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

Glioblastoma Multiforme of Brain Clinical Trial

Official title:

Randomized Phase 2b Study of Safety And Efficacy Of TVI-Brain-1 Combined With Conformal Radiotherapy And Temozolomide Vs Standard Therapy In Newly Diagnosed MGMT Negative Glioblastoma Multiforme (GBM)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05685004
• Other study ID #: TVI-AST-008
• Status: Recruiting
• Phase: Phase 2/Phase 3
• Start date: September 15, 2023
• Est. completion date: March 2026

Study information

• Verified date: April 2024
• Source: TVAX Biomedical
• Contact: Jean Aguiar
• Phone: 1 913 492 2221
• Email: info[@]tvaxbiomedical.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 96
• Est. completion date: March 2026
• Est. primary completion date: December 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Glioblastoma
• Glioblastoma Multiforme of Brain

Intervention

Biological:
• TVI-Brain-1
Attenuated autologous cancer cells and activated autologous blood-derived t cells

Procedure:
• Standard of Care
Surgery for tumor removal or debulking to minimize tumor burden

Radiation:
• 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.

Drug:
• 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 .

Locations

Country	Name	City	State
United States	University of Kansas Medical Center	Kansas City	Kansas
United States	Cedar-Sanai Medical Center	Los Angeles	California
United States	University of Southern California Keck School of Medicine	Los Angeles	California
United States	Capital Health	Newark	New Jersey
United States	Advent Health	Orlando	Florida

Sponsors (1)

Lead Sponsor	Collaborator
TVAX Biomedical

Country where clinical trial is conducted

United States, 

References & Publications (5)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Number of participants with treatment-related adverse events as assessed by CTCAE v4.0	Assessment of changes in patient through Physical Examination	Through study completion, an average of 2 years
Other	Immunogenicity	Delayed-type hypersensitivity (DTH) skin testing using attenuated autologous cancer cells will be performed to assess the immunogenicity of the Subject's cancer.	Assessed at 24 hours after each vaccine administration
Other	Other genetic and immunologic parameters	The study is also designed to determine whether a wide variety of genetic and immunologic parameters that are monitored during and following treatment correlate with clinical outcomes	Assessed at 24 hours after each vaccine administration
Primary	Survival	All Subjects will be evaluated and contacted to evaluate their status	From date of randomization until the date of death from any cause assessed up to 24 months after randomization.
Secondary	Progression-free survival	Time to progression is evaluated by review and analysis of serial MRI's taken at specific Time to progression is evaluated by review and analysis of serial MRI's taken at specific timepoints	From date of randomization until the date of first documented progression assessed up to 24 months after randomization