Immunogene-modified T (IgT) Cells Against Glioblastoma Multiforme
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ClinicalTrials.gov Identifier: NCT03170141 |
Recruitment Status :
Enrolling by invitation
First Posted : May 30, 2017
Last Update Posted : January 17, 2023
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Tracking Information | |||||
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First Submitted Date ICMJE | May 25, 2017 | ||||
First Posted Date ICMJE | May 30, 2017 | ||||
Last Update Posted Date | January 17, 2023 | ||||
Actual Study Start Date ICMJE | May 31, 2020 | ||||
Actual Primary Completion Date | August 1, 2020 (Final data collection date for primary outcome measure) | ||||
Current Primary Outcome Measures ICMJE |
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.
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Original Primary Outcome Measures ICMJE |
Safety of infusion of autologous anti-EGFRvIII CAR T 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.
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Change History | |||||
Current Secondary Outcome Measures ICMJE |
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Original Secondary Outcome Measures ICMJE |
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Current Other Pre-specified Outcome Measures | Not Provided | ||||
Original Other Pre-specified Outcome Measures | Not Provided | ||||
Descriptive Information | |||||
Brief Title ICMJE | Immunogene-modified T (IgT) Cells Against Glioblastoma Multiforme | ||||
Official Title ICMJE | Immunogene-modified Antigen-specific T (IgT) Cells for the Treatment of Glioblastoma Multiforme | ||||
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. |
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Study Type ICMJE | Interventional | ||||
Study Phase ICMJE | Phase 1 | ||||
Study Design ICMJE | 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 |
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Condition ICMJE |
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Intervention ICMJE | 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
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Study Arms ICMJE | 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
Intervention: Biological: Antigen-specific IgT cells
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Publications * | Not Provided | ||||
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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Recruitment Information | |||||
Recruitment Status ICMJE | Enrolling by invitation | ||||
Estimated Enrollment ICMJE |
20 | ||||
Original Estimated Enrollment ICMJE | Same as current | ||||
Estimated Study Completion Date ICMJE | December 31, 2023 | ||||
Actual Primary Completion Date | August 1, 2020 (Final data collection date for primary outcome measure) | ||||
Eligibility Criteria ICMJE | Inclusion Criteria:
Exclusion Criteria:
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Sex/Gender ICMJE |
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Ages ICMJE | 1 Year to 80 Years (Child, Adult, Older Adult) | ||||
Accepts Healthy Volunteers ICMJE | No | ||||
Contacts ICMJE | Contact information is only displayed when the study is recruiting subjects | ||||
Listed Location Countries ICMJE | China | ||||
Removed Location Countries | |||||
Administrative Information | |||||
NCT Number ICMJE | NCT03170141 | ||||
Other Study ID Numbers ICMJE | GIMI-IRB-17003 | ||||
Has Data Monitoring Committee | No | ||||
U.S. FDA-regulated Product |
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IPD Sharing Statement ICMJE |
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Current Responsible Party | Lung-Ji Chang, Shenzhen Geno-Immune Medical Institute | ||||
Original Responsible Party | Same as current | ||||
Current Study Sponsor ICMJE | Shenzhen Geno-Immune Medical Institute | ||||
Original Study Sponsor ICMJE | Same as current | ||||
Collaborators ICMJE | Not Provided | ||||
Investigators ICMJE |
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PRS Account | Shenzhen Geno-Immune Medical Institute | ||||
Verification Date | January 2023 | ||||
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |