Personalized Immunotherapy for Glioblastoma
Recruiting in Palo Alto (17 mi)
+9 other locations
Overseen byMichael Salacz, MD
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2 & 3
Recruiting
Sponsor: TVAX Biomedical
Must not be taking: Glucocorticoids
Disqualifiers: Second malignancy, Autoimmune disease, others
No Placebo Group
Prior Safety Data
Trial Summary
What is the purpose of this trial?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.
Will I have to stop taking my current medications?
The trial requires that you are not currently taking glucocorticoids and have been off them for at least 24 hours before vaccination and T cell infusion. Other medications are not specified, so it's best to discuss with the trial team.
What data supports the effectiveness of this treatment for glioblastoma?
Research shows that combining temozolomide (a chemotherapy drug) with radiation therapy can help control glioblastoma, a type of brain cancer. Studies have found that this combination can enhance the immune response against the tumor and lead to partial tumor shrinkage in some patients.
12345Is personalized immunotherapy for glioblastoma safe?
Temozolomide, a drug used in glioblastoma treatment, is generally considered safe but can cause severe blood-related side effects (myelotoxicity) and skin reactions in some patients. Combining it with other treatments like radiation may increase the risk of side effects.
678910What makes the treatment for glioblastoma in this trial unique?
This treatment is unique because it combines personalized immunotherapy with standard treatments like radiotherapy and temozolomide (a drug that can cross the blood-brain barrier and kill cancer cells), potentially enhancing the body's immune response against glioblastoma.
2351112Eligibility Criteria
This trial is for adults with newly diagnosed MGMT unmethylated glioblastoma who haven't been treated before. They need enough tumor tissue from surgery to make a vaccine, normal kidney and liver function, no current steroid use, good physical function (Karnofsky score > 60), expected to live more than 12 weeks, and specific blood cell counts within the required range. Pregnant individuals or those planning pregnancy within a year are excluded.Inclusion Criteria
My hemoglobin level is above 10 g/dL.
Lymphocyte count is > 1,000 cells/mcL of blood
I have a new diagnosis of a specific brain cancer (glioblastoma) without prior treatment.
+8 more
Exclusion Criteria
Psychological, familial, sociological or geographical conditions that do not permit adequate medical follow-up and compliance with the study protocol
I need steroids to manage brain swelling.
I have another cancer that is not in remission, except for skin cancer.
+3 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Surgery and Initial Treatment Preparation
Subjects undergo surgical resection of their cancer and are tapered off steroids. The first vaccination of TVI-Brain-1 is administered approximately 7-14 days following surgery.
2-3 weeks
Chemoradiotherapy
Subjects receive combined radiotherapy and chemotherapy with temozolomide, followed by leukapheresis to collect immune T cells.
5 weeks
Immunotherapy and T Cell Infusion
Subjects receive a second vaccination, undergo leukapheresis, and are infused with activated effector T cells followed by a 10-day course of low-dose interleukin 2 (IL-2).
3-4 weeks
Follow-up
Participants are monitored for safety and effectiveness after treatment with regular MRIs and assessments.
24 months
Participant Groups
The study tests TVI-Brain-1 immunotherapy combined with standard care versus standard care alone in treating glioblastoma. It involves creating a personalized vaccine from the patient's cancer cells to boost immune response and infusing expanded T cells back into the patient.
2Treatment groups
Experimental Treatment
Active Control
Group I: Interventional TVI-Brain-1 Autologous Vaccine and activated autologous blood-derived t cellsExperimental Treatment4 Interventions
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 II: Standard of CareActive Control3 Interventions
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.
