Brentuximab Vedotin and Nivolumab With or Without Ipilimumab in Treating Patients With Relapsed or Refractory Hodgkin Lymphoma

April 13, 2024 updated by: National Cancer Institute (NCI)

A Phase I Study With an Expansion Cohort/Randomized Phase II Study of the Combinations of Ipilimumab, Nivolumab and Brentuximab Vedotin in Patients With Relapsed/Refractory Hodgkin Lymphoma

This phase I/II trial studies the side effects and best dose of ipilimumab and nivolumab when given together with brentuximab vedotin, and how well they work in treating patients with Hodgkin lymphoma that has returned after a period of improvement (recurrent) or has not responded to previous treatment (refractory). Immunotherapy with monoclonal antibodies, such as ipilimumab and nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of cancer cells to grow and spread. Brentuximab vedotin is a monoclonal antibody, brentuximab, linked to a toxic agent called vedotin. Brentuximab attaches to CD30 positive cancer cells in a targeted way and delivers vedotin to kill them. It is not known whether giving brentuximab vedotin and nivolumab with or without ipilimumab may kill more cancer cells.

Study Overview

Status

Suspended

Conditions

Intervention / Treatment

Detailed Description

PRIMARY OBJECTIVES:

I. To determine the maximum tolerated dose (MTD) and dose limiting toxicities (DLT) of the combinations of brentuximab vedotin and ipilimumab, brentuximab vedotin and nivolumab, and brentuximab vedotin, ipilimumab, and nivolumab. (Phase I) II. To evaluate the complete response (CR) rate for the regimens of brentuximab vedotin and nivolumab compared to brentuximab vedotin, ipilimumab, and nivolumab. (Phase II; adult cohort [aged >= 18 years]) III. To characterize the safety and toxicity of treatment combination in the pediatric population. (Phase II; pediatric cohort [aged 12-17 years])

SECONDARY OBJECTIVES:

I. To evaluate complete response (CR) rate, partial response (PR) rate and overall response rate (ORR), for the combinations of brentuximab vedotin and ipilimumab, brentuximab vedotin and nivolumab, and brentuximab vedotin, ipilimumab, and nivolumab. (Phase I) II. To evaluate the duration of remission (DOR) to these combinations and compare with the DOR achieved with the most recent prior systemic therapy. (Phase I) III. To evaluate the progression-free survival (PFS) and the overall survival (OS) in patients receiving the combination of brentuximab vedotin and ipilimumab, brentuximab vedotin and nivolumab, and brentuximab vedotin, ipilimumab, and nivolumab. (Phase I) IV. To evaluate the ORR, PR, and stable disease (SD) rate for the combinations of brentuximab vedotin and nivolumab and brentuximab vedotin, ipilimumab, and nivolumab. (Phase II) V. To evaluate the DOR to these combinations and compare with the DOR achieved with the most recent prior systemic therapy. (Phase II) VI. To evaluate the 5 year PFS and OS in patients receiving the combinations of brentuximab vedotin and nivolumab and brentuximab vedotin, ipilimumab, and nivolumab. (Phase II) VII. To further evaluate the safety and characterize the toxicity for the combinations of brentuximab vedotin and nivolumab, and brentuximab vedotin, ipilimumab, and nivolumab. (Phase II)

CORRELATIVE STUDY OBJECTIVES:

I. To evaluate the ability of these combinations to alter tumor specific T cell immunity. (Phase I) II. To evaluate the effects of these combinations on systemic immunity. (Phase I) III. To evaluate a panel of cytokine and T cell specific biomarkers from the peripheral blood as a potential immune signature of treatment response to therapy with these combinations for patients with relapsed/refractory Hodgkin lymphoma (HL). (Phase I) IV. To evaluate using gene expression profiling (GEP) a signature of response to these novel combinations of an antibody drug conjugate with immunomodulatory therapy. (Phase I) V. To evaluate the ability of these combinations to alter tumor specific T cell immunity, and circulating T cell phenotypes, in patients as a function of treatment response at multiple timepoints during therapy. (Phase II) VI. To evaluate peripheral blood cytokine profiles in responding and resistant patients at multiple timepoints during therapy. (Phase II) VII. To evaluate using GEP a signature of response versus (vs.) resistance to these novel combinations of an antibody drug conjugate with immunomodulatory therapy. (Phase II) VIII. To evaluate the influence of human gut microbiome dysbiosis on HL lymphomagenesis and the systemic immune response. (Phase II)

IMAGING CORRELATIVE STUDY OBJECTIVES:

I. To evaluate atypical response patterns with currently available response evaluation criteria. (Phase II) II. To correlate response evaluated using currently available response evaluation criteria with duration of response (PFS, event free survival [EFS], failure free survival [FFS]). (Phase II) III. To evaluate response patterns in different immunotherapy treatment schemes and correlate with historical data using chemotherapy. (Phase II) IV. To correlate imaging changes in all treatment schemes quantitatively with PFS. (Phase II)

EXPLORATORY OBJECTIVES:

I. Evaluate outcomes (CR, PFS) between patients with/without prior transplants. (Phase II) II. Evaluate outcomes (PFS, OS) between the patients who stay on treatment and do not go to transplant in both arms (the post auto and the few others who don't want transplant) vs the patients who go off for transplant. (Phase II) III. Evaluate outcomes (CR, PFS) in pediatric population (age 12 to < 18 years of age) vs. adult population. (Phase II)

OUTLINE: This is a phase I, dose-escalation study of brentuximab vedotin, ipilimumab, and nivolumab followed by a phase II study.

PHASE I: Patients are assigned into 1 of 3 arms.

ARM I: Patients receive brentuximab vedotin intravenously (IV) over 90 minutes on day 1 of cycles 1-16 and ipilimumab IV over 30 minutes on day 1 of cycles 1-4, 8, 12, and 16. Treatment repeats every 21 days for up to 16 cycles in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive brentuximab vedotin IV over 90 minutes on day 1 of cycles 1-16 and nivolumab IV over 30 minutes on day 1 of cycles 1-46. Treatment repeats every 21 days for up to 16 cycles and every 14 days beginning cycle 17 for up to 46 cycles in the absence of disease progression or unacceptable toxicity.

ARM III: Patients receive brentuximab vedotin IV over 90 minutes on day 1 of cycles 1-16, nivolumab IV over 30 minutes on day 1 of cycles 1-46, and ipilimumab IV over 30 minutes on day 1 every 12 weeks for up to 9 doses. Treatment repeats every 21 days for up to 16 cycles and every 14 days beginning cycle 17 for up to 46 cycles in the absence of disease progression or unacceptable toxicity.

PHASE II: Patients are randomized to 1 of 2 arms.

ARM I: Patients receive brentuximab vedotin IV over 30 minutes on day 1 of cycles 1-16 and nivolumab IV over 90 minutes on day 1 of cycles 1-34. Treatment repeats every 21 days for up to 34 cycles in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive brentuximab vedotin IV over 90 minutes on day 1 of cycles 1-16, nivolumab IV over 30 minutes on day 1 of cycles 1-34, and ipilimumab IV over 30 minutes on day 1 every 12 weeks for up to 9 doses. Treatment repeats every 21 days for up to 34 cycles in the absence of disease progression or unacceptable toxicity.

All patients also undergo computed tomography (CT) or positron emission tomography (PET) scan throughout the trial. Patients undergo blood sample collection and may undergo tumor biopsy on study.

After completion of phase I study treatment, patients are followed up every 3 months for 1 year, then every 6 months for 2 years. After completion of phase II study treatment, patients are followed up for 10 years.

Study Type

Interventional

Enrollment (Estimated)

