor variant iii, EGFRviii. EGFRviii is a variant form of EGFR protein, and one of the potential target antigens in GBM. Alternative antigens such as GD2 and MucI have also been targeted as potential GBM antigens.

Tumor microenvironment is known to suppressive anti-cancer immune responses. Many immune checkpoint inhibitors have demonstrated marked anti-tumor activities. Instead of infusing antibodies, this study aims to infuse antigen-specific T cells modified with immune modulatory genes (IgT) such as genes encoding immune checkpoint inhibitors. Combination of tumor targeting and immune modulatory activities, the IgT cells could target both the tumor cells and the tumor microenvironment.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 20
• Est. completion date: December 31, 2023
• Est. primary completion date: August 1, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Year to 80 Years

Eligibility

Inclusion Criteria:

1. abilities to understand and the willingness to provide written informed consent;

2. patients are = 1 and = 80 years old;

3. 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;

4. Malignant cells are target antigen positive confirmed by immunostaining, quantitative PCR or sequencing;

5. karnofsky performance score (KPS) = 60;

6. life expectancy >3 months;

7. 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;

8. peripheral blood absolute lymphocyte count must be above 0.8×10^9/L;

9. satisfactory heart functions;

10. patients must be willing to follow the orders of doctors;

11. 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.

Exclusion Criteria:

1. a prior history of gliadel implantation 4 weeks before this study start or antibody based therapies;

2. HIV positive;

3. tuberculosis infection not under control;

4. history of autoimmune disease, or other diseases require long-term administration of steroids or immunosuppressive therapies;

5. history of allergic disease, or allergy to immune cells or study product excipients;

6. patients already enrolled in other immune cell clinical study;

7. patients, in the opinion of investigators, may not be eligible or not able to comply with the study.

Related Conditions & MeSH terms

• Glioblastoma
• Glioblastoma Multiforme
• Glioblastoma Multiforme of Brain

Intervention

Biological:
• Antigen-specific IgT cells
Tumor antigen-specific IgT cells are infused intravenously or directly to the tumor location of the patients in a three-day split-dose regimen(day 0,10%; day1, 30%; day2, 60%)to complete a total targeted dose. Drug: cyclophosphamide 250 mg/m^2 d1-3; Drug: Fludarabine 25mg/m^2 d1-3

Locations

Country	Name	City	State
China	Shenzhen Geno-immune Medical Institute	Shenzhen	Guangdong
China	Shenzhen People's Hospital	Shenzhen	Guangdong

Sponsors (1)

Lead Sponsor	Collaborator
Shenzhen Geno-Immune Medical Institute

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	2 years
Secondary	Treatment response rate of recurrent glioblastoma	Defined as the proportion of patients who achieved complete remission (CR), partial remission (PR), stable disease (SD), or progressive disease (PD).	6 months
Secondary	Overall survival Rate	Percentage of participants with objective response as determined by the investigator based on Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST v1.1)	2 years
Secondary	Progression-free survival rate	Progression-free Survival (PFS) as determined by the investigator based on RECIST v1.1	2 years
Secondary	Persistence and proliferation of IgT cells in patients	IgT cell percentage in the peripheral blood by flow cytometry or qPCR	2 years
Secondary	Production of specific immune check point modulatory proteins	Specific immune modulators in peripheral blood will be measured by ELISA	2 years