Trial Title:
A Vaccine (Neoantigen-Targeted ppDC) for the Treatment of H3 G34-mutant Diffuse Hemispheric Glioma
NCT ID:
NCT06342908
Condition:
Diffuse Hemispheric Glioma, H3 G34-Mutant
Conditions: Official terms:
Glioma
Poly I-C
Carboxymethylcellulose Sodium
Poly ICLC
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Not yet recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Procedure
Intervention name:
Biospecimen Collection
Description:
Undergo blood and stool sample collection
Arm group label:
Treatment (PpDC vaccine, Poly ICLC)
Other name:
Biological Sample Collection
Other name:
Biospecimen Collected
Other name:
Specimen Collection
Intervention type:
Biological
Intervention name:
Dendritic Cell Therapy
Description:
Given PpDC vaccine ID
Arm group label:
Treatment (PpDC vaccine, Poly ICLC)
Other name:
Dendritic Cell Vaccine Therapy
Intervention type:
Procedure
Intervention name:
Leukapheresis
Description:
Undergo leukapheresis
Arm group label:
Treatment (PpDC vaccine, Poly ICLC)
Other name:
Leukocytopheresis
Other name:
Therapeutic Leukopheresis
Intervention type:
Procedure
Intervention name:
Magnetic Resonance Imaging
Description:
Undergo MRI
Arm group label:
Treatment (PpDC vaccine, Poly ICLC)
Other name:
Magnetic Resonance
Other name:
Magnetic Resonance Imaging (MRI)
Other name:
Magnetic resonance imaging (procedure)
Other name:
Magnetic Resonance Imaging Scan
Other name:
Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance
Other name:
MR
Other name:
MR Imaging
Other name:
MRI
Other name:
MRI Scan
Other name:
MRIs
Other name:
NMR Imaging
Other name:
NMRI
Other name:
Nuclear Magnetic Resonance Imaging
Other name:
sMRI
Other name:
Structural MRI
Intervention type:
Drug
Intervention name:
Poly ICLC
Description:
Given IM
Arm group label:
Treatment (PpDC vaccine, Poly ICLC)
Other name:
Hiltonol
Other name:
Poly I:Poly C with Poly-L-Lysine Stabilizer
Other name:
poly-ICLC
Other name:
PolyI:PolyC with Poly-L-Lysine Stabilizer
Other name:
Polyinosinic-Polycytidylic Acid Stabilized with Polylysine and Carboxymethylcellulose
Other name:
Polyriboinosinic-Polyribocytidylic Acid-Polylysine Carboxymethylcellulose
Other name:
Stabilized Polyriboinosinic/Polyribocytidylic Acid
Summary:
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.
Detailed description:
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.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Participants between the ages of 18 and 50 years with pathologically-confirmed
diagnosis of (or pathology re-review consistent with) DHG will be enrolled in this
study
- A female participant who has childbearing potential must have negative urine or
serum pregnancy test 72 hours prior to the first dose and be willing to use adequate
method of contraception for course of study and 120 days after last dose
- The participant (or legally acceptable representative if applicable) provides
informed consent (and written assent from minors) for the trial
- An interval of the following durations prior to enrollment:
- At least 28 days from prior surgical resection
- At least 14 days from prior stereotactic biopsy
- Have clinical pathology results, commercial targeted exome sequencing results, or
sufficient archival tumor tissue to confirm DHG following registration. The
following amount of tissue is preferred: 25-50 mg flash frozen tissue block.
Formalin-fixed, paraffin embedded (FFPE) tissue block or 10 FFPE unstained slides
(5µm thick) is acceptable at the discretion of the Sponsor-Investigator
- Have a Karnofsky performance status (KPS) ≥ 70
- Absolute neutrophil count (ANC) ≥ 1500/uL (specimens must be collected within 14
days prior to the start of study treatment)
- Platelets ≥ 100 000/µL (specimens must be collected within 14 days prior to the
start of study treatment)
- Hemoglobin ≥ 9.0 g/dL or ≥ 5.6 mmol/L (specimens must be collected within 14 days
prior to the start of study treatment)
- Criteria must be met without erythropoietin dependency and without packed red
blood cell (pRBC) transfusion within last 2 week
- Creatinine or measured or calculated b creatinine clearance (GFR can also be used in
place of creatinine or CrCl) ≤ 1.5 × ULN or ≥ 30 mL/min for participant with
creatinine levels > 1.5 × institutional ULN (specimens must be collected within 14
days prior to the start of study treatment)
- Creatinine clearance (CrCl) should be calculated per institutional standard.