146

Phase

Phase 2
Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

United States
- Alabama
  - Birmingham, Alabama, United States, 35233
    - University of Alabama at Birmingham Cancer Center
  - Birmingham, Alabama, United States, 35233
    - Children's Hospital of Alabama
- Alaska
  - Anchorage, Alaska, United States, 98508
    - Anchorage Associates in Radiation Medicine
  - Anchorage, Alaska, United States, 99508
    - Alaska Breast Care and Surgery LLC
  - Anchorage, Alaska, United States, 99508
    - Alaska Oncology and Hematology LLC
  - Anchorage, Alaska, United States, 99508
    - Alaska Women's Cancer Care
  - Anchorage, Alaska, United States, 99508
    - Anchorage Oncology Centre
  - Anchorage, Alaska, United States, 99508
    - Katmai Oncology Group
  - Anchorage, Alaska, United States, 99508
    - Providence Alaska Medical Center
  - Anchorage, Alaska, United States, 99504
    - Anchorage Radiation Therapy Center
  - Fairbanks, Alaska, United States, 99701
    - Fairbanks Memorial Hospital
- Arizona
  - Kingman, Arizona, United States, 86401
    - Kingman Regional Medical Center
  - Phoenix, Arizona, United States, 85004
    - Cancer Center at Saint Joseph's
- Arkansas
  - Fort Smith, Arkansas, United States, 72903
    - Mercy Hospital Fort Smith
  - Hot Springs, Arkansas, United States, 71913
    - CHI Saint Vincent Cancer Center Hot Springs
- California
  - Antioch, California, United States, 94531
    - Kaiser Permanente-Deer Valley Medical Center
  - Arroyo Grande, California, United States, 93420
    - PCR Oncology
  - Arroyo Grande, California, United States, 93420
    - Mission Hope Medical Oncology - Arroyo Grande
  - Burbank, California, United States, 91505
    - Providence Saint Joseph Medical Center/Disney Family Cancer Center
  - Dublin, California, United States, 94568
    - Kaiser Permanente Dublin
  - Fremont, California, United States, 94538
    - Kaiser Permanente-Fremont
  - Fresno, California, United States, 93720
    - Kaiser Permanente-Fresno
  - Fresno, California, United States, 93720
    - Fresno Cancer Center
  - Modesto, California, United States, 95356
    - Kaiser Permanente-Modesto
  - Oakland, California, United States, 94611
    - Kaiser Permanente-Oakland
  - Oakland, California, United States, 94611
    - Kaiser Permanente Oakland-Broadway
  - Orange, California, United States, 92868
    - Children's Hospital of Orange County
  - Palo Alto, California, United States, 94304
    - Stanford Cancer Institute Palo Alto
  - Rancho Cordova, California, United States, 95670
    - Kaiser Permanente-Rancho Cordova Cancer Center
  - Redwood City, California, United States, 94063
    - Kaiser Permanente-Redwood City
  - Richmond, California, United States, 94801
    - Kaiser Permanente-Richmond
  - Rohnert Park, California, United States, 94928
    - Rohnert Park Cancer Center
  - Roseville, California, United States, 95678
    - The Permanente Medical Group-Roseville Radiation Oncology
  - Roseville, California, United States, 95661
    - Kaiser Permanente-Roseville
  - Sacramento, California, United States, 95814
    - Kaiser Permanente Downtown Commons
  - Sacramento, California, United States, 95823
    - Kaiser Permanente-South Sacramento
  - Sacramento, California, United States, 95823
    - South Sacramento Cancer Center
  - Sacramento, California, United States, 95825
    - Kaiser Permanente - Sacramento
  - San Francisco, California, United States, 94115
    - Kaiser Permanente-San Francisco
  - San Francisco, California, United States, 94158
    - UCSF Medical Center-Mission Bay
  - San Jose, California, United States, 95119
    - Kaiser Permanente-Santa Teresa-San Jose
  - San Leandro, California, United States, 94577
    - Kaiser Permanente San Leandro
  - San Luis Obispo, California, United States, 93401
    - Pacific Central Coast Health Center-San Luis Obispo
  - San Rafael, California, United States, 94903
    - Kaiser San Rafael-Gallinas
  - San Rafael, California, United States, 94903
    - Kaiser Permanente-San Rafael
  - Santa Clara, California, United States, 95051
    - Kaiser Permanente Medical Center - Santa Clara
  - Santa Maria, California, United States, 93444
    - Mission Hope Medical Oncology - Santa Maria
  - Santa Rosa, California, United States, 95403
    - Kaiser Permanente-Santa Rosa
  - South San Francisco, California, United States, 94080
    - Kaiser Permanente Cancer Treatment Center
  - South San Francisco, California, United States, 94080
    - Kaiser Permanente-South San Francisco
  - Stockton, California, United States, 95210
    - Kaiser Permanente-Stockton
  - Vacaville, California, United States, 95688
    - Kaiser Permanente Medical Center-Vacaville
  - Vallejo, California, United States, 94589
    - Kaiser Permanente-Vallejo
  - Walnut Creek, California, United States, 94596
    - Kaiser Permanente-Walnut Creek
- Colorado
  - Aurora, Colorado, United States, 80012
    - Rocky Mountain Cancer Centers-Aurora
  - Aurora, Colorado, United States, 80012
    - The Medical Center of Aurora
  - Boulder, Colorado, United States, 80301
    - Boulder Community Hospital
  - Boulder, Colorado, United States, 80303
    - Boulder Community Foothills Hospital
  - Boulder, Colorado, United States, 80304
    - Rocky Mountain Cancer Centers-Boulder
  - Centennial, Colorado, United States, 80112
    - Rocky Mountain Cancer Centers - Centennial
  - Colorado Springs, Colorado, United States, 80907
    - Penrose-Saint Francis Healthcare
  - Colorado Springs, Colorado, United States, 80907
    - Rocky Mountain Cancer Centers-Penrose
  - Denver, Colorado, United States, 80210
    - Porter Adventist Hospital
  - Denver, Colorado, United States, 80218
    - Presbyterian - Saint Lukes Medical Center - Health One
  - Denver, Colorado, United States, 80218
    - Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center
  - Denver, Colorado, United States, 80218
    - SCL Health Saint Joseph Hospital
  - Denver, Colorado, United States, 80220
    - Rose Medical Center
  - Denver, Colorado, United States, 80218
    - Rocky Mountain Cancer Centers-Midtown
  - Denver, Colorado, United States, 80220
    - Rocky Mountain Cancer Centers-Rose
  - Denver, Colorado, United States, 80204
    - Denver Health Medical Center
  - Denver, Colorado, United States, 80218
    - Colorado Blood Cancer Institute
  - Denver, Colorado, United States, 80204
    - Cancer Center of Colorado at Sloan's Lake
  - Denver, Colorado, United States, 80209
    - The Women's Imaging Center
  - Denver, Colorado, United States, 80206
    - National Jewish Health-Main Campus
  - Denver, Colorado, United States, 80220
    - Western Surgical Care
  - Durango, Colorado, United States, 81301
    - Mercy Medical Center
  - Durango, Colorado, United States, 81301
    - Southwest Oncology PC
  - Englewood, Colorado, United States, 80113
    - Mountain Blue Cancer Care Center - Swedish
  - Englewood, Colorado, United States, 80113
    - Swedish Medical Center
  - Englewood, Colorado, United States, 80113
    - Rocky Mountain Cancer Centers - Swedish
  - Golden, Colorado, United States, 80401
    - Mountain Blue Cancer Care Center
  - Golden, Colorado, United States, 80401
    - National Jewish Health-Western Hematology Oncology
  - Grand Junction, Colorado, United States, 81501
    - Saint Mary's Hospital and Regional Medical Center
  - Greeley, Colorado, United States, 80631
    - North Colorado Medical Center
  - Lafayette, Colorado, United States, 80026
    - Good Samaritan Medical Center
  - Lakewood, Colorado, United States, 80228
    - Saint Anthony Hospital
  - Lakewood, Colorado, United States, 80228
    - Rocky Mountain Cancer Centers-Lakewood
  - Littleton, Colorado, United States, 80120
    - Rocky Mountain Cancer Centers-Littleton
  - Littleton, Colorado, United States, 80122
    - Littleton Adventist Hospital
  - Lone Tree, Colorado, United States, 80124
    - Sky Ridge Medical Center
  - Lone Tree, Colorado, United States, 80124
    - Rocky Mountain Cancer Centers-Sky Ridge
  - Longmont, Colorado, United States, 80501
    - Longmont United Hospital
  - Longmont, Colorado, United States, 80501
    - Rocky Mountain Cancer Centers-Longmont
  - Loveland, Colorado, United States, 80539
    - McKee Medical Center
  - Parker, Colorado, United States, 80138
    - Parker Adventist Hospital
  - Parker, Colorado, United States, 80138
    - Rocky Mountain Cancer Centers-Parker
  - Pueblo, Colorado, United States, 81008
    - Rocky Mountain Cancer Centers - Pueblo
  - Thornton, Colorado, United States, 80260
    - Rocky Mountain Cancer Centers-Thornton
  - Thornton, Colorado, United States, 80260
    - National Jewish Health-Northern Hematology Oncology
  - Wheat Ridge, Colorado, United States, 80033
    - SCL Health Lutheran Medical Center
- District of Columbia
  - Washington, District of Columbia, United States, 20010
    - Children's National Medical Center
- Florida
  - Fort Myers, Florida, United States, 33905
    - Regional Cancer Center-Lee Memorial Health System
  - Fort Myers, Florida, United States, 33908
    - Golisano Children's Hospital of Southwest Florida
  - Saint Petersburg, Florida, United States, 33701
    - Johns Hopkins All Children's Hospital
  - Tampa, Florida, United States, 33606
    - Tampa General Hospital
  - Tampa, Florida, United States, 33607
    - Saint Joseph's Hospital/Children's Hospital-Tampa
- Georgia
  - Atlanta, Georgia, United States, 30322
    - Emory University Hospital/Winship Cancer Institute
  - Atlanta, Georgia, United States, 30322
    - Children's Healthcare of Atlanta - Egleston
- Hawaii
  - Honolulu, Hawaii, United States, 96819
    - Kaiser Permanente Moanalua Medical Center
- Idaho
  - Boise, Idaho, United States, 83706
    - Saint Alphonsus Cancer Care Center-Boise
  - Boise, Idaho, United States, 83712
    - Saint Luke's Cancer Institute - Boise
  - Caldwell, Idaho, United States, 83605
    - Saint Alphonsus Cancer Care Center-Caldwell
  - Coeur d'Alene, Idaho, United States, 83814
    - Kootenai Health - Coeur d'Alene
  - Emmett, Idaho, United States, 83617
    - Walter Knox Memorial Hospital
  - Fruitland, Idaho, United States, 83619
    - Saint Luke's Cancer Institute - Fruitland
  - Meridian, Idaho, United States, 83642
    - Idaho Urologic Institute-Meridian
  - Meridian, Idaho, United States, 83642
    - Saint Luke's Cancer Institute - Meridian
  - Nampa, Idaho, United States, 83686
    - Saint Luke's Cancer Institute - Nampa
  - Nampa, Idaho, United States, 83687
    - Saint Alphonsus Cancer Care Center-Nampa
  - Post Falls, Idaho, United States, 83854
    - Kootenai Clinic Cancer Services - Post Falls
  - Sandpoint, Idaho, United States, 83864
    - Kootenai Cancer Clinic
  - Twin Falls, Idaho, United States, 83301
    - Saint Luke's Cancer Institute - Twin Falls
- Illinois
  - Alton, Illinois, United States, 62002
    - Saint Anthony's Health
  - Aurora, Illinois, United States, 60504
    - Rush - Copley Medical Center
  - Bloomington, Illinois, United States, 61704
    - Illinois CancerCare-Bloomington
  - Canton, Illinois, United States, 61520
    - Illinois CancerCare-Canton
  - Carbondale, Illinois, United States, 62902
    - Memorial Hospital of Carbondale
  - Carterville, Illinois, United States, 62918
    - SIH Cancer Institute
  - Carthage, Illinois, United States, 62321
    - Illinois CancerCare-Carthage
  - Centralia, Illinois, United States, 62801
    - Centralia Oncology Clinic
  - Chicago, Illinois, United States, 60611
    - Northwestern University
  - Chicago, Illinois, United States, 60612
    - Rush University Medical Center
  - Chicago, Illinois, United States, 60612
    - University of Illinois
  - Danville, Illinois, United States, 61832
    - Carle at The Riverfront
  - Decatur, Illinois, United States, 62526
    - Decatur Memorial Hospital
  - Decatur, Illinois, United States, 62526
    - Cancer Care Specialists of Illinois - Decatur
  - Dixon, Illinois, United States, 61021
    - Illinois CancerCare-Dixon
  - Effingham, Illinois, United States, 62401
    - Crossroads Cancer Center
  - Effingham, Illinois, United States, 62401
    - Carle Physician Group-Effingham
  - Eureka, Illinois, United States, 61530
    - Illinois CancerCare-Eureka
  - Galesburg, Illinois, United States, 61401
    - Western Illinois Cancer Treatment Center
  - Galesburg, Illinois, United States, 61401
    - Illinois CancerCare-Galesburg
  - Joliet, Illinois, United States, 60435
    - Duly Health and Care Joliet
  - Kewanee, Illinois, United States, 61443
    - Illinois CancerCare-Kewanee Clinic
  - Macomb, Illinois, United States, 61455
    - Illinois CancerCare-Macomb
  - Mattoon, Illinois, United States, 61938
    - Carle Physician Group-Mattoon/Charleston
  - Mount Vernon, Illinois, United States, 62864
    - Good Samaritan Regional Health Center
  - O'Fallon, Illinois, United States, 62269
    - Cancer Care Center of O'Fallon
  - Ottawa, Illinois, United States, 61350
    - Illinois CancerCare-Ottawa Clinic
  - Pekin, Illinois, United States, 61554
    - Illinois CancerCare-Pekin
  - Peoria, Illinois, United States, 61636
    - Methodist Medical Center of Illinois
  - Peoria, Illinois, United States, 61615
    - Illinois CancerCare-Peoria
  - Peru, Illinois, United States, 61354
    - Illinois CancerCare-Peru
  - Peru, Illinois, United States, 61354
    - Valley Radiation Oncology
  - Princeton, Illinois, United States, 61356
    - Illinois CancerCare-Princeton
  - Springfield, Illinois, United States, 62781
    - Memorial Medical Center
  - Springfield, Illinois, United States, 62702
    - Southern Illinois University School of Medicine
  - Springfield, Illinois, United States, 62702
    - Springfield Clinic
  - Swansea, Illinois, United States, 62226
    - Southwest Illinois Health Services LLP
  - Urbana, Illinois, United States, 61801
    - Carle Cancer Center
  - Urbana, Illinois, United States, 61801
    - The Carle Foundation Hospital
  - Washington, Illinois, United States, 61571
    - Illinois CancerCare - Washington
  - Yorkville, Illinois, United States, 60560
    - Rush-Copley Healthcare Center
- Indiana
  - Evansville, Indiana, United States, 47713
    - Deaconess Clinic Downtown
  - Indianapolis, Indiana, United States, 46202
    - Indiana University/Melvin and Bren Simon Cancer Center
  - Newburgh, Indiana, United States, 47630
    - Chancellor Center for Oncology
- Iowa
  - Clive, Iowa, United States, 50325
    - Mercy Cancer Center-West Lakes
  - Clive, Iowa, United States, 50325
    - Medical Oncology and Hematology Associates-West Des Moines
  - Council Bluffs, Iowa, United States, 51503
    - Alegent Health Mercy Hospital
  - Creston, Iowa, United States, 50801
    - Greater Regional Medical Center
  - Des Moines, Iowa, United States, 50314
    - Mercy Medical Center - Des Moines
  - Des Moines, Iowa, United States, 50314
    - Mission Cancer and Blood - Laurel
  - West Des Moines, Iowa, United States, 50266
    - Mercy Medical Center-West Lakes
- Kansas
  - Garden City, Kansas, United States, 67846
    - Central Care Cancer Center - Garden City
  - Great Bend, Kansas, United States, 67530
    - Central Care Cancer Center - Great Bend
- Kentucky
  - Bardstown, Kentucky, United States, 40004
    - Flaget Memorial Hospital
  - Corbin, Kentucky, United States, 40701
    - Commonwealth Cancer Center-Corbin
  - Lexington, Kentucky, United States, 40504
    - Saint Joseph Radiation Oncology Resource Center
  - Lexington, Kentucky, United States, 40509
    - Saint Joseph Hospital East
  - London, Kentucky, United States, 40741
    - Saint Joseph London
  - Louisville, Kentucky, United States, 40202
    - Jewish Hospital
  - Louisville, Kentucky, United States, 40245
    - UofL Health Medical Center Northeast
  - Louisville, Kentucky, United States, 40215
    - Saints Mary and Elizabeth Hospital
  - Paducah, Kentucky, United States, 42003
    - Mercy Health - Paducah Medical Oncology and Hematology
  - Shepherdsville, Kentucky, United States, 40165
    - Jewish Hospital Medical Center South
- Louisiana
  - Baton Rouge, Louisiana, United States, 70805
    - LSU Health Baton Rouge-North Clinic
  - Baton Rouge, Louisiana, United States, 70809
    - Louisiana Hematology Oncology Associates LLC
  - Baton Rouge, Louisiana, United States, 70809
    - Mary Bird Perkins Cancer Center
  - Baton Rouge, Louisiana, United States, 70809
    - Our Lady of the Lake Physicians Group - Medical Oncology
  - Baton Rouge, Louisiana, United States, 70808
    - Our Lady of The Lake
  - Covington, Louisiana, United States, 70433
    - Northshore Oncology Associates-Covington
  - Houma, Louisiana, United States, 70360
    - Terrebonne General Medical Center
  - Houma, Louisiana, United States, 70360
    - Oncology Center of The South Incorporated
- Maryland
  - Baltimore, Maryland, United States, 21287
    - Johns Hopkins University/Sidney Kimmel Cancer Center
  - Baltimore, Maryland, United States, 21229
    - Saint Agnes Hospital
  - Bethesda, Maryland, United States, 20889-5600
    - Walter Reed National Military Medical Center
- Massachusetts
  - Boston, Massachusetts, United States, 02111
    - Tufts Medical Center
- Michigan
  - Port Huron, Michigan, United States, 48060
    - Lake Huron Medical Center
  - Port Huron, Michigan, United States, 48060
    - Huron Medical Center PC
- Minnesota
  - Aitkin, Minnesota, United States, 56431
    - Riverwood Healthcare Center
  - Brainerd, Minnesota, United States, 56401
    - Essentia Health Saint Joseph's Medical Center
  - Deer River, Minnesota, United States, 56636
    - Essentia Health - Deer River Clinic
  - Detroit Lakes, Minnesota, United States, 56501
    - Essentia Health Saint Mary's - Detroit Lakes Clinic
  - Duluth, Minnesota, United States, 55805
    - Essentia Health Cancer Center
  - Duluth, Minnesota, United States, 55805
    - Essentia Health Saint Mary's Medical Center
  - Duluth, Minnesota, United States, 55805
    - Miller-Dwan Hospital
  - Fergus Falls, Minnesota, United States, 56537
    - Lake Region Healthcare Corporation-Cancer Care
  - Fosston, Minnesota, United States, 56542
    - Essentia Health - Fosston
  - Hibbing, Minnesota, United States, 55746
    - Essentia Health Hibbing Clinic
  - Park Rapids, Minnesota, United States, 56470
    - Essentia Health - Park Rapids
  - Rochester, Minnesota, United States, 55905
    - Mayo Clinic in Rochester
  - Sandstone, Minnesota, United States, 55072
    - Essentia Health Sandstone
  - Virginia, Minnesota, United States, 55792
    - Essentia Health Virginia Clinic
- Missouri
  - Ballwin, Missouri, United States, 63011
    - Saint Louis Cancer and Breast Institute-Ballwin
  - Bolivar, Missouri, United States, 65613
    - Central Care Cancer Center - Bolivar
  - Bonne Terre, Missouri, United States, 63628
    - Parkland Health Center-Bonne Terre
  - Branson, Missouri, United States, 65616
    - Cox Cancer Center Branson
  - Cape Girardeau, Missouri, United States, 63703
    - Saint Francis Medical Center
  - Cape Girardeau, Missouri, United States, 63703
    - Southeast Cancer Center
  - Chesterfield, Missouri, United States, 63017
    - Saint Luke's Hospital
  - Creve Coeur, Missouri, United States, 63141
    - Siteman Cancer Center at West County Hospital
  - Farmington, Missouri, United States, 63640
    - Parkland Health Center - Farmington
  - Jefferson City, Missouri, United States, 65109
    - Capital Region Southwest Campus
  - Joplin, Missouri, United States, 64804
    - Freeman Health System
  - Joplin, Missouri, United States, 64804
    - Mercy Hospital Joplin
  - Kansas City, Missouri, United States, 64108
    - Children's Mercy Hospitals and Clinics
  - Rolla, Missouri, United States, 65401
    - Delbert Day Cancer Institute at PCRMC
  - Rolla, Missouri, United States, 65401
    - Mercy Clinic-Rolla-Cancer and Hematology
  - Saint Joseph, Missouri, United States, 64506
    - Heartland Regional Medical Center
  - Saint Louis, Missouri, United States, 63110
    - Washington University School of Medicine
  - Saint Louis, Missouri, United States, 63131
    - Missouri Baptist Medical Center
  - Saint Louis, Missouri, United States, 63141
    - Mercy Hospital Saint Louis
  - Saint Louis, Missouri, United States, 63128
    - Mercy Hospital South
  - Saint Louis, Missouri, United States, 63129
    - Siteman Cancer Center-South County
  - Saint Louis, Missouri, United States, 63136
    - Siteman Cancer Center at Christian Hospital
  - Saint Louis, Missouri, United States, 63109
    - Saint Louis Cancer and Breast Institute-South City
  - Saint Peters, Missouri, United States, 63376
    - Siteman Cancer Center at Saint Peters Hospital
  - Sainte Genevieve, Missouri, United States, 63670
    - Sainte Genevieve County Memorial Hospital
  - Springfield, Missouri, United States, 65807
    - CoxHealth South Hospital
  - Springfield, Missouri, United States, 65804
    - Mercy Hospital Springfield
  - Sullivan, Missouri, United States, 63080
    - Missouri Baptist Sullivan Hospital
  - Sunset Hills, Missouri, United States, 63127
    - BJC Outpatient Center at Sunset Hills
  - Washington, Missouri, United States, 63090
    - Mercy Hospital Washington
- Montana
  - Anaconda, Montana, United States, 59711
    - Community Hospital of Anaconda
  - Billings, Montana, United States, 59101
    - Billings Clinic Cancer Center
  - Billings, Montana, United States, 59101
    - Saint Vincent Healthcare
  - Billings, Montana, United States, 59102
    - Saint Vincent Frontier Cancer Center
  - Bozeman, Montana, United States, 59715
    - Bozeman Deaconess Hospital
  - Butte, Montana, United States, 59701
    - Saint James Community Hospital and Cancer Treatment Center
  - Great Falls, Montana, United States, 59405
    - Great Falls Clinic
  - Great Falls, Montana, United States, 59405
    - Benefis Healthcare- Sletten Cancer Institute
  - Helena, Montana, United States, 59601
    - Saint Peter's Community Hospital
  - Kalispell, Montana, United States, 59901
    - Kalispell Regional Medical Center
  - Missoula, Montana, United States, 59804
    - Community Medical Hospital
  - Missoula, Montana, United States, 59802
    - Saint Patrick Hospital - Community Hospital
- Nebraska
  - Grand Island, Nebraska, United States, 68803
    - CHI Health Saint Francis
  - Kearney, Nebraska, United States, 68847
    - CHI Health Good Samaritan
  - Kearney, Nebraska, United States, 68845
    - Heartland Hematology and Oncology
  - Lincoln, Nebraska, United States, 68510
    - Saint Elizabeth Regional Medical Center
  - Omaha, Nebraska, United States, 68124
    - Alegent Health Bergan Mercy Medical Center
  - Omaha, Nebraska, United States, 68122
    - Alegent Health Immanuel Medical Center
  - Omaha, Nebraska, United States, 68130
    - Alegent Health Lakeside Hospital
  - Omaha, Nebraska, United States, 68131
    - Creighton University Medical Center
  - Omaha, Nebraska, United States, 68122
    - Hematology and Oncology Consultants PC
  - Papillion, Nebraska, United States, 68046
    - Midlands Community Hospital
- Nevada
  - Carson City, Nevada, United States, 89703
    - Carson Tahoe Regional Medical Center
  - Henderson, Nevada, United States, 89052
    - Comprehensive Cancer Centers of Nevada - Henderson
  - Henderson, Nevada, United States, 89052
    - OptumCare Cancer Care at Seven Hills
  - Henderson, Nevada, United States, 89052
    - Cancer and Blood Specialists-Henderson
  - Henderson, Nevada, United States, 89052
    - Las Vegas Cancer Center-Henderson
  - Henderson, Nevada, United States, 89074
    - Comprehensive Cancer Centers of Nevada-Southeast Henderson
  - Henderson, Nevada, United States, 89074
    - GenesisCare USA - Henderson
  - Henderson, Nevada, United States, 89052
    - Comprehensive Cancer Centers of Nevada-Horizon Ridge
  - Henderson, Nevada, United States, 89074
    - Las Vegas Urology - Green Valley
  - Henderson, Nevada, United States, 89074
    - Las Vegas Urology - Pebble
  - Henderson, Nevada, United States, 89074
    - Urology Specialists of Nevada - Green Valley
  - Las Vegas, Nevada, United States, 89144
    - Summerlin Hospital Medical Center
  - Las Vegas, Nevada, United States, 89109
    - Sunrise Hospital and Medical Center
  - Las Vegas, Nevada, United States, 89102
    - OptumCare Cancer Care at Charleston
  - Las Vegas, Nevada, United States, 89106
    - Radiation Oncology Centers of Nevada Central
  - Las Vegas, Nevada, United States, 89109
    - GenesisCare USA - Las Vegas
  - Las Vegas, Nevada, United States, 89119
    - Radiation Oncology Centers of Nevada Southeast
  - Las Vegas, Nevada, United States, 89128
    - Comprehensive Cancer Centers of Nevada - Northwest
  - Las Vegas, Nevada, United States, 89128
    - OptumCare Cancer Care at MountainView
  - Las Vegas, Nevada, United States, 89135
    - Alliance for Childhood Diseases/Cure 4 the Kids Foundation
  - Las Vegas, Nevada, United States, 89144
    - Comprehensive Cancer Centers of Nevada - Town Center
  - Las Vegas, Nevada, United States, 89144
    - Comprehensive Cancer Centers of Nevada-Summerlin
  - Las Vegas, Nevada, United States, 89148
    - Comprehensive Cancer Centers of Nevada
  - Las Vegas, Nevada, United States, 89148
    - OptumCare Cancer Care at Fort Apache
  - Las Vegas, Nevada, United States, 89169
    - Comprehensive Cancer Centers of Nevada - Central Valley
  - Las Vegas, Nevada, United States, 89102
    - University Medical Center of Southern Nevada
  - Las Vegas, Nevada, United States, 89106
    - Cancer and Blood Specialists-Shadow
  - Las Vegas, Nevada, United States, 89109
    - HealthCare Partners Medical Group Oncology/Hematology-Maryland Parkway
  - Las Vegas, Nevada, United States, 89113
    - HealthCare Partners Medical Group Oncology/Hematology-San Martin
  - Las Vegas, Nevada, United States, 89128
    - Cancer and Blood Specialists-Tenaya
  - Las Vegas, Nevada, United States, 89128
    - GenesisCare USA - Vegas Tenaya
  - Las Vegas, Nevada, United States, 89128
    - HealthCare Partners Medical Group Oncology/Hematology-Tenaya
  - Las Vegas, Nevada, United States, 89148-2405
    - Las Vegas Cancer Center-Medical Center
  - Las Vegas, Nevada, United States, 89148
    - GenesisCare USA - Fort Apache
  - Las Vegas, Nevada, United States, 89149
    - HealthCare Partners Medical Group Oncology/Hematology-Centennial Hills
  - Las Vegas, Nevada, United States, 89128
    - Ann M Wierman MD LTD
  - Las Vegas, Nevada, United States, 89074
    - Las Vegas Urology - Pecos
  - Las Vegas, Nevada, United States, 89102
    - Desert West Surgery
  - Las Vegas, Nevada, United States, 89103
    - Hope Cancer Care of Nevada
  - Las Vegas, Nevada, United States, 89106
    - Urology Specialists of Nevada - Central
  - Las Vegas, Nevada, United States, 89113
    - Las Vegas Prostate Cancer Center
  - Las Vegas, Nevada, United States, 89113
    - Las Vegas Urology - Sunset
  - Las Vegas, Nevada, United States, 89128
    - Las Vegas Urology - Cathedral Rock
  - Las Vegas, Nevada, United States, 89128
    - Las Vegas Urology - Smoke Ranch
  - Las Vegas, Nevada, United States, 89128
    - Urology Specialists of Nevada - Northwest
  - Las Vegas, Nevada, United States, 89169
    - University Cancer Center
  - Las Vegas, Nevada, United States, 89113
    - Urology Specialists of Nevada - Southwest
  - Pahrump, Nevada, United States, 89048
    - Hope Cancer Care of Nevada-Pahrump
  - Reno, Nevada, United States, 89502
    - Renown Regional Medical Center
  - Reno, Nevada, United States, 89503
    - Saint Mary's Regional Medical Center
  - Reno, Nevada, United States, 89509
    - Radiation Oncology Associates
- New Jersey
  - Hackensack, New Jersey, United States, 07601
    - Hackensack University Medical Center
  - Lakewood, New Jersey, United States, 08701
    - Monmouth Medical Center Southern Campus
  - Long Branch, New Jersey, United States, 07740
    - Monmouth Medical Center
  - Morristown, New Jersey, United States, 07960
    - Morristown Medical Center
  - New Brunswick, New Jersey, United States, 08903
    - Rutgers Cancer Institute of New Jersey
  - New Brunswick, New Jersey, United States, 08903
    - Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital
- New Mexico
  - Albuquerque, New Mexico, United States, 87102
    - University of New Mexico Cancer Center
- New York
  - Albany, New York, United States, 12208
    - Albany Medical Center
  - Bronx, New York, United States, 10467
    - Montefiore Medical Center - Moses Campus
  - Buffalo, New York, United States, 14263
    - Roswell Park Cancer Institute
  - New York, New York, United States, 10065
    - Memorial Sloan Kettering Cancer Center
  - New York, New York, United States, 10029
    - Mount Sinai Hospital
