This phase I trial tests the safety and side effects, and best dose of a vaccine (neoantigen-target ppDC) in treating patients with H3 G34-mutant diffuse hemispheric glioma. Vaccines made from the patient's own white blood cells and peptide-pulsed dendritic cells may help the body build an effective immune response to kill tumor cells. Giving neoantigen-targeted ppDC may be safe, tolerable and/or effective in treating patients with diffuse hemispheric glioma with a H3 G34 mutation.
PRIMARY OBJECTIVE: I. To evaluate the safety and feasibility of neoantigen-targeted ppDC in adult patients with diffuse hemispheric glioma (DHG). SECONDARY OBJECTIVES: I. To evaluate the immunogenicity of neoantigen-targeted ppDC in adult patients with DHG. II. To determine whether neoantigen-targeted ppDC facilitates systemic T cell-mediated adaptive immune activation in DHG patients. III. To determine whether neoantigen-targeted ppDC facilitates a target-specific anti-tumor T cell expansion in DHG patients. IV. To determine whether pro-inflammatory phenotypic changes in systemic immune cell populations are detected in peripheral blood in response to neoantigen-targeted ppDC vaccination in DHG patients. EXPLORATORY OBJECTIVES: I. To estimate the potential efficacy of neoantigen-targeted ppDC in DHG patients. II. To correlate physiologic and metabolic magnetic resonance imaging (MRI) with systemic immunologic response after neoantigen-targeted ppDC in DHG patients. III. To isolate and sequence immunodominant anti-tumor T cell T-cell receptor (TCRs) stimulated by neoantigen-targeted ppDC in DHG patients. IV. To explore whether study participants demonstrating immune-reactive responses to neoantigen-targeted ppDC harbor significantly different gastrointestinal microbiota profiles in comparison to unresponsive participants. OUTLINE: Patients undergo leukapheresis 10 days prior to first injection. Patients then receive ppDC intradermally (ID) with poly ICLC intramuscularly (IM) in both arms every 2 weeks (Q2W) for total 3 doses and then every 6 months for up to 3 doses. Patients undergo magnetic resonance imaging (MRI) throughout the trial. Patients also undergo blood sample collection throughout the trial in addition to stool sample collection during screening and on the trial. After completion of study treatment, patients are followed up at 30 and 120 days and then up to 24 months.
Study Type
INTERVENTIONAL
Allocation
NA
Undergo blood and stool sample collection
Given PpDC vaccine ID
Undergo leukapheresis
UCLA / Jonsson Comprehensive Cancer Center
Los Angeles, California, United States
Incidence of regimen-limiting toxicities
Will be graded in severity according to Common Terminology Criteria for Adverse Events version 5.0 (CTCAE, v 5.0) guidelines, monitoring for 30 days following each dose for adverse event recording, and for 120 days following each dose for serious adverse event recording.
Time frame: Up to 120 days after last dose
Significant increase in gamma-interferon (IFN) gene expression signature
Peripheral blood mononuclear cells (PBMCs) will be evaluated by ribonucleic acid sequence for significant increase in gamma-interferon (IFN) gene expression signature, comparing baseline PBMCs with PBMCs obtained after each dose phase of peptide-pulsed dendritic cells (ppDC).
Time frame: Up to 4 years
Significant clonal T cell expansion
PBMCs obtained before and after each ppDC dose phase will be analyzed for significant clonal T cell expansion by bulk V beta-T cell receptor (TCR) sequencing.
Time frame: Up to 4 years
Targets of clonal cytotoxic T cell expansion
The targets of clonal cytotoxic T cell expansion in PBMCs in response to ppDC assessed by using target-specific major histocompatibility complex (MHC) oligomers binding assays.
Time frame: Up to 4 years
Pro-inflammatory phenotypic changes in immune cell populations
The pro-inflammatory phenotypic changes in immune cell populations in response to ppDC assessed by cellular indexing of transcriptomes, epitopes-sequencing and a multi-color fluorescence-activated cell sorting panel.
Time frame: Up to 4 years
Changes in immune cell subset expansion and contraction in T cell and myeloid-derived cell populations
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Purpose
TREATMENT
Masking
NONE
Enrollment
6
Undergo MRI
Given IM
The changes in immune cell subset expansion and contraction in T cell and myeloid-derived cell populations in response to ppDC assessed by cellular indexing of transcriptomes and epitopes-sequencing and a multi-color fluorescence-activated cell sorting panel.
Time frame: Up to 4 years
Changes of immune cell markers profile in T cell and myeloid-derived cell populations
The profile changes of the markers for immune cell activity, suppression, and exhaustion in T cell and myeloid-derived cell populations in response to ppDC assessed by cellular indexing of transcriptomes and epitopes-sequencing and a multi-color fluorescence-activated cell sorting panel.
Time frame: Up to 4 years