- Total bilirubin ≤ 1.5 ×ULN or direct bilirubin ≤ ULN for participants with total
bilirubin levels >1.5 × ULN (specimens must be collected within 14 days prior to the
start of study treatment)
- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])
and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) ≤
2.5 × ULN (≤ 5 × ULN for participants with liver metastases) (specimens must be
collected within 14 days prior to the start of study treatment)
- International normalized ratio (INR) OR prothrombin time (PT) activated partial
thromboplastin time (aPTT) ≤ 1.5 × ULN unless participant is receiving anticoagulant
therapy as long as PT or aPTT is within therapeutic range of intended use of
anticoagulants (specimens must be collected within 14 days prior to the start of
study treatment)
Exclusion Criteria:
- Age > 50 years or < 18 years
- Have had more than 1 separately-treated recurrences of the index tumor
- A woman of child-bearing potential who has a positive urine pregnancy test within 72
hours prior to enrollment. If the urine test is positive or cannot be confirmed as
negative, a serum pregnancy test will be required
- Has received prior systemic anti-cancer therapy including investigational agents
within 2 weeks prior to enrollment. Note: Participants must have recovered from all
adverse events (AEs) due to previous therapies to ≤ grade 1 or baseline.
Participants with ≤ grade 2 neuropathy may be eligible
- Has received a live vaccine within 30 days prior to the first dose of study drug.
Examples of live vaccines include, but are not limited to, the following: measles,
mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus
Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for
injection are generally killed virus vaccines and are allowed; however, intranasal
influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed
- Is currently participating in or has participated in a study of an investigational
agent or has used an investigational device within 4 weeks prior to the first dose
of study treatment. Note: Participants who have entered the follow-up phase of an
investigational study may participate as long as it has been 4 weeks after the last
dose of the previous investigational agent
- Has a diagnosis of immunodeficiency or is receiving chronic systemic corticosteroid
therapy (dosing exceeding 1 mg/kg/day of prednisone equivalent) or any other form of
immunosuppressive therapy within 7 days prior to the first dose of study drug
- Has a known additional malignancy that is progressing or has required active
treatment within the past 3 years. Note: Participants with basal cell carcinoma of
the skin squamous cell carcinoma of the skin, or carcinoma in situ (e.g. breast
carcinoma, cervical cancer in situ) that have undergone potentially curative therapy
are not excluded
- Has active autoimmune disease that has required systemic treatment in the past 2
years (i.e. with use of disease modifying agents, corticosteroids or
immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or
physiologic corticosteroid replacement therapy for adrenal or pituitary
insufficiency, etc.) is not considered a form of systemic treatment
- Has a history of (non-infectious) pneumonitis that required steroids or has current
pneumonitis
- Has an active infection requiring systemic therapy
- Has a known history of hepatitis B (defined as hepatitis B surface antigen [HBsAg]
reactive) or known active hepatitis C virus (defined as hepatitis C virus [HCV]
ribonucleic acid [RNA] is detected) infection. Note: no testing for hepatitis B and
hepatitis C is required unless mandated by local health authority
- Has a known history of active tuberculosis (Bacillus tuberculosis)
- Has a history or current evidence of any condition, therapy, or laboratory
abnormality that might confound the results of the study, interfere with the
participant's participation for the full duration of the study, or is not in the
best interest of the participant to participate, in the opinion of the treating
investigator
- Has known psychiatric or substance abuse disorders that would interfere with
cooperation with the requirements of the trial
- Kidney dysfunction precluding administration of gadolinium-based contrast
- Is pregnant or breastfeeding, or expecting to conceive within the projected duration
of the study, starting with the screening visit through 120 days after the last dose
of trial treatment
Gender:
All
Minimum age:
18 Years
Maximum age:
50 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
UCLA / Jonsson Comprehensive Cancer Center
Address:
City:
Los Angeles
Zip:
90095
Country:
United States
Contact:
Last name:
Sichen C. Li
Phone:
310-592-9091
Email:
sichenli@mednet.ucla.edu
Investigator:
Last name:
Anthony C. Wang, MD
Email:
Principal Investigator
Start date:
December 8, 2024
Completion date:
January 9, 2028
Lead sponsor:
Agency:
Jonsson Comprehensive Cancer Center
Agency class:
Other
Source:
Jonsson Comprehensive Cancer Center
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06342908