  - New York, New York, United States, 10032
    - NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
  - New York, New York, United States, 10065
    - NYP/Weill Cornell Medical Center
  - New York, New York, United States, 10016
    - Laura and Isaac Perlmutter Cancer Center at NYU Langone
  - Stony Brook, New York, United States, 11794
    - Stony Brook University Medical Center
  - Syracuse, New York, United States, 13210
    - State University of New York Upstate Medical University
- North Carolina
  - Chapel Hill, North Carolina, United States, 27599
    - UNC Lineberger Comprehensive Cancer Center
  - Charlotte, North Carolina, United States, 28203
    - Carolinas Medical Center/Levine Cancer Institute
  - Clinton, North Carolina, United States, 28328
    - Southeastern Medical Oncology Center-Clinton
  - Goldsboro, North Carolina, United States, 27534
    - Southeastern Medical Oncology Center-Goldsboro
  - Goldsboro, North Carolina, United States, 27534
    - Wayne Memorial Hospital
  - Jacksonville, North Carolina, United States, 28546
    - Southeastern Medical Oncology Center-Jacksonville
  - Jacksonville, North Carolina, United States, 28546
    - Onslow Memorial Hospital
- North Dakota
  - Fargo, North Dakota, United States, 58103
    - Essentia Health Cancer Center-South University Clinic
  - Jamestown, North Dakota, United States, 58401
    - Essentia Health - Jamestown Clinic
- Ohio
  - Akron, Ohio, United States, 44308
    - Children's Hospital Medical Center of Akron
  - Cincinnati, Ohio, United States, 45229
    - Cincinnati Children's Hospital Medical Center
  - Cincinnati, Ohio, United States, 45220
    - Good Samaritan Hospital - Cincinnati
  - Cincinnati, Ohio, United States, 45242
    - Bethesda North Hospital
  - Cincinnati, Ohio, United States, 45247
    - TriHealth Cancer Institute-Westside
  - Cincinnati, Ohio, United States, 45255
    - TriHealth Cancer Institute-Anderson
  - Cleveland, Ohio, United States, 44109
    - MetroHealth Medical Center
  - Columbus, Ohio, United States, 43205
    - Nationwide Children's Hospital
- Oklahoma
  - Lawton, Oklahoma, United States, 73505
    - Cancer Centers of Southwest Oklahoma Research
  - Oklahoma City, Oklahoma, United States, 73104
    - University of Oklahoma Health Sciences Center
  - Oklahoma City, Oklahoma, United States, 73120
    - Mercy Hospital Oklahoma City
  - Tulsa, Oklahoma, United States, 74146
    - Oklahoma Cancer Specialists and Research Institute-Tulsa
- Oregon
  - Baker City, Oregon, United States, 97814
    - Saint Alphonsus Medical Center-Baker City
  - Bend, Oregon, United States, 97701
    - Saint Charles Health System
  - Clackamas, Oregon, United States, 97015
    - Clackamas Radiation Oncology Center
  - Clackamas, Oregon, United States, 97015
    - Providence Cancer Institute Clackamas Clinic
  - Coos Bay, Oregon, United States, 97420
    - Bay Area Hospital
  - Newberg, Oregon, United States, 97132
    - Providence Newberg Medical Center
  - Ontario, Oregon, United States, 97914
    - Saint Alphonsus Medical Center-Ontario
  - Oregon City, Oregon, United States, 97045
    - Providence Willamette Falls Medical Center
  - Portland, Oregon, United States, 97213
    - Providence Portland Medical Center
  - Portland, Oregon, United States, 97225
    - Providence Saint Vincent Medical Center
  - Redmond, Oregon, United States, 97756
    - Saint Charles Health System-Redmond
- Pennsylvania
  - Hershey, Pennsylvania, United States, 17033-0850
    - Penn State Milton S Hershey Medical Center
  - Philadelphia, Pennsylvania, United States, 19111
    - Fox Chase Cancer Center
  - Philadelphia, Pennsylvania, United States, 19104
    - Children's Hospital of Philadelphia
  - Philadelphia, Pennsylvania, United States, 19104
    - University of Pennsylvania/Abramson Cancer Center
- South Carolina
  - Boiling Springs, South Carolina, United States, 29316
    - Prisma Health Cancer Institute - Spartanburg
  - Columbia, South Carolina, United States, 29203
    - Prisma Health Richland Hospital
  - Easley, South Carolina, United States, 29640
    - Prisma Health Cancer Institute - Easley
  - Greenville, South Carolina, United States, 29605
    - Prisma Health Cancer Institute - Faris
  - Greenville, South Carolina, United States, 29607
    - Saint Francis Cancer Center
  - Greenville, South Carolina, United States, 29615
    - Prisma Health Cancer Institute - Eastside
  - Greenville, South Carolina, United States, 29605
    - Prisma Health Cancer Institute - Butternut
  - Greenville, South Carolina, United States, 29601
    - Saint Francis Hospital
  - Greenville, South Carolina, United States, 29605
    - BI-LO Charities Children's Cancer Center
  - Greenville, South Carolina, United States, 29605
    - Prisma Health Greenville Memorial Hospital
  - Greer, South Carolina, United States, 29650
    - Prisma Health Cancer Institute - Greer
  - Seneca, South Carolina, United States, 29672
    - Prisma Health Cancer Institute - Seneca
- Tennessee
  - Chattanooga, Tennessee, United States, 37404
    - Memorial Hospital
  - Hixson, Tennessee, United States, 37343
    - Pulmonary Medicine Center of Chattanooga-Hixson
  - Knoxville, Tennessee, United States, 37916
    - East Tennessee Childrens Hospital
  - Memphis, Tennessee, United States, 38105
    - Saint Jude Children's Research Hospital
  - Nashville, Tennessee, United States, 37232
    - Vanderbilt University/Ingram Cancer Center
  - Nashville, Tennessee, United States, 37203
    - The Children's Hospital at TriStar Centennial
  - Ooltewah, Tennessee, United States, 37363
    - Memorial GYN Plus
- Texas
  - Austin, Texas, United States, 78723
    - Dell Children's Medical Center of Central Texas
  - Bryan, Texas, United States, 77802
    - Saint Joseph Regional Cancer Center
  - Corpus Christi, Texas, United States, 78411
    - Driscoll Children's Hospital
  - El Paso, Texas, United States, 79905
    - El Paso Children's Hospital
  - Fort Worth, Texas, United States, 76104
    - Cook Children's Medical Center
  - San Antonio, Texas, United States, 78207
    - Children's Hospital of San Antonio
- Utah
  - American Fork, Utah, United States, 84003
    - American Fork Hospital / Huntsman Intermountain Cancer Center
  - Cedar City, Utah, United States, 84720
    - Sandra L Maxwell Cancer Center
  - Logan, Utah, United States, 84321
    - Logan Regional Hospital
  - Murray, Utah, United States, 84107
    - Intermountain Medical Center
  - Ogden, Utah, United States, 84403
    - McKay-Dee Hospital Center
  - Riverton, Utah, United States, 84065
    - Riverton Hospital
  - Saint George, Utah, United States, 84770
    - Saint George Regional Medical Center
  - Salt Lake City, Utah, United States, 84106
    - Utah Cancer Specialists-Salt Lake City
  - Salt Lake City, Utah, United States, 84143
    - LDS Hospital
- Virginia
  - Norfolk, Virginia, United States, 23507
    - Children's Hospital of The King's Daughters
- Washington
  - Aberdeen, Washington, United States, 98520
    - Providence Regional Cancer System-Aberdeen
  - Auburn, Washington, United States, 98001
    - MultiCare Auburn Medical Center
  - Bellevue, Washington, United States, 98004
    - Overlake Medical Center
  - Bellingham, Washington, United States, 98225
    - PeaceHealth Saint Joseph Medical Center
  - Bremerton, Washington, United States, 98310
    - Harrison HealthPartners Hematology and Oncology-Bremerton
  - Bremerton, Washington, United States, 98310
    - Harrison Medical Center
  - Burien, Washington, United States, 98166
    - Highline Medical Center-Main Campus
  - Centralia, Washington, United States, 98531
    - Providence Regional Cancer System-Centralia
  - Edmonds, Washington, United States, 98026
    - Swedish Cancer Institute-Edmonds
  - Enumclaw, Washington, United States, 98022
    - Saint Elizabeth Hospital
  - Everett, Washington, United States, 98201
    - Providence Regional Cancer Partnership
  - Federal Way, Washington, United States, 98003
    - Saint Francis Hospital
  - Gig Harbor, Washington, United States, 98335
    - MultiCare Gig Harbor Medical Park
  - Issaquah, Washington, United States, 98029
    - Swedish Cancer Institute-Issaquah
  - Kennewick, Washington, United States, 99336
    - Kadlec Clinic Hematology and Oncology
  - Lacey, Washington, United States, 98503
    - Providence Regional Cancer System-Lacey
  - Lakewood, Washington, United States, 98499
    - Saint Clare Hospital
  - Longview, Washington, United States, 98632
    - PeaceHealth Saint John Medical Center
  - Port Townsend, Washington, United States, 98368
    - Jefferson Healthcare
  - Poulsbo, Washington, United States, 98370
    - Harrison HealthPartners Hematology and Oncology-Poulsbo
  - Puyallup, Washington, United States, 98372
    - MultiCare Good Samaritan Hospital
  - Renton, Washington, United States, 98055
    - Valley Medical Center
  - Seattle, Washington, United States, 98105
    - Seattle Children's Hospital
  - Seattle, Washington, United States, 98107
    - Swedish Medical Center-Ballard Campus
  - Seattle, Washington, United States, 98122
    - Swedish Medical Center-First Hill
  - Seattle, Washington, United States, 98112
    - Kaiser Permanente Washington
  - Seattle, Washington, United States, 98104
    - Pacific Gynecology Specialists
  - Seattle, Washington, United States, 98122-5711
    - Swedish Medical Center-Cherry Hill
  - Sedro-Woolley, Washington, United States, 98284
    - PeaceHealth United General Medical Center
  - Shelton, Washington, United States, 98584
    - Providence Regional Cancer System-Shelton
  - Spokane, Washington, United States, 99204
    - Providence Sacred Heart Medical Center and Children's Hospital
  - Spokane, Washington, United States, 99204
    - MultiCare Deaconess Cancer and Blood Specialty Center - Downtown
  - Spokane, Washington, United States, 99218
    - MultiCare Deaconess Cancer and Blood Specialty Center - North
  - Spokane Valley, Washington, United States, 99216
    - MultiCare Deaconess Cancer and Blood Specialty Center - Valley
  - Tacoma, Washington, United States, 98405
    - Mary Bridge Children's Hospital and Health Center
  - Tacoma, Washington, United States, 98405
    - Northwest Medical Specialties PLLC
  - Tacoma, Washington, United States, 98431
    - Madigan Army Medical Center
  - Tacoma, Washington, United States, 98405
    - MultiCare Tacoma General Hospital
  - Tacoma, Washington, United States, 98405
    - Franciscan Research Center-Northwest Medical Plaza
  - Vancouver, Washington, United States, 98664
    - PeaceHealth Southwest Medical Center
  - Walla Walla, Washington, United States, 99362
    - Providence Saint Mary Regional Cancer Center
  - Yakima, Washington, United States, 98902
    - North Star Lodge Cancer Center at Yakima Valley Memorial Hospital
  - Yelm, Washington, United States, 98597
    - Providence Regional Cancer System-Yelm
- West Virginia
  - Bridgeport, West Virginia, United States, 26330
    - United Hospital Center
  - Martinsburg, West Virginia, United States, 25401
    - WVUH-Berkely Medical Center
  - Morgantown, West Virginia, United States, 26506
    - West Virginia University Healthcare
  - Parkersburg, West Virginia, United States, 26101
    - Camden Clark Medical Center
- Wisconsin
  - Ashland, Wisconsin, United States, 54806
    - Duluth Clinic Ashland
  - Ashland, Wisconsin, United States, 54806
    - Northwest Wisconsin Cancer Center
  - Burlington, Wisconsin, United States, 53105
    - Aurora Cancer Care-Southern Lakes VLCC
  - Chippewa Falls, Wisconsin, United States, 54729
    - Marshfield Clinic-Chippewa Center
  - Eau Claire, Wisconsin, United States, 54701
    - Marshfield Medical Center-EC Cancer Center
  - Fond Du Lac, Wisconsin, United States, 54937
    - Aurora Health Center-Fond du Lac
  - Germantown, Wisconsin, United States, 53022
    - Aurora Health Care Germantown Health Center
  - Grafton, Wisconsin, United States, 53024
    - Aurora Cancer Care-Grafton
  - Green Bay, Wisconsin, United States, 54311
    - Aurora BayCare Medical Center
  - Kenosha, Wisconsin, United States, 53142
    - Aurora Cancer Care-Kenosha South
  - La Crosse, Wisconsin, United States, 54601
    - Gundersen Lutheran Medical Center
  - Ladysmith, Wisconsin, United States, 54848
    - Marshfield Clinic - Ladysmith Center
  - Madison, Wisconsin, United States, 53792
    - University of Wisconsin Carbone Cancer Center
  - Marinette, Wisconsin, United States, 54143
    - Aurora Bay Area Medical Group-Marinette
  - Marshfield, Wisconsin, United States, 54449
    - Marshfield Medical Center-Marshfield
  - Milwaukee, Wisconsin, United States, 53226
    - Medical College of Wisconsin
  - Milwaukee, Wisconsin, United States, 53209
    - Aurora Cancer Care-Milwaukee
  - Milwaukee, Wisconsin, United States, 53215
    - Aurora Saint Luke's Medical Center
  - Milwaukee, Wisconsin, United States, 53233
    - Aurora Sinai Medical Center
  - Minocqua, Wisconsin, United States, 54548
    - Marshfield Clinic-Minocqua Center
  - Oshkosh, Wisconsin, United States, 54904
    - Vince Lombardi Cancer Clinic - Oshkosh
  - Racine, Wisconsin, United States, 53406
    - Aurora Cancer Care-Racine
  - Rice Lake, Wisconsin, United States, 54868
    - Marshfield Medical Center-Rice Lake
  - Sheboygan, Wisconsin, United States, 53081
    - Vince Lombardi Cancer Clinic-Sheboygan
  - Stevens Point, Wisconsin, United States, 54482
    - Marshfield Medical Center-River Region at Stevens Point
  - Summit, Wisconsin, United States, 53066
    - Aurora Medical Center in Summit
  - Two Rivers, Wisconsin, United States, 54241
    - Vince Lombardi Cancer Clinic-Two Rivers
  - Wausau, Wisconsin, United States, 54401
    - Marshfield Clinic-Wausau Center
  - Wauwatosa, Wisconsin, United States, 53226
    - Aurora Cancer Care-Milwaukee West
  - West Allis, Wisconsin, United States, 53227
    - Aurora West Allis Medical Center
  - Weston, Wisconsin, United States, 54476
    - Marshfield Medical Center - Weston
  - Wisconsin Rapids, Wisconsin, United States, 54494
    - Marshfield Clinic - Wisconsin Rapids Center
- Wyoming
  - Cheyenne, Wyoming, United States, 82001
    - Cheyenne Regional Medical Center-West
  - Cody, Wyoming, United States, 82414
    - Billings Clinic-Cody
  - Sheridan, Wyoming, United States, 82801
    - Welch Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

12 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

Description

Inclusion Criteria:

PHASE I (ARMS A, B, C, D, E, F, G, H, I, X, Y, Z)
Age >= 18 years
Patients must have pathologically confirmed relapsed or refractory classical Hodgkin lymphoma (cHL); a biopsy at any relapse is acceptable; other histologies including lymphocyte predominant (LP) HL are not permitted
Patients must have relapsed after first line chemotherapy; may have relapsed after autologous or allogeneic stem cell transplant, or have primary refractory disease; no upper limit for number of prior therapies; if status post allogeneic stem cell transplant, no active graft versus host disease
Patients may have received prior brentuximab vedotin, but must not have received brentuximab vedotin within 6 months prior to registration, and must not have relapsed within 6 months of receiving previous brentuximab vedotin; patients may not have received prior nivolumab or PD1/PDL1 axis agents; patients in the nivolumab/brentuximab cohorts ONLY (D, E, F, Y) may have received prior ipilimumab
Patients may have received other prior activating immunotherapies (i.e. checkpoint inhibitors), but must not have received them within 6 months prior to registration, and there must be no serious unresolved complication of therapy at the time of registration; for the purposes of this study monoclonal antibodies and antibody drug conjugates are not considered to be activating immunotherapies and there are no additional time restrictions on prior exposure to these agents (except prior brentuximab vedotin)
Eastern Cooperative Oncology Group (ECOG)-American College of Radiology Imaging Network (ACRIN) performance status between 0-2
Patients must have measurable disease; baseline measurements and evaluations must be obtained within 4 weeks of registration to the study; abnormal PET scans will not constitute evaluable disease unless verified by a diagnostic quality CT scan; patients must use the same imaging modality (CT or PET/CT) throughout the study
Patient must not be pregnant or breast-feeding due to risk of fetal harm by the chemotherapeutic agents prescribed in this protocol; all patients of childbearing potential must have a blood test or urine study within 2 weeks prior to registration to rule out pregnancy; a patient of childbearing potential is anyone, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)
Patient of childbearing potential and/or sexually active patients must either abstain from sexual intercourse for the duration of their participation in the study or agree to use both single barrier contraception and birth control pills or implants for at least one week prior to the start of the study drug and continuing for 5 months after the last dose of study drug (for patients of childbearing potential) and for 7 months after the last dose of study drug (for patients who are sexually active with anyone of childbearing potential); should a patient become pregnant or suspect pregnancy while the patient or their partner is participating in this study, the patient (or the participating partner) should inform the treating physician immediately
Patients must have no evidence of dyspnea at rest and a pulse oximetry > 92% while breathing room air
Patients must have forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) > 60% by pulmonary function test (PFT), unless due to large mediastinal mass from HL; carbon monoxide diffusion capacity (DLCO), FEV1, and FVC all > 50% predicted value; all pulmonary function tests must be obtained within one month prior to registration
Absolute neutrophil count (ANC) >= 1500/mcL (1.5 x 10^9/L) (obtained within 2 weeks prior to registration)
Platelets >= 75,000/mcL (75 x 10^9/L) (obtained within 2 weeks prior to registration)
Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 2.5 x upper limit of normal (ULN) (obtained within 2 weeks prior to registration)
Bilirubin =< 2 x upper limit of normal (ULN) (unless documented Gilbert's syndrome, for which bilirubin =< 3 x upper limit of normal [ULN] is permitted) (obtained within 2 weeks prior to registration)
Calculated creatinine clearance by Cockcroft-Gault formula >= 30 ml/min (obtained within 2 weeks prior to registration)
No evidence of prior malignancy except adequately treated non-melanoma skin cancer, in situ cervical carcinoma or any surgically- or radiation-cured malignancy continuously disease free for >= 5 years so as not to interfere with interpretation of radiographic response
Patient must have no current or prior history of central nervous system (CNS) involvement
All prior therapy must have been completed at least 21 days prior to enrollment; no concomitant anti lymphoma therapy, including systemic corticosteroids for the purpose of treatment of lymphoma are allowed; topical steroids are allowed
No history of Steven's Johnson's syndrome, toxic epidermal necrolysis (TEN)s syndrome, or motor neuropathy
Human immunodeficiency virus (HIV) positive patients are allowed on this study if they have a CD4 count > 400, and are on a stable antiviral regimen; patients with poorly controlled HIV or other chronic active viral infections will be excluded
Patients must not have autoimmune disorders or conditions of immunosuppression that require current ongoing treatment with systemic corticosteroids (or other systemic immunosuppressants), including oral steroids (i.e., prednisone, dexamethasone) or continuous use of topical steroid creams or ointments or ophthalmologic steroids; a history of occasional (but not continuous) use of steroid inhalers is allowed
- Replacement doses of steroids for patients with adrenal insufficiency are allowed; patients who discontinue use of these classes of medication for at least 2 weeks prior to initiation of study treatment are eligible if, in the judgment of the treating physician investigator, the patient is not likely to require resumption of treatment with these classes of drugs during the study
- Exclusion from this study also includes patients with a history of symptomatic autoimmune disease (e.g., rheumatoid arthritis, systemic progressive sclerosis [scleroderma], systemic lupus erythematosus, Sjogren's syndrome, autoimmune vasculitis [e.g., Wegener's Granulomatosis]); motor neuropathy considered of autoimmune origin (e.g., Guillain-Barre syndrome and Myasthenia Gravis); other CNS autoimmune disease (e.g., Multiple sclerosis); patients with autoimmune hypothyroid disease or type I diabetes on replacement treatment are eligible
Patients must not have grade 2 or greater peripheral sensory neuropathy
Patients must not have New York Heart Association (NYHA) class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia
Patients must not have previously existing hypersensitivity to brentuximab vedotin or ipilimumab
Patients must not have a serious medical or psychiatric illness likely to interfere with study participation
Patients must not be participating in any other clinical trial or taking any other experimental medications within 21 days prior to registration
Routine vaccinations, including seasonal influenza, should be given at least 2 weeks prior to study treatment; vaccines are not prohibited on study, but must be given at least 6 weeks after cycle 1 and not within 7 days of treatment
Patients registering to Arms D, E, F, G, H, I, X, Y must not currently be smoking tobacco or other substances and must not have smoked within the past 6 months
RANDOMIZED PHASE II (ARMS K AND L): Age >= 12 years
- Pediatric patients will include any patients < 18 years of age
RANDOMIZED PHASE II (ARMS K AND L): Patients must have pathologically confirmed relapsed or refractory classical Hodgkin lymphoma (cHL); a biopsy at any relapse is acceptable; other histologies including lymphocyte predominant (LP) HL are not permitted
RANDOMIZED PHASE II (ARMS K AND L): Patients must have relapsed after first line chemotherapy; may have relapsed after autologous stem cell transplant, or have primary refractory disease; no upper limit for number of prior therapies; patient must not have received a prior allogeneic stem cell transplant (out of risk of reactivation of pulmonary graft versus host disease [GVHD])
RANDOMIZED PHASE II (ARMS K AND L): Patients may have received prior brentuximab vedotin, but must not have received brentuximab vedotin within 6 months prior to registration, and must not have relapsed within 6 months of receiving previous brentuximab vedotin; patients may not have received prior nivolumab or PD1/PDL1 axis agents; patients may not have received prior ipilimumab
RANDOMIZED PHASE II (ARMS K AND L): Patients may not have received other prior activating immunotherapies (i.e. checkpoint inhibitor therapies); for the purposes of this study monoclonal antibodies and antibody drug conjugates are not considered to be activating immunotherapies and there are no additional time restrictions on prior exposure to these agents (except prior brentuximab vedotin)
RANDOMIZED PHASE II (ARMS K AND L): Adult patient (>= 18 years of age) ECOG-ACRIN performance status between 0-2
- Pediatric patients (16-17 years of age) must have a Karnofsky performance level >= 50%
- Pediatric patients (12-15 years of age) must have a Lansky performance level >= 50
RANDOMIZED PHASE II (ARMS K AND L): Patients must have measurable disease; baseline measurements and evaluations must be obtained within 4 weeks of registration to the study; abnormal PET scans will not constitute evaluable disease unless verified by a diagnostic quality CT scan; patients must use the same imaging modality (CT or PET/CT) throughout the study
RANDOMIZED PHASE II (ARMS K AND L): Patient must not be pregnant or breast-feeding due to risk of fetal harm by the chemotherapeutic agents prescribed in this protocol; all patients of childbearing potential must have a blood test or urine study within 2 weeks prior to registration to rule out pregnancy; a patient of childbearing potential is defined as anyone, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)
RANDOMIZED PHASE II (ARMS K AND L): Patient of childbearing potential and/or sexually active patient must either abstain from sexual intercourse for the duration of their participation in the study or agree to use both double barrier contraception and birth control pills or implants for at least one week prior to the start of the study drug and continuing for 5 months after the last dose of study drug (for patients of childbearing potential) and for 7 months after the last dose of study drug (for patients who are sexually active with anyone of childbearing potential); should a patient become pregnant or suspect pregnancy while the patient or their partner is participating in this study, the patient (or the participating partner) should inform the treating physician immediately
RANDOMIZED PHASE II (ARMS K AND L): Patients with impaired decision-making capacity are eligible with legally authorized representative
RANDOMIZED PHASE II (ARMS K AND L): Patients must have no evidence of dyspnea at rest and a pulse oximetry > 92% while breathing room air
RANDOMIZED PHASE II (ARMS K AND L): Patients must have FEV1/FVC > 60% by pulmonary function test (PFT), unless due to large mediastinal mass from HL; carbon monoxide diffusion capacity (DLCO), FEV1, and FVC all > 50% predicted value; all pulmonary function tests must be obtained within one month prior to registration
RANDOMIZED PHASE II (ARMS K AND L): ANC >= 1500/mcL (1.5 x 0^9/L) (obtained within 2 weeks prior to registration)
RANDOMIZED PHASE II (ARMS K AND L): Platelets >= 75,000/mcL (75 x 10^9/L) (obtained within 2 weeks prior to registration)
RANDOMIZED PHASE II (ARMS K AND L): AST/ALT =< 2.5 x upper limit of normal (ULN) for age (obtained within 2 weeks prior to registration)
RANDOMIZED PHASE II (ARMS K AND L): Bilirubin =< 2 x upper limit of normal (ULN) (unless documented Gilbert's syndrome, for which bilirubin =< 3 x upper limit of normal [ULN] is permitted) (obtained within 2 weeks prior to registration)
RANDOMIZED PHASE II (ARMS K AND L): Adult patients (>= 18 years old) must have a calculated creatinine clearance by Cockcroft-Gault formula >= 30 ml/min (obtained within 2 weeks prior to registration)
RANDOMIZED PHASE II (ARMS K AND L): Pediatric patients (< 18 years old) must have a creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min/1.73 m^2 or serum creatinine based on age/gender as follows:
- Age: maximum serum creatinine (mg/dL)
  - < 13 years: male (1.2), female (1.2)
  - 13 to < 16 years: male (1.5), female (1.4)
  - >= 16 years: male (1.7), female (1.4)
RANDOMIZED PHASE II (ARMS K AND L): No evidence of prior malignancy except adequately treated non-melanoma skin cancer, in situ cervical carcinoma or any surgically- or radiation-cured malignancy continuously disease free for >= 5 years so as not to interfere with interpretation of radiographic response
RANDOMIZED PHASE II (ARMS K AND L): Patient must have no current or prior history of CNS involvement
RANDOMIZED PHASE II (ARMS K AND L): All prior therapy must have been completed at least 21 days prior to enrollment (6 weeks for nitrosoureas or mitomycin C); no concomitant anti lymphoma therapy, including systemic corticosteroids for the purpose of treatment of lymphoma are allowed; topical steroids are allowed
RANDOMIZED PHASE II (ARMS K AND L): No history of Steven's Johnson's syndrome, TENs syndrome, or motor neuropathy
RANDOMIZED PHASE II (ARMS K AND L): HIV positive patients are eligible provided they meet the other protocol criteria including the following:
- Long term survival expected were it not for the cHL
- HIV viral loads undetectable by standard clinical HIV testing
- Willing to adhere to effective combination antiretroviral therapy
RANDOMIZED PHASE II (ARMS K AND L): Patients must not have autoimmune disorders, prior solid organ transplant, or conditions of immunosuppression that require current ongoing treatment with systemic corticosteroids (or other systemic immunosuppressants), including oral steroids (i.e., prednisone, dexamethasone) or continuous use of topical steroid creams or ointments or ophthalmologic steroids; a history of occasional (but not continuous) use of steroid inhalers is allowed; replacement doses of steroids for patients with adrenal insufficiency are allowed; patients who discontinue use of steroid medication for at least 2 weeks prior to initiation of therapy are eligible if, in the judgment of the treating physician investigator, the patient is not likely to require resumption of treatment with these classes of drugs during the study; exclusion from this study also includes patients with a history of symptomatic autoimmune disease (e.g., rheumatoid arthritis, systemic progressive sclerosis [scleroderma], systemic lupus erythematosus, Sjogren's syndrome, autoimmune vasculitis [e.g., Wegener's Granulomatosis]); motor neuropathy considered of autoimmune origin (e.g., Guillain-Barre syndrome and Myasthenia Gravis); other CNS autoimmune disease (e.g., Multiple sclerosis); patients with autoimmune hypothyroid disease or type I diabetes on replacement treatment are eligible
RANDOMIZED PHASE II (ARMS K AND L): Patients must not have grade 2 or greater peripheral sensory neuropathy
RANDOMIZED PHASE II (ARMS K AND L): Patients must not have NYHA class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia
RANDOMIZED PHASE II (ARMS K AND L): Patients must not have previously existing hypersensitivity to brentuximab vedotin or ipilimumab
RANDOMIZED PHASE II (ARMS K AND L): Patients must not have a serious medical or psychiatric illness likely to interfere with study participation
RANDOMIZED PHASE II (ARMS K AND L): Patients must not be participating in any other clinical trial or taking any other experimental medications within 21 days prior to registration
RANDOMIZED PHASE II (ARMS K AND L): Routine vaccinations, including seasonal influenza, should be given at least 2 weeks prior to study treatment; vaccines are not prohibited on study, but must be given at least 6 weeks after cycle 1 and not within 7 days of treatment
RANDOMIZED PHASE II (ARMS K AND L): Patients must not currently be smoking tobacco or other agents; vaping is not allowed
RANDOMIZED PHASE II (ARMS K AND L): Patients must not have a history of or evidence of cardiovascular risks including any of the following:
- QT interval corrected for heart rate using the Bazett's formula QTcB >= 480 msec at baseline
- History of acute coronary syndromes (including myocardial infarction or unstable angina), coronary angioplasty, or stenting within the past 24 weeks prior to registration
- History prior to registration or evidence of current >= class II congestive heart failure as defined by the New York Heart Association (NYHA) functional classification system
- Left ventricular ejection fraction (LVEF) =< lower limit of normal on cardiac echocardiogram (echo) or multigated acquisition scan (MUGA)
- Intra-cardiac defibrillator
- History of abnormal cardiac valve morphology (>= grade 2) documented by ECHO; (subjects with grade 1 abnormalities [i.e., mild regurgitation/stenosis] can be entered on study); subjects with moderate valvular thickening should not be entered on study
- History or evidence of current clinically significant uncontrolled cardiac arrhythmias; clarification: subjects with atrial fibrillation controlled for > 30 days prior to dosing are eligible
- Treatment refractory hypertension defined as a blood pressure of systolic > 140 mmHg and/or diastolic > 90 mm Hg which cannot be controlled by anti-hypertensive therapy

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Interventional Model: Parallel Assignment
Masking: None (Open Label)

Number of Arms

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phase I Arm I (brentuximab vedotin, ipilimumab) Patients receive brentuximab vedotin IV over 30 minutes on day 1 of cycles 1-16 and ipilimumab IV over 90 minutes on day 1 of cycles 1-4, 8, 12, and 16. Treatment repeats every 21 days for up to 16 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or PET scan throughout the trial. Patients undergo blood sample collection and may undergo tumor biopsy on study.	Procedure: Biospecimen Collection Undergo collection of blood Other Names: Biological Sample Collection Biospecimen Collected Specimen Collection Biological: Ipilimumab Given IV Other Names: Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody BMS-734016 Ipilimumab Biosimilar CS1002 MDX-010 MDX-CTLA4 Yervoy Procedure: Computed Tomography Undergo CT Other Names: CT CAT CAT Scan Computed Axial Tomography Computerized Axial Tomography Computerized Tomography CT Scan tomography Computerized axial tomography (procedure) Computerized Tomography (CT) scan Drug: Brentuximab Vedotin Given IV Other Names: Adcetris SGN-35 cAC10-vcMMAE ADC SGN-35 Anti-CD30 Antibody-Drug Conjugate SGN-35 Anti-CD30 Monoclonal Antibody-MMAE SGN-35 Anti-CD30 Monoclonal Antibody-Monomethylauristatin E SGN-35 Procedure: Positron Emission Tomography Undergo PET Other Names: Medical Imaging, Positron Emission Tomography PET PET Scan Positron Emission Tomography Scan Positron-Emission Tomography proton magnetic resonance spectroscopic imaging PT Positron emission tomography (procedure) Procedure: Biopsy Undergo biopsy Other Names: Bx BIOPSY_TYPE
Experimental: Phase I Arm II (brentuximab vedotin, nivolumab) Patients receive brentuximab vedotin IV over 90 minutes on day 1 of cycles 1-16 and nivolumab IV over 30 minutes on day 1 of cycles 1-46. Treatment repeats every 21 days for up to 16 cycles and every 14 days beginning cycle 17 for up to 46 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or PET scan throughout the trial. Patients undergo blood sample collection and may undergo tumor biopsy on study.	Biological: Nivolumab Given IV Other Names: BMS-936558 MDX-1106 NIVO ONO-4538 Opdivo CMAB819 Nivolumab Biosimilar CMAB819 ABP 206 Nivolumab Biosimilar ABP 206 BCD-263 Nivolumab Biosimilar BCD-263 Procedure: Biospecimen Collection Undergo collection of blood Other Names: Biological Sample Collection Biospecimen Collected Specimen Collection Procedure: Computed Tomography Undergo CT Other Names: CT CAT CAT Scan Computed Axial Tomography Computerized Axial Tomography Computerized Tomography CT Scan tomography Computerized axial tomography (procedure) Computerized Tomography (CT) scan Drug: Brentuximab Vedotin Given IV Other Names: Adcetris SGN-35 cAC10-vcMMAE ADC SGN-35 Anti-CD30 Antibody-Drug Conjugate SGN-35 Anti-CD30 Monoclonal Antibody-MMAE SGN-35 Anti-CD30 Monoclonal Antibody-Monomethylauristatin E SGN-35 Procedure: Positron Emission Tomography Undergo PET Other Names: Medical Imaging, Positron Emission Tomography PET PET Scan Positron Emission Tomography Scan Positron-Emission Tomography proton magnetic resonance spectroscopic imaging PT Positron emission tomography (procedure) Procedure: Biopsy Undergo biopsy Other Names: Bx BIOPSY_TYPE
Experimental: Phase I Arm III (brentuximab vedotin, nivolumab, ipilimumab) Patients receive brentuximab vedotin IV over 90 minutes on day 1 of cycles 1-16, nivolumab IV over 30 minutes on day 1 of cycles 1-46, and ipilimumab IV over 30 minutes on day 1 every 12 weeks for up to 9 doses. Treatment repeats every 21 days for up to 16 cycles and every 14 days beginning cycle 17 for up to 46 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or PET scan throughout the trial. Patients undergo blood sample collection and may undergo tumor biopsy on study.	Biological: Nivolumab Given IV Other Names: BMS-936558 MDX-1106 NIVO ONO-4538 Opdivo CMAB819 Nivolumab Biosimilar CMAB819 ABP 206 Nivolumab Biosimilar ABP 206 BCD-263 Nivolumab Biosimilar BCD-263 Procedure: Biospecimen Collection Undergo collection of blood Other Names: Biological Sample Collection Biospecimen Collected Specimen Collection Biological: Ipilimumab Given IV Other Names: Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody BMS-734016 Ipilimumab Biosimilar CS1002 MDX-010 MDX-CTLA4 Yervoy Procedure: Computed Tomography Undergo CT Other Names: CT CAT CAT Scan Computed Axial Tomography Computerized Axial Tomography Computerized Tomography CT Scan tomography Computerized axial tomography (procedure) Computerized Tomography (CT) scan Drug: Brentuximab Vedotin Given IV Other Names: Adcetris SGN-35 cAC10-vcMMAE ADC SGN-35 Anti-CD30 Antibody-Drug Conjugate SGN-35 Anti-CD30 Monoclonal Antibody-MMAE SGN-35 Anti-CD30 Monoclonal Antibody-Monomethylauristatin E SGN-35 Procedure: Positron Emission Tomography Undergo PET Other Names: Medical Imaging, Positron Emission Tomography PET PET Scan Positron Emission Tomography Scan Positron-Emission Tomography proton magnetic resonance spectroscopic imaging PT Positron emission tomography (procedure) Procedure: Biopsy Undergo biopsy Other Names: Bx BIOPSY_TYPE
Experimental: Phase II Arm I (brentuximab vedotin, nivolumab) Patients receive brentuximab vedotin IV over 90 minutes on day 1 of cycles 1-16 and nivolumab IV over 30 minutes on day 1 of cycles 1-34. Treatment repeats every 21 days for up to 34 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or PET scan throughout the trial. Patients undergo blood sample collection and may undergo tumor biopsy on study.	Biological: Nivolumab Given IV Other Names: BMS-936558 MDX-1106 NIVO ONO-4538 Opdivo CMAB819 Nivolumab Biosimilar CMAB819 ABP 206 Nivolumab Biosimilar ABP 206 BCD-263 Nivolumab Biosimilar BCD-263 Procedure: Biospecimen Collection Undergo collection of blood Other Names: Biological Sample Collection Biospecimen Collected Specimen Collection Procedure: Computed Tomography Undergo CT Other Names: CT CAT CAT Scan Computed Axial Tomography Computerized Axial Tomography Computerized Tomography CT Scan tomography Computerized axial tomography (procedure) Computerized Tomography (CT) scan Drug: Brentuximab Vedotin Given IV Other Names: Adcetris SGN-35 cAC10-vcMMAE ADC SGN-35 Anti-CD30 Antibody-Drug Conjugate SGN-35 Anti-CD30 Monoclonal Antibody-MMAE SGN-35 Anti-CD30 Monoclonal Antibody-Monomethylauristatin E SGN-35 Procedure: Positron Emission Tomography Undergo PET Other Names: Medical Imaging, Positron Emission Tomography PET PET Scan Positron Emission Tomography Scan Positron-Emission Tomography proton magnetic resonance spectroscopic imaging PT Positron emission tomography (procedure) Procedure: Biopsy Undergo biopsy Other Names: Bx BIOPSY_TYPE
Experimental: Phase II Arm II (brentuximab vedotin, nivolumab, ipilimumab) Patients receive brentuximab vedotin IV over 90 minutes on day 1 of cycles 1-16, nivolumab IV over 30 minutes on day 1 of cycles 1-34, and ipilimumab IV over 30 minutes on day 1 every 12 weeks for up to 9 doses. Treatment repeats every 21 days for up to 34 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or PET scan throughout the trial. Patients undergo blood sample collection and may undergo tumor biopsy on study.	Biological: Nivolumab Given IV Other Names: BMS-936558 MDX-1106 NIVO ONO-4538 Opdivo CMAB819 Nivolumab Biosimilar CMAB819 ABP 206 Nivolumab Biosimilar ABP 206 BCD-263 Nivolumab Biosimilar BCD-263 Procedure: Biospecimen Collection Undergo collection of blood Other Names: Biological Sample Collection Biospecimen Collected Specimen Collection Biological: Ipilimumab Given IV Other Names: Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody BMS-734016 Ipilimumab Biosimilar CS1002 MDX-010 MDX-CTLA4 Yervoy Procedure: Computed Tomography Undergo CT Other Names: CT CAT CAT Scan Computed Axial Tomography Computerized Axial Tomography Computerized Tomography CT Scan tomography Computerized axial tomography (procedure) Computerized Tomography (CT) scan Drug: Brentuximab Vedotin Given IV Other Names: Adcetris SGN-35 cAC10-vcMMAE ADC SGN-35 Anti-CD30 Antibody-Drug Conjugate SGN-35 Anti-CD30 Monoclonal Antibody-MMAE SGN-35 Anti-CD30 Monoclonal Antibody-Monomethylauristatin E SGN-35 Procedure: Positron Emission Tomography Undergo PET Other Names: Medical Imaging, Positron Emission Tomography PET PET Scan Positron Emission Tomography Scan Positron-Emission Tomography proton magnetic resonance spectroscopic imaging PT Positron emission tomography (procedure) Procedure: Biopsy Undergo biopsy Other Names: Bx BIOPSY_TYPE

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum tolerated dose (MTD) of each combination (Phase I) Time Frame: 21 days	MTD defined as the highest dose level at which less than 33% of 6 patients experience a dose limiting toxicity, will be graded by the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Upon completion of the trial, frequency of subjects experiencing toxicities will be tabulated. Toxicities will be assessed and graded according to CTCAE version 4.0 terminology. Exact 95% confidence intervals (CI) around the toxicity proportions will be calculated.	21 days
CR rate (Phase II) Time Frame: Up to 10 years	The analysis of CR between two arms will be performed using exact Cochran-Mantel-Haenszel (CMH) test stratifying on prior brentuximab vedotin (BV) (yes versus [vs.] no) and age (< 18 vs. >= 18). Multivariable logistic regression modeling will be used to adjust for the effect of any covariates that are associated with these categorical outcomes.	Up to 10 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete response (CR) rate (Phase I) Time Frame: Up to 3 years	Assessed using the Revised Response Criteria for Malignant Lymphoma and reported along with the 95% CI.	Up to 3 years
Partial response (PR) rate (Phase I) Time Frame: Up to 3 years	Assessed using the Revised Response Criteria for Malignant Lymphoma and reported along with the 95% CI.	Up to 3 years
Overall response rate (ORR) rate (Phase I) Time Frame: Up to 3 years	Assessed using the Revised Response Criteria for Malignant Lymphoma and reported along with the 95% CI.	Up to 3 years
Duration of response (DOR) (Phase I) Time Frame: From the documented beginning of response up to 3 years	DOR will be estimated using Kaplan-Meier methodology. Greenwood's formula will be used to calculate 95% CI for the Kaplan-Meier estimates. Descriptive statistics will be used to evaluate the DOR achieved with the protocol therapy and with the most recent prior systemic therapy.	From the documented beginning of response up to 3 years
Overall survival (OS) (Phase I) Time Frame: From the date of study entry up to 3 years	OS will be estimated using Kaplan-Meier methodology. Greenwood's formula will be used to calculate 95% CI for the Kaplan-Meier estimates.	From the date of study entry up to 3 years
Progression-free survival (PFS) (Phase I) Time Frame: From entry onto study up to 3 years	PFS will be estimated using Kaplan-Meier methodology. Greenwood's formula will be used to calculate 95% CI for the Kaplan-Meier estimates.	From entry onto study up to 3 years
ORR (Phase II) Time Frame: Up to 10 years	Assessed using Revised Response (Cheson) and Deauville criteria. The analysis of ORR between two arms will be performed using the CMH test stratifying on prior BV (yes vs. no) and age (< 18 vs. >= 18). Multivariable logistic regression modeling will be used to adjust for the effect of any covariates that are associated with these categorical outcomes.	Up to 10 years
PFS (or modified PFS) (Phase II) Time Frame: From randomization up to 10 years	PFS will be estimated using Kaplan-Meier methodology and compared between arms using stratified log-rank test. Greenwood's formula will be used to calculate 95% confidence intervals for the Kaplan-Meier estimates. Cox proportional regression model will be used to estimate hazard ratios (95% CI) and assess the relationship between other prognostic factors with time-to-event outcome. Point estimates of all endpoints will be accompanied by the corresponding 95% confidence intervals.	From randomization up to 10 years
OS (Phase II) Time Frame: From randomization up to 10 years	OS will be estimated using Kaplan-Meier methodology and compared between arms using stratified log-rank test. Greenwood's formula will be used to calculate 95% confidence intervals for the Kaplan-Meier estimates. Cox proportional regression model will be used to estimate hazard ratios (95% CI) and assess the relationship between other prognostic factors with time-to-event outcome. Point estimates of all endpoints will be accompanied by the corresponding 95% confidence intervals.	From randomization up to 10 years
DOR (Phase II) Time Frame: From the documented beginning of response up to 10 years	DOR, will be estimated using Kaplan-Meier methodology and compared between arms using stratified log-rank test. Greenwood's formula will be used to calculate 95% confidence intervals for the Kaplan-Meier estimates. Cox proportional regression model will be used to estimate hazard ratios (95% CI) and assess the relationship between other prognostic factors with time-to-event outcome. Point estimates of all endpoints will be accompanied by the corresponding 90% confidence intervals. The DOR achieved with the most recent prior systemic therapy will be collected on the case report forms, and descriptive statistics will be used to evaluate the DOR achieved with the protocol therapy and with the most recent prior systemic therapy.	From the documented beginning of response up to 10 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in the percentage of activated T cells and natural killer cells (Phase I and II) Time Frame: Baseline (Time 1) to 9 weeks (Time 3, time of first re-staging)	These quantities of interest will be calculated for each patient and the Wilcoxon signed-rank test will be used to test for significant difference between the time points. Using Wilcoxon rank sum test (two-sided type I error of 0.1), differences between those who progress or die within one year versus (vs.) those who are event-free at one year will be evaluated.	Baseline (Time 1) to 9 weeks (Time 3, time of first re-staging)
Change in the percentages of activated T cells and natural killer cells (Phase I and II) Time Frame: Day 1 of cycle 2 (Time 2) or 9 weeks (Time 3) to up to 6 weeks after completion of study treatment (Time 4, end of study)	These quantities of interest will be calculated for each patient and the Wilcoxon signed-rank test will be used to test for significant difference between the time points. Using the Wilcoxon rank sum test (two-sided type I error of 0.1), differences between those who progress or die within one year vs. those who are event-free at one year will be evaluated.	Day 1 of cycle 2 (Time 2) or 9 weeks (Time 3) to up to 6 weeks after completion of study treatment (Time 4, end of study)
Effects of combinations on systemic immunity (Phase I and II) Time Frame: Baseline to up to 6 weeks after completion of study treatment		Baseline to up to 6 weeks after completion of study treatment
Pre- and post-treatment levels of cytokines and T cell specific biomarkers (Phase I and II) Time Frame: Baseline to up to 6 weeks after completion of study treatment	Pre- and post-treatment levels of these markers will be compared using the Wilcoxon signed-rank test with two-sided type I error of 0.1. Marker levels between patients who fail at 1-year vs. patients who are event-free at 1-year will be evaluated. Given limited data, the analyses of PD-1, co-expression of Tim-3 with PD-1, ICOS, sCD30, galectin-1 and the peripheral blood absolute lymphocyte to monocyte ratio will be mainly exploratory and will be summarized descriptively at the time-points described above. The association with PFS will be explored.	Baseline to up to 6 weeks after completion of study treatment
Differentially expressed genes between two groups (patients who fail at 1-year vs. patients who are event-free at 1-year or responders vs. non-responders) (Phase I and II) Time Frame: 1 year	Assessed using gene expression profiling (GEP). Differentially expressed genes will be identified using a rank-based method developed by Dr. Hong (RankProd, R package, Bioconductor Project) with multiple comparison adjustment using a false discovery rate approach. A two-way unsupervised hierarchical clustering analysis will be applied to both the genes and the samples to illustrate whether GEP can separate two groups or is associated with other clinical factors. The genes ranked as most significant will be assessed by gene ontology and pathway analysis for their potential functions in lymphoma biology and treatment failure.	1 year
Absolute maximum standard uptake value (SUVmax) (Phase II) Time Frame: Up to cycle 10	Image data will be evaluated using Lugano response criteria with various D 5PS cut-offs in the entire cohort and in different therapy cohorts to determine if the existing set of criteria is sufficient to segregate the group into various response categories. Will correlate PFS, event free survival (EFS), OS 5PS in two reading settings (1-3 [negative] vs 4-5 [positive] and D 5PS 1-4 [negative] vs 5 [positive]) (Kaplan-Meier [KM] curve and log-rank testing).	Up to cycle 10
Metabolic whole body tumor volume (MTV) and tumor lesion glycolysis (TLG) Time Frame: Up to cycle 10	Image data will be evaluated using Lugano response criteria with various D 5PS cut-offs in the entire cohort and in different therapy cohorts to determine if the existing set of criteria is sufficient to segregate the group into various response categories. Will correlate PFS, EFS, OS 5PS in two reading settings (1-3 [negative] vs 4-5 [positive] and D 5PS 1-4 [negative] vs 5 [positive]) (KM curve and log-rank testing).	Up to cycle 10
Percent change in SUVmax, MTV and TLG between baseline and during therapy Time Frame: Baseline up to cycle 10	Image data will be evaluated using Lugano response criteria with various D 5PS cut-offs in the entire cohort and in different therapy cohorts to determine if the existing set of criteria is sufficient to segregate the group into various response categories. Will correlate PFS, EFS, OS 5PS in two reading settings (1-3 [negative] vs 4-5 [positive] and D 5PS 1-4 [negative] vs 5 [positive]) (KM curve and log-rank testing).	Baseline up to cycle 10
Percent change in size (sum of perpendicular diameters [SPD]) on computed tomography (CT) Time Frame: Baseline up to cycle 10	Image data will be evaluated using Lugano response criteria with various D 5PS cut-offs in the entire cohort and in different therapy cohorts to determine if the existing set of criteria is sufficient to segregate the group into various response categories. Will correlate PFS, EFS, OS 5PS in two reading settings (1-3 [negative] vs 4-5 [positive] and D 5PS 1-4 [negative] vs 5 [positive]) (KM curve and log-rank testing).	Baseline up to cycle 10
Absolute CT tumor volumes Time Frame: Up to cycle 10	Image data will be evaluated using Lugano response criteria with various D 5PS cut-offs in the entire cohort and in different therapy cohorts to determine if the existing set of criteria is sufficient to segregate the group into various response categories. Will correlate PFS, EFS, OS 5PS in two reading settings (1-3 [negative] vs 4-5 [positive] and D 5PS 1-4 [negative] vs 5 [positive]) (KM curve and log-rank testing).	Up to cycle 10
Percent change in CT size (SPD) and in CT tumor volume between baseline and during therapy Time Frame: Baseline up to cycle 10	Image data will be evaluated using Lugano response criteria with various D 5PS cut-offs in the entire cohort and in different therapy cohorts to determine if the existing set of criteria is sufficient to segregate the group into various response categories. Will correlate PFS, EFS, OS 5PS in two reading settings (1-3 [negative] vs 4-5 [positive] and D 5PS 1-4 [negative] vs 5 [positive]) (KM curve and log-rank testing).	Baseline up to cycle 10
Microbiome analysis (Phase I and II) Time Frame: Completion of study treatment	Will compare the gut microbiome between Hodgkin lymphoma (HL) patients and healthy controls with respect to global diversity, taxonomic abundance, and bacterial functional pathways. The relative abundance of each taxon (phyla to genera) and functional pathways among different groups will be statistically compared in univariate analysis using t-test (or Wilcoxon test) and in multivariate analysis using logistic regression. Global diversity tests and multivariate analysis for taxonomic abundance and functional pathways will be adjusted for potential confounders (age, gender, race, and body mass index) in the comparisons of HL patients and controls, and further adjusted for stage and grade when examining the clinical response among HL patients.	Completion of study treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Cancer Institute (NCI)

