Clinical trial NCT05685004: Study of Neoantigen-specific Adoptive T Cell Therapy for Newly Diagnosed MGMT Negative Glioblastoma Multiforme (GBM)
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)
Study type: INTERVENTIONAL
Overall status: SUSPENDED
Phase: PHASE2
PHASE3
Conditions: Glioblastoma Multiforme of Brain
Lead sponsor: TVAX Biomedical
Sponsor class: INDUSTRY
First posted: 2023-01-13
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Survival
timeFrame: From date of randomization until the date of death from any cause assessed up to 24 months after randomization.
Secondary outcomes:
measure: Progression-free survival
timeFrame: From date of randomization until the date of first documented progression assessed up to 24 months after randomization
Other outcomes:
measure: Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
timeFrame: Through study completion, an average of 2 years
measure: Immunogenicity
timeFrame: Assessed at 24 hours after each vaccine administration
measure: Other genetic and immunologic parameters
timeFrame: Assessed at 24 hours after each vaccine administration
Locations:
city: Tucson
country: United States
facility: Center for Neurosciences
state: Arizona
city: Los Angeles
country: United States
facility: Cedar-Sanai Medical Center
state: California
city: Los Angeles
country: United States
facility: University of Southern California Keck School of Medicine
state: California
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: Atlanta
country: United States
facility: Aaron Mammoser
state: Georgia
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Pennington
country: United States
facility: Capital Health
state: New Jersey
city: Portland
country: United States
facility: Providence St. Vincent
state: Oregon
Study officials:
affiliation: TVAX Biomedical, Inc
name: Jean Aguiar, APRN
role: STUDY_DIRECTOR
References:
citation: 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.
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.
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.
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.
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.