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
- Conditions
- Malignant GliomaGlioblastomaGliosarcoma
- Interventions
- Registration Number
- NCT04817254
- Lead Sponsor
- National Cancer Institute (NCI)
- 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.
- Detailed Description
Background:
Glioblastoma (GBM) represents an aggressive malignancy with limited therapeutic options. The immunosuppressive nature of GBM may be reversible with immune checkpoint inhibitor (ICI) treatment, however, initial studies have yet to demonstrate this. It is postulated that trafficking of peripherally activated lymphocytes may play a role in generating a robust intracranial immune response. Therefore, a blood-based assay to identify peripheral blood response may both predict response and better identify the ideal patient populations for future ICI clinical trials.
Objectives:
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.
Eligibility:
Histologically confirmed, newly diagnosed primary glioblastoma or gliosarcoma;
Age greater than or equal to 18 years;
Adequate organ function;
Karnofsky performance score greater than or equal to 70;
Subjects must recently complete resection and chemoradiation;
Subjects must not have prior immunotherapy, other current investigational agents, or corticosteroid treatment \> 30mg cortisone-equivalents per day.
Design:
Open-label, investigator-initiated exploratory study of newly-diagnosed GBM who have completed resection and chemoradiation.
Participants will be randomized to be treated in Arm 1 or 2, consistent of adjuvant chemotherapy (temozolomide (TMZ)) and immunotherapy (nivolumab + ipilimumab):
TMZ (150-200 mg/m2 PO on days 1-5 q28 days for cycles 1-6)
Arm 1:
Nivolumab (1 mg/kg IV q2weeks for cycles 1-4, then 480 mg IV q4weeks for cycles 5-16) + ipilimumab (1 mg/kg IV q4 weeks for cycles 1-4)
Arm 2:
Nivolumab (1 mg/kg IV q2weeks for cycles 1-4, then 480 mg IV q4weeks for cycles 5-16) + ipilimumab (3 mg/kg IV q4 weeks for cycles 1-4)
For the primary objective, serial examination of peripheral blood, including comprehensive flow cytometric analysis of leukocyte populations and cytokines, and Interferon- \>= (IFN- \>=) ELISPOT functional analysis of CD4+/8+ response to common recall antigens will be used to determine systemic response to ICI treatment.
For the secondary objectives, correlative studies assess peripheral blood T cells' ability to respond to an in vitro stimulation paradigm, including nivolumab and ipilimumab, in a microbead-based model. The T cell response to pretreatment in vitro stimulation would be compared to post-treatment in vivo stimulation to determine if this in vitro model can predict in vivo response.
Additional exploratory studies are planned to characterize the in vivo immune response to adjuvant chemotherapy and immunotherapy, including but not limited to:
Phospho-flow functional analysis of NK cell response to IFN/IL-15 stimulation.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 47
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm 1 ipilimumab 1mg/kg Nivolumab + Ipilimumab 1mg/kg + TMZ Arm 2 ipilimumab 3mg/kg Nivolumab + Ipilimumab 3mg/kg + TMZ Arm 1 TMZ Nivolumab + Ipilimumab 1mg/kg + TMZ Arm 1 Nivolumab Nivolumab + Ipilimumab 1mg/kg + TMZ Arm 2 TMZ Nivolumab + Ipilimumab 3mg/kg + TMZ Arm 2 Nivolumab Nivolumab + Ipilimumab 3mg/kg + TMZ
- Primary Outcome Measures
Name Time Method 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. death Correlation between the Median amount of time subject survives after therapy and quantitative analysis of peripheral blood T lymphocytes.
- Secondary Outcome Measures
Name Time Method 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 Correlation between T cell response with varying dose regimen of immune checkpoint inhibitors and 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 Correlation between T cell response with varying dose regimen of immune checkpoint inhibitors and death
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 Measurement of pretreatment and posttreatment blood correlates and its correlation T cell response to checkpoint inhibitors.
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 Proportion of patients that have an improvement in quality of life
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 Correlation between T cell response to immune checkpoint inhibitors and survival
Trial Locations
- Locations (1)
National Institutes of Health Clinical Center
🇺🇸Bethesda, Maryland, United States