Association of Peripheral Blood Immunologic Response to Therapeutic Response to Adjuvant Treatment With Immune Checkpoint Inhibition (ICI) in Patients With Newly Diagnosed Glioblastoma or Gliosarcoma

NCT04817254 | Completed Phase 2 FDA Drug

• 2 other identifiers: 21001521-C-0015
• Study Type: interventional
• Target: 47
• Locations: 1 country
• Sites: 1

Brief Summary

Background: Glioblastoma (GBM) is a type of malignant glioma. These cancers are nearly always fatal. People who develop these cancers get aggressive treatments. But the tumors almost always recur. Researchers want to study people with newly diagnosed disease to learn more. Objective: To study people with newly diagnosed GBM or gliosarcoma to look at the changes in immune cells in the blood of those who take ipilimumab and nivolumab, along with temozolomide. Eligibility: Adults ages 18 and older with newly diagnosed GBM or gliosarcoma, who have had surgical removal of their tumor and have completed standard initial chemotherapy and radiation therapy. Design: Participants will be screened with the following: Medical record review Medical history Physical exam Tests to assess their nervous system and their ability to do typical activities Blood tests Tumor assessment. For this, they will have magnetic resonance imaging (MRI). They may get a contrast dye through an intravenous (IV) catheter. The MRI scanner makes noise. They will get earplugs. Electrocardiogram. It measures heart rate and rhythm. They will lie still. Sticky pads will be placed on their chest, arms, and legs. Screening tests will be repeated during the study. Treatment will be given in cycles. Each cycle lasts 4 weeks. Participants will get nivolumab and ipilimumab via IV. They will take temozolomide by mouth. They will keep a pill diary. Participants will fill out surveys about their symptoms. Participants will have follow-up visits about 60 days and 100 days after treatment ends. Then they will be contacted every 6 months for the rest of their life.

Conditions

Glioblastoma; Gliosarcoma; Malignant Glioma

Keywords

Brain Cancer; Quality of Life

Outcome Measures

Primary Outcomes (1)

• Determine if the outcomes, as measured by overall survival, is improved in patients with newly diagnosed glioblastoma when treatment with immune checkpoint inhibitors result in an immune response in peripheral blood T lymphocytes.

  Correlation between the Median amount of time subject survives after therapy and quantitative analysis of peripheral blood T lymphocytes.

  death

Secondary Outcomes (5)

• Determine if the T cell response measured by the ex vivo tosylactivated bead assay correlates with subsequent systemic response to treatment with immune checkpoint inhibitors.

  Baseline, Day 1 of each Cycle and 60 day and 100 day post treatment

• Determine if T cell response to immune checkpoint inhibitors measuring the change in the pre-treatment and post-treatment blood correlates with progression-free survival

  disease progression

• Determine if in vitro peripheral blood T cell response to a stimulation paradigm including nivolumab and ipilimumab correlates with progression-free survival, evaluating 2 different dosing regimens of the ICIs.

  disease progression

• Determine if in vitro peripheral blood T cell response to a stimulation paradigm including nivolumab and ipilimumab correlates with overall survival, evaluating 2 different dosing regimens of the ICIs.

  death

• Evaluate changes in patient reported outcome measures using self-reported symptom severity and interference with daily activities using the MDASI-BT with treatment response and progression-free and overall survival.

  Study Calendar, last collection of QOL Questioner

Study Arms (2)

Arm 1

EXPERIMENTAL

Nivolumab + Ipilimumab 1mg/kg + TMZ

Drug: TMZ; Drug: Nivolumab; Drug: ipilimumab 1mg/kg

Arm 2

EXPERIMENTAL

Nivolumab + Ipilimumab 3mg/kg + TMZ

Drug: TMZ; Drug: ipilimumab 3mg/kg; Drug: Nivolumab

Interventions

TMZ DRUG

150 mg/m2 on days 1-5 of cycles 1-6

Arm 1; Arm 2

ipilimumab 3mg/kg DRUG

3 mg/kg q 4 weeks for cycles 1-4

Arm 2

Nivolumab DRUG

1 mg/kg IV q2weeks for cycles 1-4, then 480 mg q 4 weeks for cycles 5-16

Arm 1; Arm 2

ipilimumab 1mg/kg DRUG

1 mg/kg q 4 weeks for cycles 1-4

Arm 1

Eligibility Criteria

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

You may qualify if:

• Participants must have newly diagnosed histologically confirmed primary glioblastoma or gliosarcoma
• Participants must have undergone an extensive resection of unifocal, confined to the supratentorial compartment, tumor.
• Participant must have completed chemoradiation (external beam radiation with concurrent temozolomide) a maximum of 5 weeks prior to initiation of study therapy. Potential participants who have a limited short term, reversable, unrelated to their underlying disease, concurrent illness, the initiation of treatment may be delayed up to 14 days, if the participant meet all other I/E criteria at that time.
• Age greater than or equal to 18 years.
• Karnofsky greater than or equal to 70%
• Participants must have adequate organ and marrow function as defined below:
• Absolute neutrophil count greater than or equal to 1,500/mcL
• Platelet Count \>100,000/mcL
• Hemoglobin \> 9.0 g/dL (may be transfused to achieve this level)
• BUN less than or equal to 30 mg/dL
• Serum creatinine less than or equal to 1.7 mg/dL or creatinine clearance as measured by 24 hour urine collection as \> 60 ml/min.
• Total bilirubin (except participants 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 study treatment on the developing human fetus are unknown. For this reason, participants of reproductive potential must agree to abstinence or use adequate contraception which includes a combination of TWO of the following:
• Barrier method of contraception: condoms (male or female) with or without a spermicidal agent, diaphragm, or cervical cap with spermicide

You may not qualify if:

• Definitive clinical or radiologic evidence of progressive disease.
• Prior placement of Gliadel wafer or local brachytherapy. Note: Tumor Treating Fields are allowed.
• Participants who are receiving any other investigational agents.
• Participants who have a history of receiving immune therapy, such as a vaccine therapy, dendritic cell vaccine or intracavitary or convectional enhanced delivery of therapy.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to nivolumab, ipilimumab or temozolomide.
• History of allergic reactions attributed to gadolinium contrast.
• History of severe hypersensitivity reaction to any monoclonal antibody.
• Prior or concurrent malignancy unless its natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen.
• Participants 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 participants 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, and hepatitis; and participants 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.
• Note: Participants with vitiligo, endocrine deficiencies including thyroiditis managed with replacement hormones including physiologic corticosteroids are eligible. Participants with rheumatoid arthritis and other arthropathies, Sjogren s syndrome, psoriasis controlled with topical medication, and participants with positive serology, such as antinuclear antibodies (ANA) and 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 participant must not be currently on a corticosteroid dose greater than physiologic replacement dosing defined as 30 mg of cortisone per day or its equivalent. Participants must have stopped corticosteroids above this threshold at least 7 days prior to initiation of study treatment.
• 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.
• Individual who are pregnant are excluded from this study because study treatment potential for teratogenic or abortifacient effects is unknown. Because there is an unknown but potential risk for adverse events in nursing infants secondary to study treatment of the mother, breastfeeding should be discontinued.

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

Glioblastoma; Gliosarcoma; Glioma; Brain Neoplasms

Interventions

Ipilimumab; Nivolumab

Condition Hierarchy (Ancestors)

Astrocytoma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

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

Study Officials

• Kevin A Camphausen, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 25, 2021
• First Posted: March 26, 2021
• Study Start: December 8, 2021
• Primary Completion: March 20, 2026
• Study Completion: March 20, 2026
• Last Updated: April 17, 2026

Record last verified: 2026-04-15

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: BTRIS: Clinical data available during the study and indefinitely.@@@@@@All collected IPD will be available after primary analysis have been published.
• Access Criteria: BTRIS: Clinical data will be made available via subscription to BTRIS and with the permission of the study PI.

Locations

US (1)