Nivolumab in Patients With IDH-Mutant Gliomas With and Without Hypermutator Phenotype

NCT03718767 | Active Not Recruiting Phase 2 Results FDA Drug

• 2 other identifiers: 19000619-C-0006
• Study Type: interventional
• Target: 62
• Locations: 1 country
• Sites: 1

Brief Summary

Background: Gliomas are the most common malignant brain tumors. Some have certain changes (mutations) in the genes isocitrate dehydrogenase 1 (IDH1) or isocitrate dehydrogenase 2 (IDH2). If there are a high number of mutations in a tumor, it is called hypermutator phenotype (HMP). The drug nivolumab helps the immune system fight cancer. Researchers think it can be more effective in patients with IDH1 or IDH2 mutated gliomas with HMP. They will test gliomas with and without HMP. Objectives: To see if nivolumab stops tumor growth and prolongs the time that the tumor is controlled. Eligibility: Adults 18 years or older with IDH1 or IDH2 mutated gliomas Design: Participants will be screened with: Medical history Physical exam Heart, blood, and pregnancy tests Review of symptoms and activity levels Brain magnetic resonance imaging (MRI). Participants will lie in a cylinder that takes pictures in a strong magnetic field. Tumor samples Participants will get the study drug in 4-week cycles. They will get it through a small plastic tube in a vein (intravenous \[IV\]) on days 1 and 15 of cycles 1-4. For cycles 5-16, they will get it just on day 1. On days 1 and 15 of each cycle, participants will repeat some or all screening tests. After cycle 16, participants will have 3 follow-up visits over 100 days. They will answer health questions, have physical and neurological exams, and have blood tests. They may have a brain MRI. Participants whose disease did not get worse but who finished the study drug within 1 year of treatment may have imaging studies every 8 weeks for up to 1 year. Participants will be called or emailed every 6 months with questions about their health.

Conditions

Glioma; Glioblastoma; High Grade Glioma; Low Grade Glioma; Malignant Glioma

Keywords

PD 1 Pathway; High Tumor Mutational Load; Immune Checkpoint; Quality of Life

Outcome Measures

Primary Outcomes (1)

• Median Progression Free Survival (PFS) Rate at 6 Months

  PFS is defined from the day of study entry until imaging is confirmed to show disease progression or death, whichever occurs first. Disease progression was assessed by the Immunotherapy Response Assessment neuro-oncology Criteria. Disease progression is \>25% increase in sum of the products of perpendicular diameters of enhancing lesions; any new enhancing measurable lesion that exceeds a 25% increase in cross-sectional area; clear clinical deterioration not attributable to other causes apart from the tumor and/or failure to return for evaluation due to death or deteriorating condition. PFS was analyzed by the Kaplan-Meier method and is reported with a 95% confidence interval.

  6 months

Secondary Outcomes (7)

• Mean Symptom Interference Score Per Treatment Cycle Using the MD Anderson Symptom Inventory-Brain Tumor Module (MDSAI-BT)

  Baseline and Cycles 2, 4, 6, 8, 10, 12, 14, and 16 (approximately 32 weeks +/- 3 days).

• Mean Symptom Severity Score Per Treatment Cycle Using the MD Anderson Symptom Inventory-Brain Tumor Module (MDSAI-BT)

  Baseline and Cycles 2, 4, 6, 8, 10, 12, 14, and 16 (approximately 32 weeks +/- 3 days).

• Overall Survival

  Until the death of the last surviving participant, a median of 7.4 months in Cohort 1 and a median of 31.6 months in Cohort 2.

• Tumor Mutation Burden

  During the screening period (14 days prior to study therapy)

• Proportion of Participants Rating Symptoms 5 or Greater (on a 0-10 Scale) Using the MD Anderson Symptom Inventory-Brain Tumor Module (MDSAI-BT)

  Baseline and Cycles 2, 4, 6, 8, 10, 12, 14, and 16 (approximately 32 weeks +/- 3 days).

Other Outcomes (1)

• Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0)

  From the first study intervention, Study Day 1 of Cycle 1 through 30 days after the study agent (s) was/were administered, up to 17 months

Study Arms (1)

