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

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ClinicalTrials.gov Identifier: NCT03718767
Recruitment Status : Recruiting
First Posted : October 24, 2018
Last Update Posted : September 28, 2022
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )

Brief Summary:


Gliomas are the most common malignant brain tumors. Some have certain changes (mutations) in the genes IDH1 or 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.


To see if nivolumab stops tumor growth and prolongs the time that the tumor is controlled.


Adults 18 years or older with IDH1 or IDH2 mutated gliomas


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 (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.


Condition or disease Intervention/treatment Phase
Glioma Glioblastoma High Grage Glioma Low Grade Glioma Malignant Glioma Drug: Nivolumab Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 95 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Trial Evaluating Nivolumab In Patients With IDH-Mutant Gliomas With And Without Hypermutator Phenotype
Actual Study Start Date : March 27, 2019
Estimated Primary Completion Date : September 30, 2025
Estimated Study Completion Date : February 27, 2026

Resource links provided by the National Library of Medicine

Drug Information available for: Nivolumab

Arm Intervention/treatment
Experimental: 1/Nivolumab
IV nivolumab
Drug: Nivolumab
IV Nivolumab

Primary Outcome Measures :
  1. 6-month progression free survival rate [ Time Frame: 6 months ]
    Proportion of patients that do not have progressive disease after 6 months

Secondary Outcome Measures :
  1. Proportion of patients that have improvement in quality of life [ Time Frame: Study Calendar -last collection of QOL questioner. ]
    To longitudinally evaluate patient reported outcome measures using self-reported symptom severity and interference with daily activities using the MDASI-BT.

  2. Median amount of time subject survives after therapy and Proportion of patients that have progressive disease after 12 months [ Time Frame: 12 months and death ]
    To determine the 1-year progression free survival rate and overall survival in IDH-mutant gliomas patients with and without HMP in response to nivolumab treatment.

  3. Correlation between neoantigen burden of tumor and proportion of subjects that survive after 6 and 12 months [ Time Frame: 6 months and 12 months ]
    To determine whether the neoantigen burden in tumor prior to the treatment is correlated with treatment response.

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
  • Patients must have recurrent diffuse glioma (histologically confirmed by NIH Laboratory of Pathology) with IDH1 or IDH2 mutation (confirmed by DNA sequencing, FoundationOne 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 olecular 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 an 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)
    • 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
    • ALT and 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.


  • 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 CIDP, myasthenia gravis; systemic autoimmune disease such as 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, Sj(SqrRoot)(Delta)gren 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 HIV-positive or acquired immune deficiency syndrome (AIDS) based upon current 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.
  • Known active, chronic or history of hepatitis infection.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03718767

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Contact: NCI NOB Referral Group (866) 251-9686 ncinobreferrals@mail.nih.gov
Contact: Jing Wu, M.D. (240) 760-6036 jing.wu3@nih.gov

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United States, Maryland
National Institutes of Health Clinical Center Recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact National Cancer Institute Referral Office    888-624-1937      
Sponsors and Collaborators
National Cancer Institute (NCI)
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Principal Investigator: Jing Wu, M.D. National Cancer Institute (NCI)
Additional Information:
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Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT03718767    
Other Study ID Numbers: 190006
First Posted: October 24, 2018    Key Record Dates
Last Update Posted: September 28, 2022
Last Verified: July 27, 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: .BTRIS: All IPD recorded in the medical record will be shared with intramural investigators upon request.@@@@@@dbGaP: All large scale genomic sequencing data will be shared with subscribers to dbGaP.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Time Frame: BTRIS: Clinical data available during the study and indefinitely.@@@@@@dbGaP: Genomic data are available once genomic data are uploaded per protocol GDS plan for as long as database is active.
Access Criteria: BTRIS: Clinical data will be made available via subscription to BTRIS and with the permission of the study PI. @@@@@@dbGaP: Genomic data are made available via dbGaP through requests to the data custodians.

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) ):
PD 1 Pathway
High Tumor Mutational Load
Immune Checkpoint
Quality of Life
Additional relevant MeSH terms:
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Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immune Checkpoint Inhibitors
Molecular Mechanisms of Pharmacological Action