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GlioblastomaPhase 1NCT03422094

Neoantigen-based Personalized Vaccine Combined With Immune Checkpoint Blockade Therapy in Patients With Newly Diagnosed, Unmethylated Glioblastoma

A Phase 1 study testing NeoVax, Nivolumab and Ipilimumab in people with Glioblastoma, run by Washington University School of Medicine at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

This is a single institution, open-label, multi-arm, pilot study assessing the safety, feasibility, and immunogenicity of a personalized neoantigen-based vaccine plus poly-ICLC (NeoVax) combined with immune checkpoint inhibitors in subjects with newly diagnosed, unmethylated glioblastoma. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Glioblastoma
What is being tested?
NeoVax, Nivolumab and Ipilimumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
3 participants
Where
1 siteUnited States
Study dates
31 Oct 2018to 31 Dec 2020
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Newly diagnosed histologically confirmed unmethylated glioblastoma multiforme (WHO grade IV). Patients with secondary glioblastoma, in particular those who are IDH1 or IDH2 mutant, will not be excluded. Unmethylated MGMT must be confirmed by a PCR-based assay.
  • Patients who had craniotomy with biopsy, subtotal resection, total gross resection, or re-resection will be permitted.
  • Consented 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:
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  • Absolute neutrophil count ≥ 1,500/mcL
  • Platelets ≥ 100,000/mcL
  • Total bilirubin ≤ 1.5 x institutional upper limit of normal (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).

Who cannot join

  • As this study aims to assess the immunogenicity of various vaccine plus adjuvant combinations, 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.
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  • A history of allergic reactions attributed to compounds of similar chemical or biologic composition to poly-ICLC or other 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 pre-existing immunodeficiency disorder or autoimmune condition requiring 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.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Washington University School of Medicine

    St Louis, Missouri, 63110

Other trials in United States

About this study

Official title: A Pilot Study to Assess the Safety, Feasibility, and Immunogenicity of a Neoantigen-based Personalized Vaccine Combined With Immune Checkpoint Blockade Therapy in Patients With Newly Diagnosed, Unmethylated Glioblastoma

This is a single institution, open-label, multi-arm, pilot study assessing the safety, feasibility, and immunogenicity of a personalized neoantigen-based vaccine plus poly-ICLC (NeoVax) combined with immune checkpoint inhibitors in subjects with newly diagnosed, unmethylated glioblastoma.

Conditions
Glioblastoma
Being tested
NeoVax, Nivolumab, Ipilimumab, Research blood draw, Leukapheresis for research
Medical subject headings
Glioblastoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • NeoVaxBiological

    Also called Synthetic long peptides plus poly-ICLC

    At each vaccination time point, patients will receive up to 20 synthetic long peptides co-administered with 1.5 mg of poly-ICLC divided into a maximum of four injections (pools). Each pool (of vaccine + poly IC:LC) will be administered to one of the four limbs (right axilla, left axilla, right inguina, left inguina) by subcutaneous injection.

  • NivolumabBiological

    Also called Opdivo

    Nivolumab is a programmed death receptor-1 (PD-1) blocking antibody

  • IpilimumabBiological

    Also called Yervoy

    Ipilimumab is a recombinant, human monoclonal antibody that binds to the cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4)

  • Research blood drawProcedure or surgery

    -Baseline, cycle 2 day 1, cycle 4 day 1, and time of progression or discontinuation of treatment

  • Leukapheresis for researchProcedure or surgery

    -Baseline, cycle 4 day 1, and time of progression or discontinuation of treatment

