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Immunogene-modified T (IgT) Cells Against Glioblastoma Multiforme

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03170141
Recruitment Status : Enrolling by invitation
First Posted : May 30, 2017
Last Update Posted : January 17, 2023
Sponsor:
Information provided by (Responsible Party):
Lung-Ji Chang, Shenzhen Geno-Immune Medical Institute

Study Description
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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.

Condition or disease Intervention/treatment Phase
Glioblastoma Multiforme of Brain Glioblastoma Multiforme Biological: Antigen-specific IgT cells Phase 1

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.

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: Patients with GBM will be treated with tumor targeting IgT cells expressing immune modulatory genes
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Immunogene-modified Antigen-specific T (IgT) Cells for the Treatment of Glioblastoma Multiforme
Actual Study Start Date : May 31, 2020
Actual Primary Completion Date : August 1, 2020
Estimated Study Completion Date : December 31, 2023

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: Antigen-specific IgT cells
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
 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


Outcome Measures
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Primary Outcome Measures :
  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. [ Time Frame: 2 years ]
    incidents of treatment related adverse events as assessed by CTCAE V4.0.


Secondary Outcome Measures :
  1. Treatment response rate of recurrent glioblastoma [ Time Frame: 6 months ]
    Defined as the proportion of patients who achieved complete remission (CR), partial remission (PR), stable disease (SD), or progressive disease (PD).

  2. Overall survival Rate [ Time Frame: 2 years ]
    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)

  3. Progression-free survival rate [ Time Frame: 2 years ]
    Progression-free Survival (PFS) as determined by the investigator based on RECIST v1.1

  4. Persistence and proliferation of IgT cells in patients [ Time Frame: 2 years ]
    IgT cell percentage in the peripheral blood by flow cytometry or qPCR

  5. Production of specific immune check point modulatory proteins [ Time Frame: 2 years ]
    Specific immune modulators in peripheral blood will be measured by ELISA


Eligibility Criteria
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Ages Eligible for Study:   1 Year to 80 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03170141


Locations
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China, Guangdong
Shenzhen Geno-immune Medical Institute
Shenzhen, Guangdong, China, 518000
Shenzhen People's Hospital
Shenzhen, Guangdong, China, 518100
Sponsors and Collaborators
Shenzhen Geno-Immune Medical Institute
Investigators
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Principal Investigator: Lung-Ji Chang, PhD Shenzhen Geno-Immune Medical Institute
More Information
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Responsible Party: Lung-Ji Chang, President, Shenzhen Geno-Immune Medical Institute
ClinicalTrials.gov Identifier: NCT03170141    
Other Study ID Numbers: GIMI-IRB-17003
First Posted: May 30, 2017    Key Record Dates
Last Update Posted: January 17, 2023
Last Verified: January 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Lung-Ji Chang, Shenzhen Geno-Immune Medical Institute:
CAR T
Gene Therapy
GBM
PD-L1
PD1
Additional relevant MeSH terms:
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Glioblastoma
Astrocytoma
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
 Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue