Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Neoantigen-based Personalized DNA Vaccine in Patients With Newly Diagnosed, Unmethylated Glioblastoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04015700
Recruitment Status : Recruiting
First Posted : July 11, 2019
Last Update Posted : August 6, 2020
Sponsor:
Collaborator:
Geneos Therapeutics
Information provided by (Responsible Party):
Washington University School of Medicine

Tracking Information
First Submitted Date  ICMJE July 8, 2019
First Posted Date  ICMJE July 11, 2019
Last Update Posted Date August 6, 2020
Actual Study Start Date  ICMJE July 14, 2020
Estimated Primary Completion Date October 31, 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 23, 2019)
  • Safety and tolerability of a personalized neoantigen DNA vaccine as measured by dose-limiting toxicities (DLTs) [ Time Frame: Up to 30 days ]
    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
  • 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) ]
  • 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) ]
  • 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) ]
Original Primary Outcome Measures  ICMJE
 (submitted: July 10, 2019)
  • Safety and tolerability of a personalized neoantigen DNA vaccine as measured by dose-limiting toxicities (DLTs) [ Time Frame: Up to 90 days ]
    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 in Cohort A; 60 days for Cohorts C, and E; and 90 days for Cohorts B and D.
  • 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) ]
  • 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) ]
  • 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) ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 23, 2019)
  • 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 ]
  • 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 ]
  • Number of high quality candidates neoantigens present in patients with newly diagnosed GBM [ Time Frame: Week 24 post-vaccination ]
    -High quality neoantigens will be defined as those that meet criteria for inclusion in a vaccine
  • Progression-free survival (PFS) rate [ Time Frame: 6 months ]
    • PFS=duration of time from start of treatment to time of progression or death, whichever occurs first.
    • Progression: any of the following
      • ≥ 25% increase in sum products of perpendicular diameters of enhancing lesions compared with the smallest tumor measurement obtained either at baseline or best response, on stable or increasing doses of corticosteroids*. The absolute increase in any dimension must be at least 5mm when calculating the products.
      • Significant increase in T2/FLAIR nonenhancing lesion on stable/increasing doses of corticosteroids compared with baseline scan or best response after initiation of therapy* not caused by comorbid events
      • New measureable lesion.
      • Clear clinical deterioration not attributable to other causes apart from the tumor (e.g. seizures, medication adverse effects, complications of therapy, cerebrovascular events, infection, and so on) or changes in corticosteroid dose.
  • Overall survival rate [ Time Frame: 12 months ]
  • 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 ]
  • Immunogenicity of a personalized neoantigen DNA vaccine as measured by diversity of clonality from T cell receptor sequencing [ Time Frame: Week 24 post-vaccination ]
  • Immunogenicity of a personalized neoantigen DNA vaccine as measured by putative antigen specificity from T cell receptor sequencing [ Time Frame: Week 24 post-vaccination ]
Original Secondary Outcome Measures  ICMJE
 (submitted: July 10, 2019)
  • Immunogenicity of a personalized neoantigen DNA vaccine as measured by the ability to generate a measureable neoantigen-specific CD8 T cell response in vaccinated patients [ Time Frame: Week 24 post-vaccination ]
  • 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 13 post-vaccination ]
  • Number of high quality candidates neoantigens present in patients with newly diagnosed GBM [ Time Frame: Week 24 post-vaccination ]
    -High quality neoantigens will be defined as those that meet criteria for inclusion in a vaccine
  • Progression-free survival (PFS) rate [ Time Frame: 6 months ]
    • PFS=duration of time from start of treatment to time of progression or death, whichever occurs first.
    • Progression: any of the following
      • ≥ 25% increase in sum products of perpendicular diameters of enhancing lesions compared with the smallest tumor measurement obtained either at baseline or best response, on stable or increasing doses of corticosteroids*. The absolute increase in any dimension must be at least 5mm when calculating the products.
      • Significant increase in T2/FLAIR nonenhancing lesion on stable/increasing doses of corticosteroids compared with baseline scan or best response after initiation of therapy* not caused by comorbid events
      • New measureable lesion.
      • Clear clinical deterioration not attributable to other causes apart from the tumor (e.g. seizures, medication adverse effects, complications of therapy, cerebrovascular events, infection, and so on) or changes in corticosteroid dose.
  • Overall survival rate [ Time Frame: 12 months ]
  • 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 ]
  • Immunogenicity of a personalized neoantigen DNA vaccine as measured by diversity of clonality from T cell receptor sequencing [ Time Frame: Week 24 post-vaccination ]
  • Immunogenicity of a personalized neoantigen DNA vaccine as measured by putative antigen specificity from T cell receptor sequencing [ Time Frame: Week 24 post-vaccination ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Neoantigen-based Personalized DNA Vaccine in Patients With Newly Diagnosed, Unmethylated Glioblastoma
Official Title  ICMJE A Pilot Study to Assess the Safety, Feasibility, and Immunogenicity of a Neoantigen-based Personalized in Patients With Newly Diagnosed, Unmethylated Glioblastoma
Brief Summary 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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Glioblastoma
Intervention  ICMJE
  • Biological: Personalized neoantigen DNA vaccine supplied by Geneos Therapeutics
    -The neoantigen DNA vaccines are also known as DNA plasmid vector expressing tumor-specific antigens.
    Other Names:
    • GNOS-PV01
    • Vaccine
  • Device: CELLECTRA®2000 EP Device supplied by Geneos Therapeutics
    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.
  • Drug: Plasmid encoded IL-12
    The INO-9012 vials will be supplied by Geneos Therapeutics
    Other Name: INO-9012
Study Arms  ICMJE Experimental: Vaccine (GNOS-PV01 + INO-9012)
  • Standard radiation therapy will be administered per standard of care and is outside the scope of this study.
  • GNOS-PV01 + INO-9012 will be given on Days 1, 22, and 43 of Cycle 1 and then on Day 1 of each subsequent cycle beginning with Cycle 2 for a total of 6 cycles or until intolerance or progression
Interventions:
  • Biological: Personalized neoantigen DNA vaccine supplied by Geneos Therapeutics
  • Device: CELLECTRA®2000 EP Device supplied by Geneos Therapeutics
  • Drug: Plasmid encoded IL-12
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: September 23, 2019)
6
Original Estimated Enrollment  ICMJE
 (submitted: July 10, 2019)
30
Estimated Study Completion Date  ICMJE July 31, 2024
Estimated Primary Completion Date October 31, 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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).
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Tanner M Johanns, M.D., Ph.D. 314-273-2723 tjohanns@wustl.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04015700
Other Study ID Numbers  ICMJE 202003072
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
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
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Washington University School of Medicine
Study Sponsor  ICMJE Washington University School of Medicine
Collaborators  ICMJE Geneos Therapeutics
Investigators  ICMJE
Principal Investigator: Tanner M Johanns, M.D., Ph.D. Washington University School of Medicine
PRS Account Washington University School of Medicine
Verification Date August 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP