RECRUITING

Study to Evaluate Safety, Tolerability, and Optimal Dose of Candidate GBM Vaccine VBI-1901 in Recurrent GBM Subjects

Conditions

Glioblastoma Multiforme GBM Glioblastoma eVLP VBI-1901 vaccine immunotherapy CMV CNS Brain Cancer

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

The purpose of this study is to assess the safety and tolerability of VBI-1901 in subjects with recurrent malignant gliomas (glioblastoma, or GBM).

Official Title

A Three-part, Phase I/II Dose-Escalation Study to Define the Safety, Tolerability, and Optimal Dose of Candidate GBM Vaccine VBI-1901 With Subsequent Extension of Optimal Dose in Recurrent GBM Subjects

Quick Facts

Study Start:2017-12-06

Study Completion:2025-08

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT03382977

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.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
1. 18-70 years of age 2. Histologically confirmed WHO grade IV glioblastoma 3. Unequivocal evidence of a tumor recurrence (any number of recurrences) or progression after an initial treatment regimen (prior to enrollment on this study) as assessed by MRI of the brain with and without contrast within 30 days prior to the initiation of injections of VBI-1901. An initial therapy requires surgery and radiation therapy, with or without temozolomide. In addition, alternate therapy (with or instead of temozolomide) is permitted as part of initial therapy. 4. Recovery from the effects of surgery. 5. Corticosteroid (dexamethasone or equivalent) dosage ≤ 4mg daily that has been stable or decreasing for at least 5 days. 6. Recovery from prior therapy toxicity defined as resolution of all treatment-related adverse events (AEs) to Grade ≤ 1 or pre-treatment baseline (except alopecia). 7. Karnofsky performance status (KPS) score ≥ 70%. 8. Adequate organ function, including the following: 1. Absolute neutrophil count (ANC) ≥ 1,000/μL, platelets ≥ 100,000/μL 2. Serum creatinine \< 1.5 × the upper limit of normal (ULN) 3. Bilirubin \< 1.5 × ULN 4. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) \< 2.5 × ULN 9. Women of childbearing potential: negative urine pregnancy test within 14 days prior to the start of VBI-1901 treatment. 10. Female subjects of childbearing potential and sexually active male subjects must agree to use an acceptable form of contraception for heterosexual activity (i.e., oral contraceptives, double barrier methods, hormonal injectable, transdermal, or implanted contraceptives, tubal ligation, or vasectomy of their sexual partner(s) for \>30 days before Screening, during the study, and for 60 days after the last dose of study drug). 11. Female subjects without childbearing potential (spontaneous amenorrhea for \> 12 months or surgically sterilized by tubal ligation, hysterectomy, or bilateral oophorectomy \> 6 months before Screening) are eligible for inclusion without contraceptive use restriction. 12. Able and willing to comply with protocol requirements in the opinion of the Investigator, including being able to have an MRI. 13. Written consent has been obtained. 14. Tumor specimen available for central pathological review.	1. Contrast-enhancing residual tumor that is associated with either diffuse sub-ependymal or leptomeningeal dissemination. 2. Requirement of systemic corticosteroid therapy \> 4 mg/day of dexamethasone or equivalent or requirement of increasing dose of systemic corticosteroids during the 7 days prior to the start of VBI-1901 treatment. 3. Evidence of HCMV viremia in serum of \> 18,200 (4.3Log10) IU/mL using FDA approved COBAS® AmpliPrep/COBAS® TaqMan® HCMV test (Roche). 4. Surgical resection or major surgical procedure within 4 days prior to the start of VBI-1901, or stereotactic biopsy within 7 days prior to the start of VBI-1901. 5. Active infection requiring intravenous antibiotics or antiviral. 6. History of cancer (other than GBM or prostate) within the past 2 years that could negatively impact survival and/or potentially confound tumor response assessments within this study. 7. Known immunosuppressive disease or active systemic autoimmune disease such as systemic lupus erythematosus, human immunodeficiency virus infection, Hepatitis B virus or Hepatitis C virus infections. Subjects with vitiligo, type 1 diabetes mellitus, hypothyroidism due to autoimmune condition only requiring hormone replacement therapy, psoriasis not requiring systemic therapy, or conditions not expected to recur in the absence of an external trigger are permitted to enroll. 8. Immunosuppressive agent within 4 weeks prior to the start of VBI-1901 treatment. 9. Evidence of intra-tumoral or peri-tumoral hemorrhage on baseline, other than those that are ≤Grade 1 and either post-operative or stable on at least 2 consecutive MRI scans. 10. Any condition which in the investigator's opinion makes the subject unsuitable for study participation. 11. Lack of family or social support structure that would preclude continued participation in the study.

