Study of Neoantigen-specific Adoptive T Cell Therapy for Newly Diagnosed MGMT Negative Glioblastoma Multiforme (GBM)

NCT ID: NCT05685004

Last Updated: 2025-07-01

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE2/PHASE3

Total Enrollment

120 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-09-15

Study Completion Date

2027-03-31

Brief Summary

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This randomized study is designed to compare the combination of TVI-Brain-1 immunotherapy and standard therapy compared to standard therapy alone as a treatment for newly diagnosed MGMT unmethylated glioblastoma patients. The patients' own cancer cells collected after surgery are combined into a vaccine to produce an immune response that significantly increases the number of cancer neoantigen-specific effector T cell precursors in the patient's body. These cancer neoantigen-specific T cells are harvested from the blood, subsequently stimulated and expanded, and infused back into the patient.

Detailed Description

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This randomized study is designed to compare the combination of TVI-Brain-1 immunotherapy and standard therapy compared to standard therapy alone as a treatment for newly diagnosed MGMT unmethylated glioblastoma patients. The general procedures include the collection and testing of cancer tissue samples after surgery and chemoradiation therapy (radiation and temozolomide). For the patients randomized into the investigational study treatment group, they will also receive two vaccinations created from their own cancer cells, undergo leukapheresis to collect immune T-cells from their blood, and transfer of those activated effector T-cells after chemoradiation therapy. All patients are followed with MRIs at follow-up visits.

Conditions

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Glioblastoma Multiforme of Brain

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Outcome Assessors
Blinded over-read of sequential MRI assessments

Study Groups

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Standard of Care

Subjects will have standard surgery which will be followed approximately 5 weeks later by combined radiotherapy and chemotherapy consisting of temozolomide 75 mg/m2 dosed once daily beginning on the first day of radiotherapy and continuing until the final day of radiotherapy. Subjects will receive adjuvant temozolomide, and proceed with post therapy surveillance.

Group Type ACTIVE_COMPARATOR

Standard of Care

Intervention Type PROCEDURE

Surgery for tumor removal or debulking to minimize tumor burden

Radiotherapy

Intervention Type RADIATION

Conformal radiotherapy consists of fractionated focal irradiation at a dose of 2 Gy per fraction given once daily five days per week (Monday through Friday) over a period of six weeks.

Temozolomide

Intervention Type DRUG

All Subjects receive 75 mg/m2 of temozolomide daily beginning on the first day of radiotherapy and continuing until the completion of radiotherapy. Standard of care Subjects will also receive adjuvant temozolomide .

Interventional TVI-Brain-1 Autologous Vaccine and activated autologous blood-derived t cells

TVI-Brain-1 immunotherapy is integrated with radiation and temozolomide in the test group in the following manner: 1) Subjects undergo surgical resection of their cancer and are tapered off steroids. 2) Subjects receive the first vaccination of TVI-Brain-1 as soon as the laboratory prepared vaccine is available for use (approximately 7 - 14 days following surgery). 3) Subjects receive a second vaccination 7-10 days later. 4) Subjects are leukapheresed to obtain immune T cells for ex vivo-activation. 5) Subjects' T cells are stored frozen until after chemoradiotherapy is completed. 6) Following chemoradiotherapy Subjects are infused with activated effector T cells followed by a 10-day course of low-dose interleukin 2 (IL-2). 7) Subjects then proceed with post therapy surveillance.

Group Type EXPERIMENTAL

TVI-Brain-1

Intervention Type BIOLOGICAL

Attenuated autologous cancer cells and activated autologous blood-derived t cells

Standard of Care

Intervention Type PROCEDURE

Surgery for tumor removal or debulking to minimize tumor burden

Radiotherapy

Intervention Type RADIATION

Conformal radiotherapy consists of fractionated focal irradiation at a dose of 2 Gy per fraction given once daily five days per week (Monday through Friday) over a period of six weeks.

Temozolomide

Intervention Type DRUG

All Subjects receive 75 mg/m2 of temozolomide daily beginning on the first day of radiotherapy and continuing until the completion of radiotherapy. Standard of care Subjects will also receive adjuvant temozolomide .

Interventions

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TVI-Brain-1

Attenuated autologous cancer cells and activated autologous blood-derived t cells

Intervention Type BIOLOGICAL

Standard of Care

Surgery for tumor removal or debulking to minimize tumor burden

Intervention Type PROCEDURE

Radiotherapy

Conformal radiotherapy consists of fractionated focal irradiation at a dose of 2 Gy per fraction given once daily five days per week (Monday through Friday) over a period of six weeks.

