Anti-Lag-3 (Relatlimab) and Anti-PD-1 Blockade (Nivolumab) Versus Standard of Care (Lomustine) for the Treatment of Patients With Recurrent Glioblastoma
Study Purpose
This phase II trial compares the safety, side effects and effectiveness of anti-lag-3 (relatlimab) and anti-PD-1 blockade (nivolumab) to standard of care lomustine for the treatment of patients with glioblastoma that has come back after a period of improvement (recurrent). Relatlimab and nivolumab are monoclonal antibodies that may interfere with the ability of tumor cells to grow and spread. Lomustine is a chemotherapy drug and in a class of medications called alkylating agents. It damages the cell's deoxyribonucleic acid (DNA) and may kill cancer cells. Relatlimab and nivolumab may be safe, tolerable, and/or effective compared to standard of care lomustine in treating patients with recurrent glioblastoma.
Recruitment Criteria
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Accepts Healthy Volunteers
Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms |
No |
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Study Type
An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes. An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes. Searching Both is inclusive of interventional and observational studies. |
Interventional |
| Eligible Ages | 18 Years and Over |
| Gender | All |
Inclusion Criteria:
- - Histologically-proven glioblastoma (World Health Organization [WHO] 2021 criteria) - Progressive or recurrent disease per Response Assessment in Neuro-Oncology (RANO) criteria.
- - No IDH mutation (IDH1 R132H negative by immunohistochemistry [IHC] or sequencing) - Patients must be in first recurrence of glioblastoma following radiation therapy and temozolomide.
- - No prior therapies except radiation, surgery, temozolomide, Tumor Treating Fields (TTFields), and/or Gliadel wafers (placed during the first surgery at diagnosis of glioblastoma multiforme [GBM]).
- - No prior use of nivolumab or other anti-PD1 agents.
- - Patients must be neurologically stable off corticosteroids for at least 5 days prior to registration.
- - Age: ≥ 18 years.
- - Karnofsky Performance Status: ≥ 60% (i.e. patient must be able to care for themselves with occasional help from others) - Absolute lymphocyte count (ALC): ≥ 1000/mm^3.
- - Absolute neutrophil count (ANC): ≥ 1500/mm^3.
- - Platelet count: ≥ 100,000/mm^3.
- - Hemoglobin: ≥ 9.0 g/dL.
- - Activated partial thromboplastin time (APTT) or partial thromboplastin time (PTT): ≤ 1.5 x upper limit of normal (ULN) - Total bilirubin: < 2.0 x ULN (Except for patients with Gilbert's syndrome, who must have direct bilirubin < 2.0 x ULN) - Aspartate aminotransferase (AST) / alanine aminotransferase (ALT): < 3.0 x ULN.
- - Calculated (calc.
- - Thyroid-stimulating hormone (TSH): within normal limits (WNL) (Supplementation is acceptable to achieve a TSH WNL.
- - Not pregnant and not nursing, because this study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown and an agent that has known genotoxic, mutagenic and teratogenic effects.
- - Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.
- - No active brain metastases or leptomeningeal disease.
- - HIV: HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months prior to registration are eligible for this trial.
- - Hepatitis B: For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.
- - Hepatitis C: Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured.
- - No known medical condition causing an inability to swallow oral formulations of agents.
- - No current symptomatic pulmonary disease.
Trial Details
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Trial ID:
This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries. |
NCT06325683 |
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Phase
Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans. Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data. Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs. Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use. |
Phase 2 |
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Lead Sponsor
The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data. |
National Cancer Institute (NCI) |
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Principal Investigator
The person who is responsible for the scientific and technical direction of the entire clinical study. |
Michael Lim |
| Principal Investigator Affiliation | Alliance for Clinical Trials in Oncology |
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Agency Class
Category of organization(s) involved as sponsor (and collaborator) supporting the trial. |
NIH |
| Overall Status | Suspended |
| Countries | United States |
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Conditions
The disease, disorder, syndrome, illness, or injury that is being studied. |
Recurrent Glioblastoma |
PRIMARY OBJECTIVE:
- I. To compare the restricted mean survival time (RMST) for overall survival (OS) between patients receiving the combination of relatlimab (BMS-986016) and nivolumab versus patients receiving standard of care chloroethylcyclohexylnitrosourea (CCNU) (lomustine).