Radiotherapy is already approved in European Union, United States, Canada, Japan, China, Switzerland for the following indications:
🇪🇺 Approved in European Union as Radiation therapy for:
- Various cancers including breast cancer, lung cancer, prostate cancer, and soft tissue sarcoma
🇺🇸 Approved in United States as Radiation therapy for:
- Various cancers including breast cancer, lung cancer, prostate cancer, and soft tissue sarcoma
🇨🇦 Approved in Canada as Radiation therapy for:
- Various cancers including breast cancer, lung cancer, prostate cancer, and soft tissue sarcoma
🇯🇵 Approved in Japan as Radiation therapy for:
- Various cancers including breast cancer, lung cancer, prostate cancer, and soft tissue sarcoma
🇨🇳 Approved in China as Radiation therapy for:
- Various cancers including breast cancer, lung cancer, prostate cancer, and soft tissue sarcoma
🇨🇭 Approved in Switzerland as Radiation therapy for:
- Various cancers including breast cancer, lung cancer, prostate cancer, and soft tissue sarcoma
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Center for NeurosciencesTucson, AZ
Providence St. VincentPortland, OR
Capital HealthNewark, NJ
Aaron MammoserAtlanta, GA
More Trial Locations
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Who Is Running the Clinical Trial?
TVAX BiomedicalLead Sponsor
FDA Office of Orphan Products DevelopmentCollaborator
References
Pathological changes after autologous formalin-fixed tumor vaccine therapy combined with temozolomide for glioblastoma - three case reports - . [2022]Temozolomide (TMZ), an alkylating agent widely used for patients with glioblastoma multiforme (GBM), has the potential to enhance the acquired immune response to GBM. Here, we describe 3 cases of GBM patients treated with autologous formalin-fixed tumor vaccine (AFTV) combined with TMZ. All cases demonstrated pathological changes associated with the therapy. After a 4-week break from the standard initial treatments, 1 patient with primary GBM and 2 patients with secondary GBM received adjuvant TMZ for 5 days combined with AFTV injection and were subsequently treated with multiple cycles of adjuvant TMZ for 5 days every 28 days (AFTV/TMZ therapy). Adverse effects related to AFTV plus TMZ were very minor in all patients. Magnetic resonance imaging revealed partial response in 2 patients. CD3(+)CD8(+) lymphocytes were frequently detected in surgical specimens and MIB-1 labeling index in 2 cases decreased after AFTV/TMZ therapy. AFTV/TMZ therapy is suitable for larger scale clinical trials.
Radiosensitization of Glioma Cells by Temozolomide (TMZ): A Colony Formation Assay. [2022]Glioblastoma is one of the most radioresistant cancers. It is suggested that combination of radiotherapy with other cancer treatment modalities may increase control of tumor. Temozolomide (TMZ) is one of the most known drugs for glioblastoma. It has shown that TMZ via induction of mutation and cell death can kill glioma cells.
The outcomes of concomitant radiation plus temozolomide followed by adjuvant temozolomide for newly diagnosed high grade gliomas: the preliminary results of single center prospective study. [2020]Temozolomide (TMZ) is an oral alkylating agent with demonstrated efficacy as second-line therapy for patients with recurrent anaplastic astrocytoma and glioblastoma multiforme (GBM). We reported the preliminary results of the treatment with concomitant radiation therapy (RT) plus TMZ followed by adjuvant TMZ therapy in patients with newly diagnosed high grade gliomas (HGG) to determine the safety, tolerability, and efficacy.
Radiosensitizing effects of temozolomide observed in vivo only in a subset of O6-methylguanine-DNA methyltransferase methylated glioblastoma multiforme xenografts. [2022]Concurrent temozolomide (TMZ) and radiation therapy (RT) followed by adjuvant TMZ is standard treatment for patients with glioblastoma multiforme (GBM), although the relative contribution of concurrent versus adjuvant TMZ is unknown. In this study, the efficacy of TMZ/RT was tested with a panel of 20 primary GBM xenografts.
Phase I/IIa trial of fractionated radiotherapy, temozolomide, and autologous formalin-fixed tumor vaccine for newly diagnosed glioblastoma. [2023]Temozolomide (TMZ) may enhance antitumor immunity in patients with glioblastoma multiforme (GBM). In this paper the authors report on a prospective Phase I/IIa clinical trial of fractionated radiotherapy (FRT) concomitant with TMZ therapy, followed by treatment with autologous formalin-fixed tumor vaccine (AFTV) and TMZ maintenance in patients with newly diagnosed GBM.