Intervention Type RADIATION

Temozolomide

All Subjects receive 75 mg/m2 of temozolomide daily beginning on the first day of radiotherapy and continuing until the completion of radiotherapy. Standard of care Subjects will also receive adjuvant temozolomide .

Intervention Type DRUG

Other Intervention Names

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Chemotherapy

Eligibility Criteria

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Inclusion Criteria

* Newly diagnosed MGMT unmethylated glioblastoma multiforme (no prior treatment)
* Sufficient cancer tissue obtained to allow for manufacture of autologous cancer cell vaccines
* The attenuated autologous cancer cell product generated has satisfied the product release criteria as determined by the sponsor quality control department
* Medical history, physical examination and laboratory testing performed within approximately 7 days before enrollment revealing kidney and liver organ function within normal limits
* not currently receiving glucocorticoids and have been off glucocorticoids for at least 24 hours prior to vaccination as well as when they receive the T cell infusion.
* Patient function assessment (Karnofsky score is \> 60)
* a life expectancy of \> 12 weeks.
* Hemoglobin is \> 10 g/dL (may be transfused)
* White blood cell count is \> 3,000 cells/microliter (mcL) of blood.
* Platelet count is \> 100,000 platelets per mcL of blood (transfusion independent)
* Lymphocyte count is \> 1,000 cells/mcL of blood.

Exclusion Criteria

* another concomitant life-threatening disease (not including glioblastoma multiforme)
* a second malignancy that is not in remission as determined by the clinical investigator. Exception: squamous or basal cell carcinoma of the skin.
* requirement for treatment with glucocorticoids to control brain swelling
* presence of active autoimmune disease that is currently being actively treated.
* psychological, familial, sociological or geographical conditions that do not permit adequate medical follow-up and compliance with the study protocol.
* Current pregnancy or a plan to become pregnant within 1-year following the study.
Minimum Eligible Age

18 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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TVAX Biomedical

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Jean Aguiar, APRN

Role: STUDY_DIRECTOR

TVAX Biomedical, Inc

Locations

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Center for Neurosciences

Tucson, Arizona, United States

Site Status

Cedar-Sanai Medical Center

Los Angeles, California, United States

Site Status

University of Southern California Keck School of Medicine

Los Angeles, California, United States

Site Status

Moffitt Cancer Center

Tampa, Florida, United States

Site Status

Aaron Mammoser

Atlanta, Georgia, United States

Site Status

University of Kansas Medical Center

Kansas City, Kansas, United States

Site Status

Capital Health

Pennington, New Jersey, United States

Site Status

Providence St. Vincent

Portland, Oregon, United States

Site Status

Countries

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United States

References

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Holladay FP, Heitz T, Chen YL, Chiga M, Wood GW. Successful treatment of a malignant rat glioma with cytotoxic T lymphocytes. Neurosurgery. 1992 Sep;31(3):528-33. doi: 10.1227/00006123-199209000-00015.

Reference Type BACKGROUND
PMID: 1407433 (View on PubMed)

Holladay FP, Heitz T, Wood GW. Antitumor activity against established intracerebral gliomas exhibited by cytotoxic T lymphocytes, but not by lymphokine-activated killer cells. J Neurosurg. 1992 Nov;77(5):757-62. doi: 10.3171/jns.1992.77.5.0757.

Reference Type BACKGROUND
PMID: 1403119 (View on PubMed)

Plautz GE, Touhalisky JE, Shu S. Treatment of murine gliomas by adoptive transfer of ex vivo activated tumor-draining lymph node cells. Cell Immunol. 1997 Jun 15;178(2):101-7. doi: 10.1006/cimm.1997.1140.

Reference Type BACKGROUND
PMID: 9225000 (View on PubMed)

Sloan AE, Dansey R, Zamorano L, Barger G, Hamm C, Diaz F, Baynes R, Wood G. Adoptive immunotherapy in patients with recurrent malignant glioma: preliminary results of using autologous whole-tumor vaccine plus granulocyte-macrophage colony-stimulating factor and adoptive transfer of anti-CD3-activated lymphocytes. Neurosurg Focus. 2000 Dec 15;9(6):e9. doi: 10.3171/foc.2000.9.6.10.

Reference Type BACKGROUND
PMID: 16817692 (View on PubMed)

Wood GW, Turner T, Wang YY, Holladay FP. Immune rejection of intracerebral gliomas using lymphocytes from glioma-bearing rats. J Immunother. 1999 Nov;22(6):497-505. doi: 10.1097/00002371-199911000-00004.

Reference Type BACKGROUND
PMID: 10570748 (View on PubMed)

Provided Documents

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Document Type: Informed Consent Form

View Document

Other Identifiers

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TVI-AST-008

Identifier Type: -

Identifier Source: org_study_id

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