Recurrent Classic Hodgkin LymphomaPhase 1/2NCT01896999
Brentuximab Vedotin and Nivolumab With or Without Ipilimumab in Treating Patients With Relapsed or Refractory Hodgkin Lymphoma
A Phase 1/2 study testing Biopsy Procedure, Biospecimen Collection and Brentuximab Vedotin in people with Recurrent Classic Hodgkin Lymphoma and Refractory Classic Hodgkin Lymphoma, run by National Cancer Institute (NCI) at 479 sites in United States.
Trial summary
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). Read more about this study
- Who is it for?
- Ages 12 years and older
- Conditions the study is for
- Recurrent Classic Hodgkin Lymphoma, Refractory Classic Hodgkin Lymphoma
- What is being tested?
- Biopsy Procedure, Biospecimen Collection and Brentuximab Vedotin
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 146 participants
- Where
- 479 sitesUnited States
- Study dates
- 7 Mar 2014to 30 Jun 2027
- Phase
- Phase 1/2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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)
Show all 82Show fewer
- 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 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 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/sex 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
Who cannot join
None listed.
Trial locations and contacts
479 sites in 1 country.
300 sites in 1 country
United States300 sites
Providence Regional Cancer System-Aberdeen
Aberdeen, Washington, 98520
Riverwood Healthcare Center
Aitkin, Minnesota, 56431
Children's Hospital Medical Center of Akron
Akron, Ohio, 44308
Albany Medical Center
Albany, New York, 12208
University of New Mexico Cancer Center
Albuquerque, New Mexico, 87106
OSF Saint Anthony's Health Center
Alton, Illinois, 62002
American Fork Hospital / Huntsman Intermountain Cancer Center
American Fork, Utah, 84003
Community Hospital of Anaconda
Anaconda, Montana, 59711
Anchorage Associates in Radiation Medicine
Anchorage, Alaska, 98508
Anchorage Radiation Therapy Center
Anchorage, Alaska, 99504
Alaska Breast Care and Surgery LLC
Anchorage, Alaska, 99508
Alaska Oncology and Hematology LLC
Anchorage, Alaska, 99508
Alaska Women's Cancer Care
Anchorage, Alaska, 99508
Anchorage Oncology Centre
Anchorage, Alaska, 99508
Katmai Oncology Group
Anchorage, Alaska, 99508
Providence Alaska Medical Center
Anchorage, Alaska, 99508
Kaiser Permanente-Deer Valley Medical Center
Antioch, California, 94531
Mission Hope Medical Oncology - Arroyo Grande
Arroyo Grande, California, 93420
PCR Oncology
Arroyo Grande, California, 93420
Duluth Clinic Ashland
Ashland, Wisconsin, 54806
Northwest Wisconsin Cancer Center
Ashland, Wisconsin, 54806
Emory University Hospital/Winship Cancer Institute
Atlanta, Georgia, 30322
Children's Healthcare of Atlanta - Arthur M Blank Hospital
Atlanta, Georgia, 30329
MultiCare Auburn Medical Center
Auburn, Washington, 98001
Rocky Mountain Cancer Centers-Aurora
Aurora, Colorado, 80012
The Medical Center of Aurora
Aurora, Colorado, 80012
Rush-Copley Medical Center
Aurora, Illinois, 60504
Dell Children's Medical Center of Central Texas
Austin, Texas, 78723
Saint Alphonsus Cancer Care Center-Baker City
Baker City, Oregon, 97814
Mercy Oncology and Hematology - Clayton-Clarkson
Ballwin, Missouri, 63011
Saint Agnes Hospital
Baltimore, Maryland, 21229
Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore, Maryland, 21287
CommonSpirit Saint Joseph Hospital - Bardstown
Bardstown, Kentucky, 40004
LSU Health Baton Rouge-North Clinic
Baton Rouge, Louisiana, 70805
Our Lady of the Lake Physician Group
Baton Rouge, Louisiana, 70808
Our Lady of The Lake
Baton Rouge, Louisiana, 70808
Louisiana Hematology Oncology Associates LLC
Baton Rouge, Louisiana, 70809
Mary Bird Perkins Cancer Center
Baton Rouge, Louisiana, 70809
Overlake Medical Center
Bellevue, Washington, 98004
PeaceHealth Saint Joseph Medical Center
Bellingham, Washington, 98225
Saint Charles Health System
Bend, Oregon, 97701
Walter Reed National Military Medical Center
Bethesda, Maryland, 20889-5600
Billings Clinic Cancer Center
Billings, Montana, 59101
Saint Vincent Healthcare
Billings, Montana, 59101
Saint Vincent Frontier Cancer Center
Billings, Montana, 59102
Children's Hospital of Alabama
Birmingham, Alabama, 35233
University of Alabama at Birmingham Cancer Center
Birmingham, Alabama, 35233
Illinois CancerCare-Bloomington
Bloomington, Illinois, 61704
Prisma Health Cancer Institute - Spartanburg
Boiling Springs, South Carolina, 29316
Saint Alphonsus Cancer Care Center-Boise
Boise, Idaho, 83706
Saint Luke's Cancer Institute - Boise
Boise, Idaho, 83712
Central Care Cancer Center - Bolivar
Bolivar, Missouri, 65613
Parkland Health Center-Bonne Terre
Bonne Terre, Missouri, 63628
Tufts Medical Center
Boston, Massachusetts, 02111
Boulder Community Foothills Hospital
Boulder, Colorado, 80303
Rocky Mountain Cancer Centers-Boulder
Boulder, Colorado, 80304
Bozeman Health Deaconess Hospital
Bozeman, Montana, 59715
Essentia Health Saint Joseph's Medical Center
Brainerd, Minnesota, 56401
Cox Cancer Center Branson
Branson, Missouri, 65616
United Hospital Center
Bridgeport, West Virginia, 26330
Saint Joseph Regional Cancer Center
Bryan, Texas, 77802
Roswell Park Cancer Institute
Buffalo, New York, 14263
Providence Saint Joseph Medical Center/Disney Family Cancer Center
Burbank, California, 91505
Saint Anne Hospital
Burien, Washington, 98166
Aurora Cancer Care-Southern Lakes VLCC
Burlington, Wisconsin, 53105
Saint James Community Hospital and Cancer Treatment Center
Butte, Montana, 59701
Saint Alphonsus Cancer Care Center-Caldwell
Caldwell, Idaho, 83605
Illinois CancerCare-Canton
Canton, Illinois, 61520
Mercy Cancer Center - Cape Girardeau
Cape Girardeau, Missouri, 63703
Saint Francis Medical Center
Cape Girardeau, Missouri, 63703
Memorial Hospital of Carbondale
Carbondale, Illinois, 62902
Carson Tahoe Regional Medical Center
Carson City, Nevada, 89703
SIH Cancer Institute
Carterville, Illinois, 62918
Illinois CancerCare-Carthage
Carthage, Illinois, 62321
Sandra L Maxwell Cancer Center
Cedar City, Utah, 84720
Rocky Mountain Cancer Centers - Centennial
Centennial, Colorado, 80112
Centralia Oncology Clinic
Centralia, Illinois, 62801
Providence Regional Cancer System-Centralia
Centralia, Washington, 98531
UNC Lineberger Comprehensive Cancer Center
Chapel Hill, North Carolina, 27599
Carolinas Medical Center/Levine Cancer Institute
Charlotte, North Carolina, 28203
Memorial Hospital
Chattanooga, Tennessee, 37404
Saint Luke's Hospital
Chesterfield, Missouri, 63017
Cheyenne Regional Medical Center-West
Cheyenne, Wyoming, 82001
Northwestern University
Chicago, Illinois, 60611
Rush MD Anderson Cancer Center
Chicago, Illinois, 60612
University of Illinois
Chicago, Illinois, 60612
Marshfield Clinic-Chippewa Center
Chippewa Falls, Wisconsin, 54729
Good Samaritan Hospital - Cincinnati
Cincinnati, Ohio, 45220
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229
Bethesda North Hospital
Cincinnati, Ohio, 45242
TriHealth Cancer Institute-Westside
Cincinnati, Ohio, 45247
TriHealth Cancer Institute-Anderson
Cincinnati, Ohio, 45255
Siteman Cancer Center at Saint Peters Hospital
City of Saint Peters, Missouri, 63376
Clackamas Radiation Oncology Center
Clackamas, Oregon, 97015
Providence Cancer Institute Clackamas Clinic
Clackamas, Oregon, 97015
MetroHealth Medical Center
Cleveland, Ohio, 44109
Southeastern Medical Oncology Center-Clinton
Clinton, North Carolina, 28328
Mercy Cancer Center-West Lakes
Clive, Iowa, 50325
UI Health Care Mission Cancer and Blood - West Des Moines Clinic
Clive, Iowa, 50325
Billings Clinic-Cody
Cody, Wyoming, 82414
Kootenai Health - Coeur d'Alene
Coeur d'Alene, Idaho, 83814
Penrose-Saint Francis Healthcare
Colorado Springs, Colorado, 80907
Rocky Mountain Cancer Centers-Penrose
Colorado Springs, Colorado, 80907
Prisma Health Richland Hospital
Columbia, South Carolina, 29203
Nationwide Children's Hospital
Columbus, Ohio, 43205
Bay Area Hospital
Coos Bay, Oregon, 97420
Commonwealth Cancer Center-Corbin
Corbin, Kentucky, 40701
Driscoll Children's Hospital
Corpus Christi, Texas, 78411
Alegent Health Mercy Hospital
Council Bluffs, Iowa, 51503
Northshore Oncology Associates-Covington
Covington, Louisiana, 70433
Greater Regional Medical Center
Creston, Iowa, 50801
Siteman Cancer Center at West County Hospital
Creve Coeur, Missouri, 63141
Carle at The Riverfront
Danville, Illinois, 61832
Cancer Care Specialists of Illinois - Decatur
Decatur, Illinois, 62526
Decatur Memorial Hospital
Decatur, Illinois, 62526
Essentia Health - Deer River Clinic
Deer River, Minnesota, 56636
Cancer Center of Colorado at Sloan's Lake
Denver, Colorado, 80204
Denver Health Medical Center
Denver, Colorado, 80204
National Jewish Health-Main Campus
Denver, Colorado, 80206
The Women's Imaging Center
Denver, Colorado, 80209
AdventHealth Porter
Denver, Colorado, 80210
Colorado Blood Cancer Institute
Denver, Colorado, 80218
Presbyterian - Saint Lukes Medical Center - Health One
Denver, Colorado, 80218
Rocky Mountain Cancer Centers-Midtown
Denver, Colorado, 80218
Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center
Denver, Colorado, 80218
Saint Joseph Hospital - Cancer Centers of Colorado
Denver, Colorado, 80218
Rocky Mountain Cancer Centers-Rose
Denver, Colorado, 80220
Rose Medical Center
Denver, Colorado, 80220
Western Surgical Care
Denver, Colorado, 80220
Mercy Medical Center - Des Moines
Des Moines, Iowa, 50314
UI Health Care Mission Cancer and Blood - Laurel Clinic
Des Moines, Iowa, 50314
Essentia Health Saint Mary's - Detroit Lakes Clinic
Detroit Lakes, Minnesota, 56501
Illinois CancerCare-Dixon
Dixon, Illinois, 61021
Kaiser Permanente Dublin
Dublin, California, 94568
Essentia Health Cancer Center
Duluth, Minnesota, 55805
Essentia Health Saint Mary's Medical Center
Duluth, Minnesota, 55805
Miller-Dwan Hospital
Duluth, Minnesota, 55805
CommonSpirit Cancer Center Mercy
Durango, Colorado, 81301
Mercy Medical Center
Durango, Colorado, 81301
Prisma Health Cancer Institute - Easley
Easley, South Carolina, 29640
Marshfield Medical Center-EC Cancer Center
Eau Claire, Wisconsin, 54701
Swedish Cancer Institute-Edmonds
Edmonds, Washington, 98026
Carle Physician Group-Effingham
Effingham, Illinois, 62401
Crossroads Cancer Center
Effingham, Illinois, 62401
El Paso Children's Hospital
El Paso, Texas, 79905
Walter Knox Memorial Hospital
Emmett, Idaho, 83617
Mountain Blue Cancer Care Center - Swedish
Englewood, Colorado, 80113
Rocky Mountain Cancer Centers - Swedish
Englewood, Colorado, 80113
Swedish Medical Center
Englewood, Colorado, 80113
Saint Elizabeth Hospital
Enumclaw, Washington, 98022
Illinois CancerCare-Eureka
Eureka, Illinois, 61530
Deaconess Clinic Downtown
Evansville, Indiana, 47713
Providence Regional Cancer Partnership
Everett, Washington, 98201
Fairbanks Memorial Hospital
Fairbanks, Alaska, 99701
Essentia Health Cancer Center-South University Clinic
Fargo, North Dakota, 58103
Parkland Health Center - Farmington
Farmington, Missouri, 63640
Saint Francis Hospital
Federal Way, Washington, 98003
Lake Region Healthcare Corporation-Cancer Care
Fergus Falls, Minnesota, 56537
Aurora Health Center-Fond du Lac
Fond du Lac, Wisconsin, 54937
Regional Cancer Center-Lee Memorial Health System
Fort Myers, Florida, 33905
Golisano Children's Hospital of Southwest Florida
Fort Myers, Florida, 33908
Mercy Hospital Fort Smith
Fort Smith, Arkansas, 72903
Cook Children's Medical Center
Fort Worth, Texas, 76104
Essentia Health - Fosston
Fosston, Minnesota, 56542
Kaiser Permanente-Fremont
Fremont, California, 94538
Fresno Cancer Center
Fresno, California, 93720
Kaiser Permanente-Fresno
Fresno, California, 93720
Saint Luke's Cancer Institute - Fruitland
Fruitland, Idaho, 83619
Illinois CancerCare-Galesburg
Galesburg, Illinois, 61401
Western Illinois Cancer Treatment Center
Galesburg, Illinois, 61401
Central Care Cancer Center - Garden City
Garden City, Kansas, 67846
Aurora Health Care Germantown Health Center
Germantown, Wisconsin, 53022
MultiCare Gig Harbor Medical Park
Gig Harbor, Washington, 98335
Mountain Blue Cancer Care Center
Golden, Colorado, 80401
National Jewish Health-Western Hematology Oncology
Golden, Colorado, 80401
Southeastern Medical Oncology Center-Goldsboro
Goldsboro, North Carolina, 27534
Wayne Memorial Hospital
Goldsboro, North Carolina, 27534
Aurora Cancer Care-Grafton
Grafton, Wisconsin, 53024
Nebraska Cancer Specialists/Oncology Hematology West PC
Grand Island, Nebraska, 68803
Saint Mary's Hospital and Regional Medical Center
Grand Junction, Colorado, 81501
Central Care Cancer Center - Great Bend
Great Bend, Kansas, 67530
Benefis Sletten Cancer Institute
Great Falls, Montana, 59405
Great Falls Clinic
Great Falls, Montana, 59405
Banner North Colorado Medical Center
Greeley, Colorado, 80631
Aurora BayCare Medical Center
