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

Primary Purpose

Glioblastoma Multiforme of Brain

Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
TVI-Brain-1
Standard of Care
Radiotherapy
Temozolomide
Sponsored by
TVAX Biomedical
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Glioblastoma Multiforme of Brain

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • University of Kansas Medical CenterRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Standard of Care

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

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

Survival
All Subjects will be evaluated and contacted to evaluate their status

Secondary Outcome Measures

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

Full Information

First Posted
December 22, 2022
Last Updated
September 25, 2023
Sponsor
TVAX Biomedical
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1. Study Identification

Unique Protocol Identification Number
NCT05685004
Brief Title
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

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
September 15, 2023 (Actual)
Primary Completion Date
December 2025 (Anticipated)
Study Completion Date
March 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
TVAX Biomedical

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Glioblastoma Multiforme of Brain

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Masking
Outcomes Assessor
Masking Description
Blinded over-read of sequential MRI assessments
Allocation
Randomized
Enrollment
96 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Standard of Care
Arm Type
Active Comparator
Arm Description
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.
Arm Title
Interventional TVI-Brain-1 Autologous Vaccine and activated autologous blood-derived t cells
Arm Type
Experimental
Arm Description
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.
Intervention Type
Biological
Intervention Name(s)
TVI-Brain-1
Intervention Description
Attenuated autologous cancer cells and activated autologous blood-derived t cells
Intervention Type
Procedure
Intervention Name(s)
Standard of Care
Intervention Description
Surgery for tumor removal or debulking to minimize tumor burden
Intervention Type
Radiation
Intervention Name(s)
Radiotherapy
Intervention Description
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
Drug
Intervention Name(s)
Temozolomide
Other Intervention Name(s)
Chemotherapy
Intervention Description
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 .
Primary Outcome Measure Information:
Title
Survival
Description
All Subjects will be evaluated and contacted to evaluate their status
Time Frame
From date of randomization until the date of death from any cause assessed up to 24 months after randomization.
Secondary Outcome Measure Information:
Title
Progression-free survival
Description
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
Time Frame
From date of randomization until the date of first documented progression assessed up to 24 months after randomization
Other Pre-specified Outcome Measures:
Title
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Description
Assessment of changes in patient through Physical Examination
Time Frame
Through study completion, an average of 2 years
Title
Immunogenicity
Description
Delayed-type hypersensitivity (DTH) skin testing using attenuated autologous cancer cells will be performed to assess the immunogenicity of the Subject's cancer.
Time Frame
Assessed at 24 hours after each vaccine administration
Title
Other genetic and immunologic parameters
Description
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
Time Frame
Assessed at 24 hours after each vaccine administration

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Jean Aguiar
Phone
1 913 492 2221
Email
info@tvaxbiomedical.com
First Name & Middle Initial & Last Name or Official Title & Degree
President and CEO
Phone
1 913 492 2221
Email
info@tvaxbiomedical.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jean Aguiar, APRN
Organizational Affiliation
TVAX Biomedical, Inc
Official's Role
Study Director
Facility Information:
Facility Name
University of Kansas Medical Center
City
Olathe
State/Province
Kansas
ZIP/Postal Code
66061
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Tolga Tuncer, MD
Phone
913-588-1227
Email
ttuncer@kumc.edu
First Name & Middle Initial & Last Name & Degree
Anna Davis
Phone
913-588-0242
Email
adavis43@kumc.edu

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
1407433
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.
Results Reference
background
PubMed Identifier
1403119
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.
Results Reference
background
PubMed Identifier
9225000
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.
Results Reference
background
PubMed Identifier
16817692
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.
Results Reference
background
PubMed Identifier
10570748
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.
Results Reference
background

Learn more about this trial

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

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