Investigators

Principal Investigator: Catherine S Diefenbach, ECOG-ACRIN Cancer Research Group

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Diefenbach CS, Hong F, Ambinder RF, Cohen JB, Robertson MJ, David KA, Advani RH, Fenske TS, Barta SK, Palmisiano ND, Svoboda J, Morgan DS, Karmali R, Sharon E, Streicher H, Kahl BS, Ansell SM. Ipilimumab, nivolumab, and brentuximab vedotin combination therapies in patients with relapsed or refractory Hodgkin lymphoma: phase 1 results of an open-label, multicentre, phase 1/2 trial. Lancet Haematol. 2020 Sep;7(9):e660-e670. doi: 10.1016/S2352-3026(20)30221-0.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 7, 2014

Primary Completion (Estimated)

March 20, 2025

Study Completion (Estimated)

March 20, 2025

Study Registration Dates

First Submitted

July 8, 2013

First Submitted That Met QC Criteria

July 8, 2013

First Posted (Estimated)

July 11, 2013

Study Record Updates

Last Update Posted (Actual)

April 16, 2024

Last Update Submitted That Met QC Criteria

April 13, 2024

Last Verified

March 1, 2024

More Information

Terms related to this study

Other Study ID Numbers

NCI-2013-01275 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
U10CA180820 (U.S. NIH Grant/Contract)
U24CA196172 (U.S. NIH Grant/Contract)
E4412 (Other Identifier: CTEP)
S14-00011

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Clinical Trials on Recurrent Classic Hodgkin Lymphoma

Guangzhou Gloria Biosciences Co., Ltd.

Not yet recruiting

GLS-010 Monotherapy Versus Chemotherapy in Patients With Relapsed or Refractory Classical Hodgkin's Lymphoma (R/R cHL)

Recurrent Classic Hodgkin Lymphoma | Refractory Classic Hodgkin Lymphoma | Classic Hodgkin's Lymphoma
City of Hope Medical Center
National Cancer Institute (NCI)

Recruiting

CC-486 and Nivolumab for the Treatment of Hodgkin Lymphoma Refractory to PD-1 Therapy or Relapsed

Recurrent Classic Hodgkin Lymphoma | Refractory Classic Hodgkin Lymphoma

United States
National Cancer Institute (NCI)

Withdrawn

A Trial Comparing Chemotherapy Versus Novel Immune Checkpoint Inhibitor (Pembrolizumab) Plus Chemotherapy in Treating Relapsed/Refractory Classical Hodgkin Lymphoma

Recurrent Classic Hodgkin Lymphoma | Refractory Classic Hodgkin Lymphoma
Emory University
National Cancer Institute (NCI)

Recruiting

Brentuximab Vedotin and Nivolumab for the Treatment of Relapsed/Refractory Classic Hodgkin Lymphoma Previously Treated With Brentuximab Vedotin or Checkpoint Inhibitors

Recurrent Classic Hodgkin Lymphoma | Refractory Classic Hodgkin Lymphoma

United States
M.D. Anderson Cancer Center
National Cancer Institute (NCI)

Completed

Combination Chemotherapy With or Without Bortezomib in Treating Patients With Classical Hodgkin Lymphoma That Has Returned or Does Not Respond to Prior Treatment.

Recurrent Classic Hodgkin Lymphoma | Refractory Classic Hodgkin Lymphoma

United States
City of Hope Medical Center
National Cancer Institute (NCI)

Active, not recruiting

Pembrolizumab and Vorinostat in Patients With Relapsed or Refractory DLBCL, FCL or HL.

Recurrent Grade 1 Follicular Lymphoma | Recurrent Grade 2 Follicular Lymphoma | Recurrent Diffuse Large B-Cell Lymphoma | Refractory Diffuse Large B-Cell Lymphoma | Recurrent Transformed Non-Hodgkin Lymphoma | Recurrent Grade 3a Follicular Lymphoma | Recurrent Classic Hodgkin Lymphoma | Refractory... and other conditions

United States
National Cancer Institute (NCI)

Active, not recruiting

Immunotherapy (Nivolumab or Brentuximab Vedotin) Plus Combination Chemotherapy in Treating Patients With Newly Diagnosed Stage III-IV Classic Hodgkin Lymphoma

Ann Arbor Stage III Hodgkin Lymphoma | Ann Arbor Stage III Lymphocyte-Depleted Classic Hodgkin Lymphoma | Ann Arbor Stage III Mixed Cellularity Classic Hodgkin Lymphoma | Ann Arbor Stage III Nodular Sclerosis Classic Hodgkin Lymphoma | Ann Arbor Stage IV Hodgkin Lymphoma | Ann Arbor Stage IV... and other conditions

United States, Canada, Puerto Rico
City of Hope Medical Center
National Cancer Institute (NCI)

Active, not recruiting

Brentuximab Vedotin and Nivolumab in Treating Patients With Early Stage Classic Hodgkin Lymphoma

Classic Hodgkin Lymphoma | Lymphocyte-Rich Classic Hodgkin Lymphoma | Ann Arbor Stage IB Hodgkin Lymphoma | Ann Arbor Stage II Hodgkin Lymphoma | Ann Arbor Stage IIA Hodgkin Lymphoma | Ann Arbor Stage IIB Hodgkin Lymphoma | Ann Arbor Stage I Hodgkin Lymphoma | Ann Arbor Stage I Mixed Cellularity... and other conditions

United States
City of Hope Medical Center
National Cancer Institute (NCI)

Active, not recruiting

Nivolumab & Brentuximab Vedotin Consolidation After Autologous SCT in Patients With High-Risk Classical Hodgkin Lymphoma

Recurrent Hodgkin Lymphoma | Refractory Hodgkin Lymphoma | Classic Hodgkin Lymphoma

United States
Stanford University
Merck Sharp & Dohme LLC

Recruiting

Study of Magrolimab and Pembrolizumab in Relapsed or Refractory Classic Hodgkin Lymphoma

Hodgkin Lymphoma | Classic Hodgkin Lymphoma | Refractory Classic Hodgkin Lymphoma | Relapsed Classical Hodgkin Lymphoma

United States

Clinical Trials on Nivolumab

Universitair Ziekenhuis Brussel

Not yet recruiting

A Clinical Trial on Combined (Neo-)Adjuvant Intravenous Plus Intracranial Administration of Ipilimumab and Nivolumab in Recurrent Glioblastoma (NEO-GLITIPNI)

Recurrent Glioblastoma

Belgium
Brown University
Bristol-Myers Squibb; The Miriam Hospital; Rhode Island Hospital; Women and Infants...

Terminated

BrUOG 355: Nivolumab to Tailored Radiation Therapy With Concomitant Cisplatin in the Treatment of Patients With Cervical Cancer

Cervical Cancer

United States
Bristol-Myers Squibb

Recruiting

A Study to Evaluate Whether Participants With Melanoma Prefer Subcutaneous vs Intravenous Administration of Nivolumab and Nivolumab + Relatlimab Fixed-dose Combinations

Melanoma

Spain, United States, Italy, Chile, Greece, Argentina
Baptist Health South Florida
Bristol-Myers Squibb; NovoCure Ltd.

Terminated

Trial of Combination TTF(Optune), Nivolumab Plus/Minus Ipilimumab for Recurrent Glioblastoma

Recurrent Glioblastoma

United States
HUYABIO International, LLC.
Bristol-Myers Squibb

Recruiting

Study Comparing Investigational Drug HBI-8000 Combined With Nivolumab vs. Nivolumab in Patients With Advanced Melanoma

Unresectable or Metastatic Melanoma | Progressive Brain Metastasis

Spain, United States, Italy, Japan, Belgium, France, New Zealand, Brazil, Korea, Republic of, Australia, Germany, Singapore, Czechia, Austria, South Africa, United Kingdom, Puerto Rico
Michael B. Atkins, MD
Bristol-Myers Squibb; Hoosier Cancer Research Network

Active, not recruiting

Study of Front Line Therapy With Nivolumab and Salvage Nivolumab + Ipilimumab in Patients With Advanced Renal Cell Carcinoma

Advanced Renal Cell Carcinoma

United States
Jason J. Luke, MD
Array BioPharma

Active, not recruiting

Study of ARRY-614 Plus Either Nivolumab or Nivolumab+Ipilimumab

Melanoma | Renal Cell Carcinoma | Solid Tumor | Non-small Cell Lung Cancer | Head and Neck Squamous Cell Carcinoma

United States
Bristol-Myers Squibb

Completed

An Investigational Immuno-therapy Study for Safety of Nivolumab in Combination With Ipilimumab to Treat Advanced Cancers

Lung Cancer

Italy, United States, France, Russian Federation, Spain, Argentina, Belgium, Brazil, Canada, Chile, Czechia, Germany, Greece, Hungary, Mexico, Netherlands, Poland, Romania, Switzerland, Turkey, United Kingdom
National Health Research Institutes, Taiwan
National Taiwan University Hospital; Mackay Memorial Hospital; China Medical... and other collaborators

Recruiting

Nivolumab Plus Ipilimumab as Neoadjuvant Therapy for Hepatocellular Carcinoma (HCC)

Hepatocellular Carcinoma (HCC)

Taiwan
IRCCS San Raffaele
Bristol-Myers Squibb

Recruiting

An Open Label, Single-arm, Phase 2 Study of Neoadjuvant Nivolumab and Nab-paclitaxel Before Radical Cystectomy for Patients With Muscle-invasive Bladder Cancer (NURE-Combo) (NURE-Combo)

Muscle-Invasive Bladder Carcinoma

Italy

Brentuximab Vedotin and Nivolumab With or Without Ipilimumab in Treating Patients With Relapsed or Refractory Hodgkin Lymphoma

A Phase I Study With an Expansion Cohort/Randomized Phase II Study of the Combinations of Ipilimumab, Nivolumab and Brentuximab Vedotin in Patients With Relapsed/Refractory Hodgkin Lymphoma

Study Overview

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Clinical Trials on Recurrent Classic Hodgkin Lymphoma

Clinical Trials on Nivolumab

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