Inclusion Criteria

Exclusion Criteria

1. 18-70 years of age
2. Histologically confirmed WHO grade IV glioblastoma
3. Unequivocal evidence of a tumor recurrence (any number of recurrences) or progression after an initial treatment regimen (prior to enrollment on this study) as assessed by MRI of the brain with and without contrast within 30 days prior to the initiation of injections of VBI-1901. An initial therapy requires surgery and radiation therapy, with or without temozolomide. In addition, alternate therapy (with or instead of temozolomide) is permitted as part of initial therapy.
4. Recovery from the effects of surgery.
5. Corticosteroid (dexamethasone or equivalent) dosage ≤ 4mg daily that has been stable or decreasing for at least 5 days.
6. Recovery from prior therapy toxicity defined as resolution of all treatment-related adverse events (AEs) to Grade ≤ 1 or pre-treatment baseline (except alopecia).
7. Karnofsky performance status (KPS) score ≥ 70%.
8. Adequate organ function, including the following:
1. Absolute neutrophil count (ANC) ≥ 1,000/μL, platelets ≥ 100,000/μL
2. Serum creatinine \< 1.5 × the upper limit of normal (ULN)
3. Bilirubin \< 1.5 × ULN
4. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) \< 2.5 × ULN
9. Women of childbearing potential: negative urine pregnancy test within 14 days prior to the start of VBI-1901 treatment.
10. Female subjects of childbearing potential and sexually active male subjects must agree to use an acceptable form of contraception for heterosexual activity (i.e., oral contraceptives, double barrier methods, hormonal injectable, transdermal, or implanted contraceptives, tubal ligation, or vasectomy of their sexual partner(s) for \>30 days before Screening, during the study, and for 60 days after the last dose of study drug).
11. Female subjects without childbearing potential (spontaneous amenorrhea for \> 12 months or surgically sterilized by tubal ligation, hysterectomy, or bilateral oophorectomy \> 6 months before Screening) are eligible for inclusion without contraceptive use restriction.
12. Able and willing to comply with protocol requirements in the opinion of the Investigator, including being able to have an MRI.
13. Written consent has been obtained.
14. Tumor specimen available for central pathological review.

1. Contrast-enhancing residual tumor that is associated with either diffuse sub-ependymal or leptomeningeal dissemination.
2. Requirement of systemic corticosteroid therapy \> 4 mg/day of dexamethasone or equivalent or requirement of increasing dose of systemic corticosteroids during the 7 days prior to the start of VBI-1901 treatment.
3. Evidence of HCMV viremia in serum of \> 18,200 (4.3Log10) IU/mL using FDA approved COBAS® AmpliPrep/COBAS® TaqMan® HCMV test (Roche).
4. Surgical resection or major surgical procedure within 4 days prior to the start of VBI-1901, or stereotactic biopsy within 7 days prior to the start of VBI-1901.
5. Active infection requiring intravenous antibiotics or antiviral.
6. History of cancer (other than GBM or prostate) within the past 2 years that could negatively impact survival and/or potentially confound tumor response assessments within this study.
7. Known immunosuppressive disease or active systemic autoimmune disease such as systemic lupus erythematosus, human immunodeficiency virus infection, Hepatitis B virus or Hepatitis C virus infections. Subjects with vitiligo, type 1 diabetes mellitus, hypothyroidism due to autoimmune condition only requiring hormone replacement therapy, psoriasis not requiring systemic therapy, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
8. Immunosuppressive agent within 4 weeks prior to the start of VBI-1901 treatment.
9. Evidence of intra-tumoral or peri-tumoral hemorrhage on baseline, other than those that are ≤Grade 1 and either post-operative or stable on at least 2 consecutive MRI scans.
10. Any condition which in the investigator's opinion makes the subject unsuitable for study participation.
11. Lack of family or social support structure that would preclude continued participation in the study.

Contacts and Locations

Study Contact

Bebi Yassin-Rajkumar, MS

CONTACT

866-574-7034

BYassin-Rajkumar@vbivaccines.com

Principal Investigator

Francisco Diaz-Mitoma, MD

STUDY_DIRECTOR

Variation Biotechnologies Inc.

Study Locations (Sites)

University of California, Irvine

Irvine, California, 92868

United States

University of California, San Diego

La Jolla, California, 92093

United States

University of California, Los Angeles Neuro-Oncology Program

Los Angeles, California, 90095

United States

Stanford

Stanford, California, 94305

United States

Miami Cancer Institute

Miami, Florida, 33176

United States

Massachusetts General Hospital

Boston, Massachusetts, 02114

United States

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215

United States

The Valley Hospital - Neurosurgeons of New Jersey

Ridgewood, New Jersey, 07450

United States

The Neurological Institute of New York Columbia University Medical Center

New York, New York, 10032

United States

Vanderbilt University Medical Center

Nashville, Tennessee, 37232

United States

MD Anderson Cancer Center

Houston, Texas, 77030

United States

Providence - Swedish Medical Center

Seattle, Washington, 98122

United States

Collaborators and Investigators

Sponsor: VBI Vaccines Inc.

Francisco Diaz-Mitoma, MD, STUDY_DIRECTOR, Variation Biotechnologies Inc.

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 Registration Dates

Study Start Date2017-12-06

Study Completion Date2025-08

Study Record Updates

Study Start Date2017-12-06

Study Completion Date2025-08

Terms related to this study

Keywords Provided by Researchers

GBM
Glioblastoma
eVLP
VBI-1901
vaccine
immunotherapy
CMV
CNS
Brain
Cancer

Additional Relevant MeSH Terms

Glioblastoma Multiforme