This early phase I trial tests the safety, side effects and how well medication combinations of dasatinib, quercetin, fisetin, temozolomide, LMP744, and autologous tumor lysate particle only (TLPO) vaccine work in treating patients with glioma for which the patient has received treatment in the past (previously treated) and for tumor cells that remain after attempts to treat the tumor have been made (residual disease). Dasatinib is in a class of medications called tyrosine kinase inhibitors. It works by blocking the action of an abnormal protein that signals tumor cells to multiply, which may help keep tumor cells from growing. Quercetin and fisetin are compounds found in plants. They have antioxidant and anti-inflammatory properties and help remove senescent cells, older or damaged cells that have stopped dividing but don't die off as they should and build up in tissues over time. Senescent cells may cause inflammation or damage to nearby healthy cells. Temozolomide is in a class of medications called alkylating agents. It works by damaging the cell's deoxyribonucleic acid (DNA) and may kill tumor cells and slow down or stop tumor growth. LMP744 works by interfering with a protein that tumor cells use to copy and repair their DNA. By blocking this repair process, the drug causes DNA damage so that tumor cells cannot survive. The autologous TLPO vaccine is made using material from a patient's own tumor. It delivers the tumor material to immune cells so they can learn to recognize and attack the cancer. Giving medication combinations of dasatinib, quercetin, fisetin, temozolomide, LMP744, and autologous TLPO vaccine may be safe, tolerable and/or effective in treating patients with previously treated glioma with residual disease.
Age ≥ 18 years
Prior diagnosis of a glioma treated with chemotherapy and/or radiation with stable disease based on Response Assessment in Neuro-Oncology (RANO) criteria
Must have IDH-mutant OR MGMT-methylated glioma
NOTE: Patients with any radiographic evidence of residual disease are eligible
Pregnant persons
Nursing persons
Persons of childbearing potential and persons able to father a child who are unwilling to employ adequate contraception
Patients who are not appropriate medical candidates due to current or past medical history or uncontrolled concurrent illness which limits safety of or compliance to study proceedings
Sequential
Biospecimen Collection
Procedure/SurgeryUndergo blood sample collection
Dasatinib
DrugGiven PO
Fisetin
DrugGiven PO
Magnetic Resonance Imaging
Procedure/SurgeryUndergo MRI
Patient Observation
Other interventionReceive rest and take no treatment
Positron Emission Tomography
Procedure/SurgeryUndergo amino acid PET scan (optional)
Quercetin
DrugGiven PO
Temozolomide
DrugGiven PO
Topoisomerase-1 Inhibitor LMP744
DrugGiven IV
Single Agent Therapy
DrugGiven autologous TLPO vaccine ID
9
Treatment groupsSee each treatment group below.
Completion of 3 cycles
Will evaluate feasibility of serially screening multiple candidate therapies or combinations based on individualized empiric biological feedback from biospecimens and imaging. This will be measured as the percentage of patients successfully completing 3 cycles of drug administration (study visits). A cycle is 35 +/- 7 days. Regimen will be considered feasible if at least 2/3 of patients can achieve this target.
Turnaround time for scan and marker data
Will also evaluate feasibility as the turnaround time for scan and marker data that is used to determine if patients should stay on current therapy or move to the next regimen. The outcomes will be cycle-specific. A cycle is 35 +/- 7 days. The target for this is a mean turnaround time of 3 days; if the maximum turnaround time exceeds 5 days, this will prompt an evaluation of process to identify barriers.
Incidence of adverse events
Will assess the safety of this algorithm-based approach to individualized therapeutic drug combinations in patients with pre-recurrent central nervous system tumors. The study drugs will be considered well-tolerated with no grade 3 or higher adverse event attributable to the drugs in the 10 patients. Adverse events will be evaluated per the Common Terminology Criteria for Adverse Events (CTCAE) version 5 criteria and summarized by type and severity as well as perceived attribution to study treatment for each of the regimens received by patients.
Change in senescence-associated proteins
Will evaluate relative change from baseline in enrichment for a panel of senescence-associated proteins in cerebrospinal fluid (CSF) for each sequentially administered senolytic agent. An effective senolytics regimen will decrease CSF senescence associated secretory phenotype, including monocyte chemoattractant protein-1 levels, by at least 25%.
Cell-free mitochondrial deoxyribonucleic acid (DNA)
Will evaluate the percentage change in cell-free mitochondrial DNA. An effective senolytics regimen will decrease cell-free mitochondrial DNA by at least 25%.
2-Hydroxyglutarate (2-HG)
Will evaluate the percentage change in 2-HG.
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