Clinical and Genetic Factors Associated With Severe Hematological Toxicity in Glioblastoma Patients During Radiation Plus Temozolomide Treatment: A Prospective Study. [2018]Temozolomide (TMZ) administered daily with radiation therapy (RT) for 6 weeks, followed by adjuvant TMZ for 6 cycles, is the standard therapy for newly diagnosed glioblastoma (GBM) patients. Although TMZ is considered to be a safe drug, it has been demonstrated to cause severe myelotoxicity; in particular, some case reports and small series studies have reported severe myelotoxicity developing during TMZ and concomitant RT. We performed a prospective study to analyze the incidence of early severe myelotoxicity and its possible clinical and genetic factors.
Two cases of cutaneous drug eruption associated with temozolomide therapy for glioblastoma. [2018]Glioblastoma is the most common form of primary brain cancer. Its treatment involves surgery, radiotherapy, and chemotherapy with temozolomide (tmz), which is an oral alkylating agent. To the best of our knowledge, few dermatologic side effects of tmz have been described. We report two cases of cutaneous drug eruption caused by tmz during and after radiochemotherapy treatment. In the first case, all tests were negative, but the clinical history and the time of onset supported an allergy to tmz. In the second case, an allergy to tmz was proved by a positive lymphocyte activation test. In this context, our study is one of a very few trying to determine dermatologic side effects by applicable tests used in routine practice.
Safety and efficacy of Gliadel wafers for newly diagnosed and recurrent glioblastoma. [2018]Combining Gliadel wafers and radiochemotherapy with TMZ may carry the risk of increased adverse events (AE). We analyzed the efficacy and safety in patients with glioblastoma who underwent multimodal treatment with implantation of Gliadel wafers.
Response and safety of whole-brain radiotherapy plus temozolomide for patients with brain metastases of non-small-cell lung cancer: A meta-analysis. [2022]The aim of the present work was to investigate the response and safety of whole-brain radiotherapy (WBRT) plus temozolomide (TMZ) for patients with brain metastases of non-small-cell lung cancer (NSCLC).
Oral temozolomide in heavily pre-treated brain metastases from non-small cell lung cancer: phase II study. [2018]The primary tumour type most likely to metastasize to the brain is lung cancer. In heavily pre-treated patients, limited therapeutic option is available and the results of availability therapies reported in literature are disappointing. The present phase II study was designed to assess the efficacy and safety of temozolomide (TMZ) as palliative treatment for brain metastases (BrM) in NSCLC patients pre-treated with WBRT and at least one line of chemotherapy for metastatic brain disease.
Temozolomide for treating brain metastases. [2019]The metastasis of solid tumors to the brain is associated with a poor prognosis despite aggressive treatment. Available treatment options are limited, as many chemotherapeutic agents do not penetrate the blood-brain barrier. Temozolomide (Temodar in the United States, Temodal globally; Schering Corporation, Kenilworth, NJ) is a novel chemotherapeutic agent with a good safety profile that crosses the blood-brain barrier and has shown activity against many human solid tumors. In two phase II trials of temozolomide in heavily pretreated patients with various solid tumor brain metastases, temozolomide was safe and generally well tolerated and showed clinical activity, with three partial responses and 19 disease stabilizations. Results of a third randomized phase II trial of concurrent administration of temozolomide and radiation therapy followed by adjuvant temozolomide therapy compared with radiation alone showed a higher rate of complete and partial responses (objective response of 96% v 67%) and significantly more complete responses (38% v 33%, P =.017), primarily in patients with newly diagnosed brain and lung metastases.
Future directions for temozolomide therapy. [2019]Although the initial indications of temozolomide (Temodar in the United States, Temodal globally; Schering Corporation, Kenilworth, NJ) therapy are for refractory central nervous system malignancies (anaplastic astrocytoma in the United States and Europe, glioblastoma multiforme in Europe), a number of clinical trials are planned or ongoing to evaluate the efficacy and safety of temozolomide in newly diagnosed glioma, oligodendroglioma, pediatric glioma, brain metastases, metastatic melanoma, and other systemic tumors. Also under investigation are modifications to the temozolomide dosing schedule, other routes of administration, and treatment regimens that include temozolomide in combination with other chemotherapeutic and biologic agents. Temozolomide has the potential to be a useful agent in the treatment of a variety of cancers.