Study groups in NCT03422094
Study groupRoleWhat they receive
Cohort A: NeoVax+Nivolumab (start at time of progression)Experimental* NeoVax given on Days 1, 8, 15, and 22 of Cycle 1 (priming phase), and then on Day 1 of each subsequent cycle (boosting phase) * Nivolumab 480 mg i.v. given on Day 1 of each cycle beginning at time of progression
Receives: Biological: NeoVax; Biological: Nivolumab; Procedure: Research blood draw; Procedure: Leukapheresis for research
Cohort B: NeoVax+Nivolumab (start with Cycle 2)Experimental* NeoVax given on Days 1, 8, 15, and 22 of Cycle 1 (priming phase), and then on Day 1 of each subsequent cycle (boosting phase) * Nivolumab 480 mg i.v. given on Day 1 of each cycle beginning with Cycle 2 (start of boosting phase)
Receives: Biological: NeoVax; Biological: Nivolumab; Procedure: Research blood draw; Procedure: Leukapheresis for research
Cohort C: NeoVax + Nivolumab (start with Cycle 1)Experimental* NeoVax given on Days 1, 8, 15, and 22 of Cycle 1 (priming phase), and then on Day 1 of each subsequent cycle (boosting phase) * Nivolumab 480 mg i.v. given on Day 1 of Cycle 1 (priming phase), and then on Day 1 of each subsequent cycle (boosting phase)
Receives: Biological: NeoVax; Biological: Nivolumab; Procedure: Research blood draw; Procedure: Leukapheresis for research
Cohort D: NeoVax+Ipilimumab+Nivolumab (start with Cycle 3)Experimental* NeoVax given on Days 1, 8, 15, and 22 of Cycle 1 (priming phase), and then on Day 1 of each subsequent cycle (boosting phase) * Ipilimumab 1 mg/kg i.v. given on Days 1 and 22 of Cycle 1 (priming phase) * Nivolumab 480 mg i.v. given on Day 1 of Cycle 3 and then on Day 1 of each subsequent cycle
Receives: Biological: NeoVax; Biological: Nivolumab; Biological: Ipilimumab; Procedure: Research blood draw; Procedure: Leukapheresis for research
Cohort E: NeoVax+Ipilimumab+Nivolumab (day 1&15 each cycle)Experimental* NeoVax given on Days 1, 8, 15, and 22 of Cycle 1 (priming phase), and then on Day 1 of each subsequent cycle (boosting phase) * Ipilimumab 1 mg/kg i.v. given every 6 weeks beginning on Day 1 of Cycle 1 (C1D1, C2D15, C4D1, C5D15, C7D1, C8D15 …) * Nivolumab 3 mg/kg i.v. given on Days 1 and 15 of each cycle (q2w) beginning on Day 1 of Cycle 1
Receives: Biological: NeoVax; Biological: Nivolumab; Biological: Ipilimumab; Procedure: Research blood draw; Procedure: Leukapheresis for research

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Safety and tolerability of regimen as measured by a <= 33% dose-limiting toxicity (DLT) rate for a given cohort

    • The DLT observation period is 60 days after C1D1 for patients enrolled to Cohorts A, C, and D and is 90 days after C1D1 for patients enrolled to Cohorts B and E.
    • DLT is defined as any grade 3 or greater event that occurs during the DLT observation period that is considered at least possibly related to the study treatment.

    Measured: Up to 90 days after start of treatment

  2. Feasibility of generating a personalized neoantigen peptide vaccine as measured by the ability to identify candidate tumor-specific neoantigens

    Measured: From time of resection to 4 weeks post-radiation therapy (approximately 14 weeks)

  3. Feasibility of generating a personalized neoantigen peptide vaccine as measured by the the ability to manufacture a neoantigen-based synthetic long peptide vaccine

    Measured: From time of resection to 4 weeks post-radiation therapy (approximately 14 weeks)

  4. Feasibility of generating a personalized neoantigen peptide vaccine as measured by the ability to administer the vaccine to a patient at 4 weeks post-completion of radiotherapy

    Measured: From time of resection to 4 weeks post-radiation therapy (approximately 14 weeks)

Secondary outcomes (7)

  1. Immunogenicity of a personalized neoantigen peptide vaccine as measured by the ability to generate a measurable neoantigen-specific T cell response in vaccinated patients

    Measured: Week 4 post-vaccination

  2. Immunogenicity of a personalized neoantigen peptide vaccine as measured by the ability to generate a measurable neoantigen-specific T cell response in vaccinated patients

    Measured: Week 16 post-vaccination

  3. Immunogenicity of a personalized neoantigen peptide vaccine as measured by the number of individual neoantigens per number of neoantigens vaccinated against, with which a measurable T cell-specific response

    Measured: Week 4 post-vaccination

  4. Immunogenicity of a personalized neoantigen peptide vaccine as measured by the number of individual neoantigens per number of neoantigens vaccinated against, with which a measurable T cell-specific response

    Measured: Week 16 post-vaccination

  5. Number of high quality candidate neoantigens present in patients with newly diagnosed glioblastoma

    High quality neoantigens will be defined as those that meet criteria for inclusion in a vaccine

    Measured: Up to 2 weeks post sequencing

  6. Progression-free (PFS) survival rate

    Measured: 6 months

  7. Overall survival (OS) rate

    Measured: 12 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted5 Feb 2018
  2. Study start31 Oct 2018
  3. Primary completion26 Apr 2020
  4. Study completion31 Dec 2020

Why it stopped: Manufacturer changed focus to cell therapy

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
3 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03422094
Sponsor's protocol ID
201804195
Status last verified
Oct 2021
First submitted
29 Jan 2018
Last updated
27 Oct 2021
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing NeoVax, Nivolumab and Ipilimumab in people with Glioblastoma, run by Washington University School of Medicine at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 15 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 27 Oct 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: Manufacturer changed focus to cell therapy). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Safety and tolerability of regimen as measured by a <= 33% dose-limiting toxicity (DLT) rate for a given cohort (time frame: Up to 90 days after start of treatment). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03422094.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Oct 2021.

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