- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04015700
Neoantigen-based Personalized DNA Vaccine in Patients With Newly Diagnosed, Unmethylated Glioblastoma
March 6, 2024 updated by: Washington University School of Medicine
A Pilot Study to Assess the Safety, Feasibility, and Immunogenicity of a Neoantigen-based Personalized in Patients With Newly Diagnosed, Unmethylated Glioblastoma
This is a single institution, open-label, single arm, study assessing the safety, feasibility, and immunogenicity of a personalized neoantigen-based vaccine in subjects with newly diagnosed, unmethylated glioblastoma.
Study Overview
Status
Active, not recruiting
Conditions
Study Type
Interventional
Enrollment (Actual)
9
Phase
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Missouri
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Saint Louis, Missouri, United States, 63110
- Washington University School of Medicine
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Description
Inclusion Criteria:
- Newly diagnosed histologically confirmed MGMT unmethylated glioblastoma multiforme (WHO grade IV). Patients with secondary glioblastoma, in particular those who are IDH1 or IDH2 mutant, will not be excluded. High grade gliomas with molecular features of glioblastoma will be included. MGMT methylation status must be confirmed by standard a PCR-based assay.
- Patients who had prior craniotomy with biopsy, subtotal resection, total gross resection, or re-resection will be permitted.
- Consent to genome sequencing and dbGaP-based data sharing and has provided or will provide germline (PBMC) and tumor DNA/RNA samples of adequate quality for sequencing. (Acquisition of specimens for sequencing and the sequencing itself may be done as part of routine care or another research project.)
- At least 18 years of age.
- Karnofsky performance status ≥ 60%
Normal bone marrow and organ function as defined below:
- Absolute neutrophil count ≥ 1,500/mcL
- Platelets ≥ 100,000/mcL
- Total bilirubin ≤ 1.5 x IULN
- AST(SGOT)/ALT(SGPT) ≤ 3.0 x IULN
- Creatinine ≤ IULN OR creatinine clearance ≥ 60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal
- Systemic corticosteroid therapy is permitted provided dosing is no greater than 4 mg per day (dexamethasone or equivalent) on the day of vaccine administration.
- Bevacizumab will be allowed if given for symptomatic control of vasogenic edema and to avoid high dose of corticosteroids.
- Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence) prior to study entry and for the duration of study participation, including at least 5 months (for women of childbearing potential) and at least 7 months (for men) after last dose of study drug. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately.
- Ability to understand and willingness to sign an IRB approved written informed consent document (or that of legally authorized representative, if applicable).
Exclusion Criteria:
- As this study aims to assess the immunogenicity of personalized neoantigen DNA vaccine plus plasmid encoded IL-12 as an adjuvant, no prior immunotherapy will be permitted.
- Inadequate tissue acquisition to allow for neoantigen screening.
- No candidate neoantigen identified during screening.
- A history of other malignancy ≤ 3 years previous with the exception of non-melanoma skin cancer, any in situ cancer that has been successfully resected and cured, treated superficial bladder cancer, or any early-stage solid tumor that was successfully resected without need for adjuvant radiation or chemotherapy.
- Receiving any other investigational agents within 4 weeks of beginning study treatment.
- Known allergy, or history of serious adverse reaction to, vaccines such as anaphylaxis, hives, or respiratory difficulty.
- A history of allergic reactions attributed to compounds of similar chemical or biologic composition to any agents used in the study.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- History of immunodeficiency disorder or autoimmune condition requiring active immunosuppressive therapy. This includes inflammatory bowel disease, ulcerative colitis, Crohn's disease, systemic vasculitis, scleroderma, psoriasis, multiple sclerosis, hemolytic anemia, immune-mediated thrombocytopenia, rheumatoid arthritis, systemic lupus erythematosus, Sjögren's syndrome, sarcoidosis, or other rheumatologic disease or any other medical condition or use of medication which might make it difficult for the patient to complete the full course of treatments or to generate an immune response to vaccines.
- Presence of clinically significant increased intracranial pressure (e.g. impending herniation) or hemorrhage, uncontrolled seizures, or requirement for immediate palliative treatment.
- Pregnant and/or breastfeeding. Women of childbearing potential must have a negative pregnancy test within 7 days of first dose of vaccine.
- Presence of acute or chronic bleeding or clotting disorder that would contraindicate IM injections
Fewer than 2 acceptable sites available for IM injection and CELLECTRA® 2000 EP considering the deltoid and anterolateral quadriceps muscles:
- Tattoos, keloids, or hypertrophic scars located within 2 cm of intended administration site
- Implantable-cardioverter-defibrillator (ICD) or pacemaker (to prevent a life-threatening arrhythmia) that is located ipsilateral to the deltoid injection site (unless deemed acceptable by a cardiologist)
- Any metal implants or implantable medical device within the intended treatment site (i.e. electroporation area).