- I. To compare the 12-month OS rates between patients receiving the combination of relatlimab (BMS-986016) and nivolumab versus patients receiving standard of care CCNU (lomustine).
- II. To compare the restricted mean survival times for progression-free survival (PFS) between patients receiving the combination of relatlimab (BMS-986016) and nivolumab versus patients receiving standard of care CCNU (lomustine).
- III. To compare the radiographic response rate between patients receiving the combination of relatlimab (BMS-986016) and nivolumab versus patients receiving standard of care CCNU (lomustine).
- IV. To compare the safety/adverse event rate between patients receiving the combination of relatlimab (BMS-986016) and nivolumab versus patients receiving standard of care CCNU (lomustine).
Arms
Experimental: Arm I (nivolumab, relatlimab)
Patients receive nivolumab IV over 30 minutes followed by relatlimab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo surgery or biopsy, MRI, and blood sample collection throughout study.
Active Comparator: Arm II (lomustine)
Patients receive lomustine PO on day 1 of each cycle. Cycles repeat every 42 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo surgery or biopsy, MRI, and blood sample collection throughout study.
Interventions
Procedure: - Biopsy
Undergo biopsy
Procedure: - Biospecimen Collection
Undergo blood sample collection
Drug: - Lomustine
Given PO
Procedure: - Magnetic Resonance Imaging
Undergo MRI
Biological: - Nivolumab
Given IV
Biological: - Relatlimab
Given IV
Procedure: - Surgical Procedure
Undergo surgery
Contact a Trial Team
If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.
Status
Address
Sutter Auburn Faith Hospital
Auburn, California, 95602
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Kaiser Permanente Los Angeles Medical Center
Los Angeles, California, 90027
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Cedars Sinai Medical Center
Los Angeles, California, 90048
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Kaiser Permanente-San Diego Zion
San Diego, California, 92120
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Yale University
New Haven, Connecticut, 06520
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Address
Smilow Cancer Hospital Care Center-Trumbull
Trumbull, Connecticut, 06611
Status
Address
Beebe South Coastal Health Campus
Millville, Delaware, 19967
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Address
Helen F Graham Cancer Center
Newark, Delaware, 19713
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Address
Medical Oncology Hematology Consultants PA
Newark, Delaware, 19713
Status
Address
Beebe Health Campus
Rehoboth Beach, Delaware, 19971
Status
Address
Saint Alphonsus Cancer Care Center-Boise
Boise, Idaho, 83706
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Address
Saint Luke's Cancer Institute - Boise
Boise, Idaho, 83712
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Address
Saint Alphonsus Cancer Care Center-Caldwell
Caldwell, Idaho, 83605
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Address
Kootenai Health - Coeur d'Alene
Coeur d'Alene, Idaho, 83814
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Saint Luke's Cancer Institute - Fruitland
Fruitland, Idaho, 83619
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Saint Luke's Cancer Institute - Meridian
Meridian, Idaho, 83642
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Saint Alphonsus Cancer Care Center-Nampa
Nampa, Idaho, 83687
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Saint Luke's Cancer Institute - Nampa
Nampa, Idaho, 83687
Status
Address
Kootenai Clinic Cancer Services - Post Falls
Post Falls, Idaho, 83854
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Address
Kootenai Clinic Cancer Services - Sandpoint
Sandpoint, Idaho, 83864
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Address
Illinois CancerCare-Bloomington
Bloomington, Illinois, 61704
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Address
Illinois CancerCare-Canton
Canton, Illinois, 61520
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Address
Illinois CancerCare-Carthage
Carthage, Illinois, 62321
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Address
University of Illinois
Chicago, Illinois, 60612
Status
Address
Cancer Care Specialists of Illinois - Decatur
Decatur, Illinois, 62526
Status
Address
Decatur Memorial Hospital
Decatur, Illinois, 62526
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Address
Illinois CancerCare-Dixon
Dixon, Illinois, 61021
Status
Address
Crossroads Cancer Center
Effingham, Illinois, 62401
Status
Address
Illinois CancerCare-Eureka
Eureka, Illinois, 61530
Status
Address
NorthShore University HealthSystem-Evanston Hospital
Evanston, Illinois, 60201
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Address
Illinois CancerCare-Galesburg
Galesburg, Illinois, 61401
Status
Address
NorthShore University HealthSystem-Glenbrook Hospital
Glenview, Illinois, 60026
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Address
Illinois CancerCare-Kewanee Clinic
Kewanee, Illinois, 61443
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Address
Illinois CancerCare-Macomb
Macomb, Illinois, 61455
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Address
Illinois CancerCare-Ottawa Clinic
Ottawa, Illinois, 61350
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Address
Illinois CancerCare-Pekin
Pekin, Illinois, 61554
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Address
Illinois CancerCare-Peoria
Peoria, Illinois, 61615
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Address
Illinois CancerCare-Peru
Peru, Illinois, 61354
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Address
Illinois CancerCare-Princeton
Princeton, Illinois, 61356
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Address
Memorial Hospital East
Shiloh, Illinois, 62269
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Address
Southern Illinois University School of Medicine
Springfield, Illinois, 62702
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Address
Springfield Clinic
Springfield, Illinois, 62702
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Address
Springfield Memorial Hospital
Springfield, Illinois, 62781
Status
Address
Illinois CancerCare - Washington
Washington, Illinois, 61571
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Address
Franciscan Health Indianapolis
Indianapolis, Indiana, 46237
Status
Address
Mary Greeley Medical Center
Ames, Iowa, 50010
Status
Address
McFarland Clinic - Ames
Ames, Iowa, 50010
Status
Address
Mission Cancer and Blood - Ankeny
Ankeny, Iowa, 50023
Status
Address
McFarland Clinic - Boone
Boone, Iowa, 50036
Status
Address
Saint Anthony Regional Hospital
Carroll, Iowa, 51401
Status
Address
Mercy Hospital
Cedar Rapids, Iowa, 52403
Status
Address
Oncology Associates at Mercy Medical Center
Cedar Rapids, Iowa, 52403
Status
Address
Mission Cancer and Blood - West Des Moines
Clive, Iowa, 50325
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Address
Iowa Methodist Medical Center
Des Moines, Iowa, 50309
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Address
Mission Cancer and Blood - Des Moines
Des Moines, Iowa, 50309
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Address
Broadlawns Medical Center
Des Moines, Iowa, 50314
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Address
Mission Cancer and Blood - Laurel
Des Moines, Iowa, 50314
Status
Address
McFarland Clinic - Trinity Cancer Center
Fort Dodge, Iowa, 50501
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Address
Trinity Regional Medical Center
Fort Dodge, Iowa, 50501
Status
Address
University of Iowa/Holden Comprehensive Cancer Center
Iowa City, Iowa, 52242
Status
Address
McFarland Clinic - Jefferson
Jefferson, Iowa, 50129
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Address
McFarland Clinic - Marshalltown
Marshalltown, Iowa, 50158
Status
Address
University of Kentucky/Markey Cancer Center
Lexington, Kentucky, 40536
Status
Address
Maine Medical Partners - South Portland
South Portland, Maine, 04106
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Address
Tufts Medical Center
Boston, Massachusetts, 02111
Status
Address
Trinity Health Saint Joseph Mercy Hospital Ann Arbor
Ann Arbor, Michigan, 48106
Status
Address
Trinity Health IHA Medical Group Hematology Oncology - Brighton
Brighton, Michigan, 48114
Status
Address
Trinity Health IHA Medical Group Hematology Oncology - Canton
Canton, Michigan, 48188
Status
Address
Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital
Chelsea, Michigan, 48118
Status
Address
Cancer Hematology Centers - Flint
Flint, Michigan, 48503
Status
Address
Genesee Hematology Oncology PC
Flint, Michigan, 48503
Status
Address
Genesys Hurley Cancer Institute
Flint, Michigan, 48503
Status
Address
Hurley Medical Center
Flint, Michigan, 48503
Status
Address
University of Michigan Health - Sparrow Lansing
Lansing, Michigan, 48912
Status
Address
Trinity Health Saint Mary Mercy Livonia Hospital
Livonia, Michigan, 48154
Status
Address
Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus
Ypsilanti, Michigan, 48197
Status
Address
Essentia Health Saint Joseph's Medical Center
Brainerd, Minnesota, 56401
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Address
Essentia Health - Deer River Clinic
Deer River, Minnesota, 56636
Status
Address
Essentia Health Cancer Center
Duluth, Minnesota, 55805
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Address
Essentia Health Hibbing Clinic
Hibbing, Minnesota, 55746
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Address
Essentia Health Sandstone
Sandstone, Minnesota, 55072
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Address
Essentia Health Virginia Clinic
Virginia, Minnesota, 55792
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Address
Saint Francis Medical Center
Cape Girardeau, Missouri, 63703
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Address
Siteman Cancer Center at West County Hospital
Creve Coeur, Missouri, 63141
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Address
Washington University School of Medicine
Saint Louis, Missouri, 63110
Status
Address
Siteman Cancer Center-South County
Saint Louis, Missouri, 63129
Status
Address
Siteman Cancer Center at Christian Hospital
Saint Louis, Missouri, 63136
Status
Address
Siteman Cancer Center at Saint Peters Hospital
Saint Peters, Missouri, 63376
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Address
Billings Clinic Cancer Center
Billings, Montana, 59101
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Address
Bozeman Health Deaconess Hospital
Bozeman, Montana, 59715
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Address
Benefis Sletten Cancer Institute
Great Falls, Montana, 59405
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Address
Community Medical Center
Missoula, Montana, 59804
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Address
Hackensack University Medical Center
Hackensack, New Jersey, 07601
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Address
Morristown Medical Center
Morristown, New Jersey, 07960
Status
Address
Overlook Hospital
Summit, New Jersey, 07902
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Address
Montefiore Medical Center-Einstein Campus
Bronx, New York, 10461
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Address
Glens Falls Hospital
Glens Falls, New York, 12801
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Address
NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
New York, New York, 10032
Status
Address
FirstHealth of the Carolinas-Moore Regional Hospital
Pinehurst, North Carolina, 28374
Status
Address
Essentia Health Cancer Center-South University Clinic
Fargo, North Dakota, 58103
Status
Address
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210
Status
Address
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, 73104
Status
Address
Saint Alphonsus Cancer Care Center-Ontario
Ontario, Oregon, 97914
Status
Address
Providence Portland Medical Center
Portland, Oregon, 97213
Status
Address
Providence Saint Vincent Medical Center
Portland, Oregon, 97225
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Address
Lehigh Valley Hospital-Cedar Crest
Allentown, Pennsylvania, 18103
Status
Address
Lehigh Valley Hospital - Muhlenberg
Bethlehem, Pennsylvania, 18017
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Address
Pocono Medical Center
East Stroudsburg, Pennsylvania, 18301
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Address
Thomas Jefferson University Hospital
Philadelphia, Pennsylvania, 19107
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Address
Allegheny General Hospital
Pittsburgh, Pennsylvania, 15212
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Address
Wexford Health and Wellness Pavilion
Wexford, Pennsylvania, 15090
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Address
University of Vermont Medical Center
Burlington, Vermont, 05401
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Address
University of Vermont and State Agricultural College
Burlington, Vermont, 05405
Status
Address
Inova Schar Cancer Institute
Fairfax, Virginia, 22031
Status
Address
Duluth Clinic Ashland
Ashland, Wisconsin, 54806
Status
Address
University of Wisconsin Carbone Cancer Center - Eastpark Medical Center
Madison, Wisconsin, 53718
Status
Address
University of Wisconsin Carbone Cancer Center - University Hospital
Madison, Wisconsin, 53792