Green Bay, Wisconsin, 54311
Saint Francis Hospital
Greenville, South Carolina, 29601
BI-LO Charities Children's Cancer Center
Greenville, South Carolina, 29605
Prisma Health Cancer Institute - Butternut
Greenville, South Carolina, 29605
Prisma Health Cancer Institute - Faris
Greenville, South Carolina, 29605
Prisma Health Greenville Memorial Hospital
Greenville, South Carolina, 29605
Saint Francis Cancer Center
Greenville, South Carolina, 29607
Prisma Health Cancer Institute - Eastside
Greenville, South Carolina, 29615
Prisma Health Cancer Institute - Greer
Greer, South Carolina, 29650
Hackensack University Medical Center
Hackensack, New Jersey, 07601
Saint Peter's Community Hospital
Helena, Montana, 59601
Cancer and Blood Specialists-Henderson
Henderson, Nevada, 89052
Comprehensive Cancer Centers of Nevada - Henderson
Henderson, Nevada, 89052
Comprehensive Cancer Centers of Nevada-Horizon Ridge
Henderson, Nevada, 89052
Las Vegas Cancer Center-Henderson
Henderson, Nevada, 89052
Comprehensive Cancer Centers of Nevada-Southeast Henderson
Henderson, Nevada, 89074
Las Vegas Urology - Green Valley
Henderson, Nevada, 89074
Las Vegas Urology - Pebble
Henderson, Nevada, 89074
Oncology Las Vegas - Henderson
Henderson, Nevada, 89074
Urology Specialists of Nevada - Green Valley
Henderson, Nevada, 89074
Penn State Milton S Hershey Medical Center
Hershey, Pennsylvania, 17033-0850
Essentia Health Hibbing Clinic
Hibbing, Minnesota, 55746
Pulmonary Medicine Center of Chattanooga-Hixson
Hixson, Tennessee, 37343
Kaiser Permanente Moanalua Medical Center
Honolulu, Hawaii, 96819
CHI Saint Vincent Cancer Center Hot Springs
Hot Springs, Arkansas, 71913
Oncology Center of The South Incorporated
Houma, Louisiana, 70360
Terrebonne General Medical Center
Houma, Louisiana, 70360
Indiana University/Melvin and Bren Simon Cancer Center
Indianapolis, Indiana, 46202
Swedish Cancer Institute-Issaquah
Issaquah, Washington, 98029
Onslow Memorial Hospital
Jacksonville, North Carolina, 28546
Southeastern Medical Oncology Center-Jacksonville
Jacksonville, North Carolina, 28546
Essentia Health - Jamestown Clinic
Jamestown, North Dakota, 58401
MU Health Care Goldschmidt Cancer Center
Jefferson City, Missouri, 65109
Duly Health and Care Joliet
Joliet, Illinois, 60435
Freeman Health System
Joplin, Missouri, 64804
Mercy Hospital Joplin
Joplin, Missouri, 64804
Logan Health Medical Center
Kalispell, Montana, 59901
Children's Mercy Hospitals and Clinics
Kansas City, Missouri, 64108
Fred and Pamela Buffett Cancer Center - Kearney
Kearney, Nebraska, 68845
CHI Health Good Samaritan
Kearney, Nebraska, 68847
Kadlec Clinic Hematology and Oncology
Kennewick, Washington, 99336
Aurora Cancer Care-Kenosha South
Kenosha, Wisconsin, 53142
Illinois CancerCare-Kewanee Clinic
Kewanee, Illinois, 61443
Kingman Regional Medical Center
Kingman, Arizona, 86401
East Tennessee Childrens Hospital
Knoxville, Tennessee, 37916
Gundersen Lutheran Medical Center
La Crosse, Wisconsin, 54601
Providence Regional Cancer System-Lacey
Lacey, Washington, 98503
Marshfield Medical Center - Ladysmith
Ladysmith, Wisconsin, 54848
Good Samaritan Hospital - Cancer Centers of Colorado
Lafayette, Colorado, 80026