Arm1/Nivolumab

EXPERIMENTAL

Intravenous (IV) nivolumab

Drug: Nivolumab

Interventions

Nivolumab DRUG

Intravenous (IV) Nivolumab

Also known as: Opdivo

Arm1/Nivolumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have recurrent diffuse glioma (histologically confirmed by National Institutes of Health (NIH) Laboratory of Pathology) with isocitrate dehydrogenase 1 (IDH1) or isocitrate dehydrogenase 2 (IDH2) mutation (confirmed by deoxyribonucleic acid (DNA) sequencing, Foundation One is preferable for confirmation of mutation, but not necessary).
• Patients must have tumor specific mutation burden (number of somatic mutations per exome) tested at NIH: Must have either result of tumor mutation burden from the most recent surgical tumor sample or must provide adequate genomic materials of the sample for tumor testing. The tumor tissue (e.g., block or 15 unstained slides) must be available for molecular and immune profiling. Fresh or frozen tumor sample will be used if available, but not mandatory.
• Age greater than or equal to 18 years. Because no dosing or adverse event data are currently available on the use of nivolumab in patients \<18 years of age, children are excluded from this study but will be eligible for future pediatric trials.
• Patient must be able to tolerate a magnetic resonance imaging (MRI) study with intravenous gadolinium contrast.
• Karnofsky greater than or equal to 60%
• Patients must have adequate organ and marrow function as defined below:
• Absolute neutrophil count greater than or equal to 1,500/mcL
• Platelet Count greater than or equal to 100,000/MCL
• Hemoglobin greater than 9.0 g/dL (may be transfused to achieve this level)
• Blood Urea Nitrogen (BUN) less than or equal to 30 mg/dL and
• Serum creatinine less than or equal to 1.7 mg/dL
• Total bilirubin (except patients with Gilbert's Syndrome, who are eligible for the study but exempt from the total bilirubin eligibility criterion) less than or equal to 2.0 mg/dL
• Alanine aminotransferase (ALT) and aspartate aminotransaminase (AST) less than or equal to 2.5x institutional upper limit of normal.
• The effects of nivolumab on the developing human fetus are unknown. For this reason, women of child-bearing potential 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 and up to 5 months (women). Should a woman become pregnant or suspect she is pregnant while she is participating in this study, she should inform her treating physician immediately.
• The patient must be able to understand and be willing to sign a written informed consent document.

You may not qualify if:

• Patients who are receiving any other investigational agents.
• Patients who have a history of receiving immune therapy.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to nivolumab.
• History of severe hypersensitivity reaction to any monoclonal antibody.
• Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 3 years prior to initiation of study therapy.
• Patients with active autoimmune disease or history of autoimmune disease that might recur, which may affect vital organ function or require immune suppressive treatment including systemic corticosteroids. These include but are not limited to patients with a history of immune related neurologic disease, multiple sclerosis, autoimmune (demyelinating) neuropathy, Guillain-Barre syndrome or Chronic Inflammatory Demyelinating Polyneuropathy (CIDP), myasthenia gravis; systemic autoimmune disease such as Systemic Lupus Erythematosus (SLE), connective tissue diseases, scleroderma, inflammatory bowel disease (IBD), Crohn's, ulcerative colitis, hepatitis; and patients with a history of toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome, or phospholipid syndrome. Such diseases should be excluded because of the risk of recurrence or exacerbation of disease.
• Of note, patients with vitiligo, endocrine deficiencies including thyroiditis managed with replacement hormones including physiologic corticosteroids are eligible. Patients with rheumatoid arthritis and other arthropathies, Sjogren's syndrome and psoriasis controlled with topical medication and patients with positive serology, such as antinuclear antibodies (ANA), anti-thyroid antibodies should be evaluated for the presence of target organ involvement and potential need for systemic treatment but should otherwise be eligible.
• The patient must not be currently on a corticosteroid dose greater than dexamethasone 1 mg per day or its equivalent.
• 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 (within timeframes identified in the bullets below) that would limit compliance with study requirements.
• Known human immunodeficiency virus (HIV)-positive or acquired immune deficiency syndrome (AIDS) based upon current Centers for Disease Control and Prevention (CDC) definition; note, however, that HIV testing is not required for entry into this protocol. The need to exclude patients with AIDS is based on the lack of information regarding the safety of nivolumab in patients with active HIV infection
• Pregnant women are excluded from this study because nivolumab's potential for teratogenic or abortifacient effects is unknown. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with nivolumab, breastfeeding should be discontinued if the mother is treated with nivolumab.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Glioma; Glioblastoma

Interventions

Nivolumab

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Astrocytoma

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Dr. Jing Wu
• Organization: National Cancer Institute

jing.wu3@nih.gov

240-760-6036

Study Officials

• Jing Wu, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: October 23, 2018
• First Posted: October 24, 2018
• Study Start: March 27, 2019
• Primary Completion: November 5, 2024
• Study Completion (Estimated): November 30, 2026
• Last Updated: November 24, 2025
• Results First Posted: November 24, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Biomedical Translational Research Information System (BTRIS): Clinical data available during the study and indefinitely. The database of Genotypes and Phenotypes (dbGaP): Genomic data are available once genomic data are uploaded per protocol Genomic Data Sharing (GDS) plan for as long as database is active.
• Access Criteria: Biomedical Translational Research Information System (BTRIS): Clinical data will be made available via subscription to BTRIS and with the permission of the study principal investigator (PI). The database of Genotypes and Phenotypes (dbGaP): Genomic data are made available via dbGaP through requests to the data custodians.

Locations

US (1)