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Immunogene-modified T (IgT) Cells Against Glioblastoma Multiforme

Primary Purpose

Glioblastoma Multiforme of Brain, Glioblastoma Multiforme

Status

Enrolling by invitation

Phase

Phase 1

Locations

China

Study Type

Interventional

Intervention

Antigen-specific IgT cells

About this trial

This is an interventional treatment trial for Glioblastoma Multiforme of Brain focused on measuring CAR T, Gene Therapy, GBM, PD-L1, PD1

Eligibility Criteria

1 Year - 80 Years (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

abilities to understand and the willingness to provide written informed consent;
patients are ≥ 1 and ≤ 80 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;
Malignant cells are target antigen positive confirmed by immunostaining, quantitative PCR or sequencing;
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 orders 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.

Exclusion Criteria:

a prior history of gliadel implantation 4 weeks before this study start or 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.

Sites / Locations

Shenzhen Geno-immune Medical Institute
Shenzhen People's Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Antigen-specific IgT cells

Arm Description

Patients will receive non-myeloablative chemotherapy consisting of fludarabine and/or cyclophosphamide, followed by intravenous infusion of autologous IgT cells. A standard 3+3 escalation approach will be used to obtain the safe dosage of IgT cells. The tested IgT cell dosage ranges from 0.5×10^5 /kg to 2.5×10^7 /kg

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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).

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)

Progression-free survival rate

Progression-free Survival (PFS) as determined by the investigator based on RECIST v1.1

Persistence and proliferation of IgT cells in patients

IgT cell percentage in the peripheral blood by flow cytometry or qPCR

Production of specific immune check point modulatory proteins

Specific immune modulators in peripheral blood will be measured by ELISA

Full Information

NCT ID

NCT03170141

First Posted

May 25, 2017

Last Updated

January 13, 2023

Sponsor

Shenzhen Geno-Immune Medical Institute

1. Study Identification

Unique Protocol Identification Number

NCT03170141

Brief Title

Immunogene-modified T (IgT) Cells Against Glioblastoma Multiforme

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

January 2023

Overall Recruitment Status

Enrolling by invitation

Study Start Date

May 31, 2020 (Actual)

Primary Completion Date

August 1, 2020 (Actual)

Study Completion Date

December 31, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Shenzhen Geno-Immune Medical Institute

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief 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.

Detailed 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Glioblastoma Multiforme of Brain, Glioblastoma Multiforme

Keywords

CAR T, Gene Therapy, GBM, PD-L1, PD1

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Model Description

Patients with GBM will be treated with tumor targeting IgT cells expressing immune modulatory genes

Masking

None (Open Label)

Allocation

N/A

Enrollment

20 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Antigen-specific IgT cells

Arm Type

Experimental

Arm Description

Intervention Type

Biological

Intervention Name(s)

Antigen-specific IgT cells

Intervention Description

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

Primary Outcome Measure Information:

Title

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.

Description

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

Time Frame

2 years

Secondary Outcome Measure Information:

Title

Treatment response rate of recurrent glioblastoma

Description

Defined as the proportion of patients who achieved complete remission (CR), partial remission (PR), stable disease (SD), or progressive disease (PD).

Time Frame

6 months

Title

Overall survival Rate

Description

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)

Time Frame

2 years

Title

Progression-free survival rate

Description

Progression-free Survival (PFS) as determined by the investigator based on RECIST v1.1

Time Frame

2 years

Title

Persistence and proliferation of IgT cells in patients

Description

IgT cell percentage in the peripheral blood by flow cytometry or qPCR

Time Frame

2 years

Title

Production of specific immune check point modulatory proteins

Description

Specific immune modulators in peripheral blood will be measured by ELISA

Time Frame

2 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

1 Year

Maximum Age & Unit of Time

80 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: abilities to understand and the willingness to provide written informed consent; patients are ≥ 1 and ≤ 80 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; Malignant cells are target antigen positive confirmed by immunostaining, quantitative PCR or sequencing; 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 orders 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. Exclusion Criteria: a prior history of gliadel implantation 4 weeks before this study start or 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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Lung-Ji Chang, PhD

Organizational Affiliation

Shenzhen Geno-Immune Medical Institute

Official's Role

Principal Investigator

Facility Information:

Facility Name

Shenzhen Geno-immune Medical Institute

City

Shenzhen

State/Province

Guangdong

ZIP/Postal Code

518000

Country

China

Facility Name

Shenzhen People's Hospital

City

Shenzhen

State/Province

Guangdong

ZIP/Postal Code

518100

Country

China

12. IPD Sharing Statement

Plan to Share IPD

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Immunogene-modified T (IgT) Cells Against Glioblastoma Multiforme

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