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Vaccine (GNOS-PV01 + INO-9012)
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-The neoantigen DNA vaccines are also known as DNA plasmid vector expressing tumor-specific antigens.
Other Names:
CELLECTRA® 2000 Device is a system indicated for use to enhance the uptake and expression of plasmid-based biologics in order to enhance vaccine efficacy.
The INO-9012 vials will be supplied by Geneos Therapeutics
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Safety and tolerability of a personalized neoantigen DNA vaccine as measured by dose-limiting toxicities (DLTs)
Time Frame: Up to 30 days
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A DLT will be defined as any grade 3 toxicity or greater according to CTCAE v5 considered at least possibly related to study treatment.
The DLT observation period begins with Cycle 1 Day 1 (date of first vaccine administration) and continues for 30 days
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Up to 30 days
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Feasibility of generating a personalized neoantigen DNA vaccine for patients with newly diagnosed, unmethylated GBM as measured by the ability to identify candidate tumor-specific neoantigens
Time Frame: 4 weeks post-completion of radiotherapy (day 1 of treatment regimen)
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4 weeks post-completion of radiotherapy (day 1 of treatment regimen)
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Feasibility of generating a personalized neoantigen DNA vaccine for patients with newly diagnosed, unmethylated GBM as measured by the ability to manufacture a neoantigen-based DNA vaccine
Time Frame: 4 weeks post-completion of radiotherapy (day 1 of treatment regimen)
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4 weeks post-completion of radiotherapy (day 1 of treatment regimen)
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Feasibility of generating a personalized neoantigen DNA vaccine for patients with newly diagnosed, unmethylated GBM as measured by the ability to administer the vaccine to a patient
Time Frame: 4 weeks post-completion of radiotherapy (day 1 of treatment regimen)
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4 weeks post-completion of radiotherapy (day 1 of treatment regimen)
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Overall survival rate
Time Frame: 12 months
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12 months
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Immunogenicity of a personalized neoantigen DNA vaccine as measured by the ability to generate a measurable neoantigen-specific CD8 T cell response in vaccinated patients
Time Frame: Week 10 post-vaccination
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Week 10 post-vaccination
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Immunogenicity of a personalized neoantigen DNA vaccine as measured by the number of individual neoantigens per number of neoantigens vaccinated against, with which a measurable CD8 T cell-specific response is identified
Time Frame: Week 10 post-vaccination
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Week 10 post-vaccination
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Number of high quality candidates neoantigens present in patients with newly diagnosed GBM
Time Frame: Week 24 post-vaccination
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-High quality neoantigens will be defined as those that meet criteria for inclusion in a vaccine
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Week 24 post-vaccination
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Progression-free survival (PFS) rate
Time Frame: 6 months
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6 months
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Immunogenicity of a personalized neoantigen DNA vaccine as measured by T-cell phenotype, myeloid derived suppressor cell frequency by flow cytometry
Time Frame: Week 24 post-vaccination
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Week 24 post-vaccination
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Immunogenicity of a personalized neoantigen DNA vaccine as measured by diversity of clonality from T cell receptor sequencing
Time Frame: Week 24 post-vaccination
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Week 24 post-vaccination
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Immunogenicity of a personalized neoantigen DNA vaccine as measured by putative antigen specificity from T cell receptor sequencing
Time Frame: Week 24 post-vaccination
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Week 24 post-vaccination
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Investigators
- Principal Investigator: Tanner M Johanns, M.D., Ph.D., Washington University School of Medicine
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
July 14, 2020
Primary Completion (Actual)
May 13, 2022
Study Completion (Estimated)
December 31, 2024
Study Registration Dates
First Submitted
July 8, 2019
First Submitted That Met QC Criteria
July 10, 2019
First Posted (Actual)
July 11, 2019
Study Record Updates
Last Update Posted (Actual)
March 8, 2024
Last Update Submitted That Met QC Criteria
March 6, 2024
Last Verified
March 1, 2024
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Neoplasms by Histologic Type
- Neoplasms
- Neoplasms, Glandular and Epithelial
- Astrocytoma
- Glioma
- Neoplasms, Neuroepithelial
- Neuroectodermal Tumors
- Neoplasms, Germ Cell and Embryonal
- Neoplasms, Nerve Tissue
- Glioblastoma
- Physiological Effects of Drugs
- Immunologic Factors
- Dermatologic Agents
- Keratolytic Agents
- Vaccines
- Coal Tar
Other Study ID Numbers
- 202003072
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
NO
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
Yes
product manufactured in and exported from the U.S.
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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