- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03422094
Neoantigen-based Personalized Vaccine Combined With Immune Checkpoint Blockade Therapy in Patients With Newly Diagnosed, Unmethylated Glioblastoma
October 26, 2021 updated by: Washington University School of Medicine
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.
Study Overview
Status
Terminated
Conditions
Study Type
Interventional
Enrollment (Actual)
3
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
Genders Eligible for Study
All
Description
Inclusion Criteria:
- 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:
- 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).
Exclusion Criteria:
- 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.
- 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.
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: NON_RANDOMIZED
- Interventional Model: SEQUENTIAL
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: Cohort A: NeoVax+Nivolumab (start at time of progression)
|
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.
Other Names:
Nivolumab is a programmed death receptor-1 (PD-1) blocking antibody
Other Names:
-Baseline, cycle 2 day 1, cycle 4 day 1, and time of progression or discontinuation of treatment
-Baseline, cycle 4 day 1, and time of progression or discontinuation of treatment
|
EXPERIMENTAL: Cohort B: NeoVax+Nivolumab (start with Cycle 2)
|
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.
Other Names:
Nivolumab is a programmed death receptor-1 (PD-1) blocking antibody
Other Names:
-Baseline, cycle 2 day 1, cycle 4 day 1, and time of progression or discontinuation of treatment
-Baseline, cycle 4 day 1, and time of progression or discontinuation of treatment
|
EXPERIMENTAL: Cohort C: NeoVax + Nivolumab (start with Cycle 1)
|
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.
Other Names:
Nivolumab is a programmed death receptor-1 (PD-1) blocking antibody
Other Names:
-Baseline, cycle 2 day 1, cycle 4 day 1, and time of progression or discontinuation of treatment
-Baseline, cycle 4 day 1, and time of progression or discontinuation of treatment
|
EXPERIMENTAL: Cohort D: NeoVax+Ipilimumab+Nivolumab (start with Cycle 3)
|
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.
Other Names:
Nivolumab is a programmed death receptor-1 (PD-1) blocking antibody
Other Names:
-Baseline, cycle 2 day 1, cycle 4 day 1, and time of progression or discontinuation of treatment
-Baseline, cycle 4 day 1, and time of progression or discontinuation of treatment
Ipilimumab is a recombinant, human monoclonal antibody that binds to the cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4)
Other Names:
|
EXPERIMENTAL: Cohort E: NeoVax+Ipilimumab+Nivolumab (day 1&15 each cycle)
|
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.
Other Names:
Nivolumab is a programmed death receptor-1 (PD-1) blocking antibody
Other Names:
-Baseline, cycle 2 day 1, cycle 4 day 1, and time of progression or discontinuation of treatment
-Baseline, cycle 4 day 1, and time of progression or discontinuation of treatment
Ipilimumab is a recombinant, human monoclonal antibody that binds to the cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4)
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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
|
|
Up to 90 days after start of treatment
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Feasibility of generating a personalized neoantigen peptide vaccine as measured by the ability to identify candidate tumor-specific neoantigens
Time Frame: From time of resection to 4 weeks post-radiation therapy (approximately 14 weeks)
|
From time of resection to 4 weeks post-radiation therapy (approximately 14 weeks)
|
|
Feasibility of generating a personalized neoantigen peptide vaccine as measured by the the ability to manufacture a neoantigen-based synthetic long peptide vaccine
Time Frame: From time of resection to 4 weeks post-radiation therapy (approximately 14 weeks)
|
From time of resection to 4 weeks post-radiation therapy (approximately 14 weeks)
|
|
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
Time Frame: From time of resection to 4 weeks post-radiation therapy (approximately 14 weeks)
|
From time of resection to 4 weeks post-radiation therapy (approximately 14 weeks)
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Immunogenicity of a personalized neoantigen peptide vaccine as measured by the ability to generate a measurable neoantigen-specific T cell response in vaccinated patients
Time Frame: Week 4 post-vaccination
|
Week 4 post-vaccination
|
|
Immunogenicity of a personalized neoantigen peptide vaccine as measured by the ability to generate a measurable neoantigen-specific T cell response in vaccinated patients
Time Frame: Week 16 post-vaccination
|
Week 16 post-vaccination
|
|
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
Time Frame: Week 4 post-vaccination
|
Week 4 post-vaccination
|
|
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
Time Frame: Week 16 post-vaccination
|
Week 16 post-vaccination
|
|
Number of high quality candidate neoantigens present in patients with newly diagnosed glioblastoma
Time Frame: Up to 2 weeks post sequencing
|
High quality neoantigens will be defined as those that meet criteria for inclusion in a vaccine
|
Up to 2 weeks post sequencing
|
Progression-free (PFS) survival rate
Time Frame: 6 months
|
6 months
|
|
Overall survival (OS) rate
Time Frame: 12 months
|
12 months
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Collaborators
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)
October 31, 2018
Primary Completion (ACTUAL)
April 26, 2020
Study Completion (ACTUAL)
December 31, 2020
Study Registration Dates
First Submitted
January 29, 2018
First Submitted That Met QC Criteria
January 29, 2018
First Posted (ACTUAL)
February 5, 2018
Study Record Updates
Last Update Posted (ACTUAL)
October 27, 2021
Last Update Submitted That Met QC Criteria
October 26, 2021
Last Verified
October 1, 2021
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
- Molecular Mechanisms of Pharmacological Action
- Antineoplastic Agents
- Immunologic Factors
- Antineoplastic Agents, Immunological
- Immune Checkpoint Inhibitors
- Interferon Inducers
- Nivolumab
- Poly ICLC
- Ipilimumab
Other Study ID Numbers
- 201804195
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
No
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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