CommonSpirit Saint Anthony Hospital Cancer Center
Lakewood, Colorado, 80228
Rocky Mountain Cancer Centers-Lakewood
Lakewood, Colorado, 80228
Monmouth Medical Center Southern Campus
Lakewood, New Jersey, 08701
Saint Clare Hospital
Lakewood, Washington, 98499
Las Vegas Urology - Pecos
Las Vegas, Nevada, 89074
Desert West Surgery
Las Vegas, Nevada, 89102
OptumCare Cancer Care at Charleston
Las Vegas, Nevada, 89102
University Medical Center of Southern Nevada
Las Vegas, Nevada, 89102
Hope Cancer Care of Nevada
Las Vegas, Nevada, 89103
Cancer and Blood Specialists-Shadow
Las Vegas, Nevada, 89106
Radiation Oncology Centers of Nevada Central
Las Vegas, Nevada, 89106
Urology Specialists of Nevada - Central
Las Vegas, Nevada, 89106
HealthCare Partners Medical Group Oncology/Hematology-Maryland Parkway
Las Vegas, Nevada, 89109
Sunrise Hospital and Medical Center
Las Vegas, Nevada, 89109
HealthCare Partners Medical Group Oncology/Hematology-San Martin
Las Vegas, Nevada, 89113
Las Vegas Prostate Cancer Center
Las Vegas, Nevada, 89113
Las Vegas Urology - Sunset
Las Vegas, Nevada, 89113
Urology Specialists of Nevada - Southwest
Las Vegas, Nevada, 89113
Radiation Oncology Centers of Nevada Southeast
Las Vegas, Nevada, 89119
Ann M Wierman MD LTD
Las Vegas, Nevada, 89128
Cancer and Blood Specialists-Tenaya
Las Vegas, Nevada, 89128
Comprehensive Cancer Centers of Nevada - Northwest
Las Vegas, Nevada, 89128
HealthCare Partners Medical Group Oncology/Hematology-Tenaya
Las Vegas, Nevada, 89128
Las Vegas Urology - Cathedral Rock
Las Vegas, Nevada, 89128
Las Vegas Urology - Smoke Ranch
Las Vegas, Nevada, 89128
Oncology Las Vegas - Tenaya
Las Vegas, Nevada, 89128
OptumCare Cancer Care at MountainView
Las Vegas, Nevada, 89128
Urology Specialists of Nevada - Northwest
Las Vegas, Nevada, 89128
Alliance for Childhood Diseases/Cure 4 the Kids Foundation
Las Vegas, Nevada, 89135
Comprehensive Cancer Centers of Nevada - Town Center
Las Vegas, Nevada, 89144
Comprehensive Cancer Centers of Nevada-Summerlin
Las Vegas, Nevada, 89144
Summerlin Hospital Medical Center
Las Vegas, Nevada, 89144
Las Vegas Cancer Center-Medical Center
Las Vegas, Nevada, 89148-2405
Comprehensive Cancer Centers of Nevada
Las Vegas, Nevada, 89148
HealthCare Partners Medical Group Oncology/Hematology-Centennial Hills
Las Vegas, Nevada, 89149
Comprehensive Cancer Centers of Nevada - Central Valley
Las Vegas, Nevada, 89169
University Cancer Center
Las Vegas, Nevada, 89169
OptumCare Cancer Care at Fort Apache
Las Vegas, Nevada, 89183
Cancer Centers of Southwest Oklahoma Research
Lawton, Oklahoma, 73505
Saint Joseph Radiation Oncology Resource Center
Lexington, Kentucky, 40504
CommonSpirit Saint Joseph Medical Center - East Lexington
Lexington, Kentucky, 40509
Saint Elizabeth Regional Medical Center
Lincoln, Nebraska, 68510
Rocky Mountain Cancer Centers-Littleton
Littleton, Colorado, 80120
AdventHealth Littleton
Littleton, Colorado, 80122
Logan Regional Hospital
Logan, Utah, 84321
CommonSpirit Saint Joseph Hospital London
London, Kentucky, 40741
Rocky Mountain Cancer Centers-Sky Ridge
Lone Tree, Colorado, 80124
Sky Ridge Medical Center
Lone Tree, Colorado, 80124
Monmouth Medical Center
Long Branch, New Jersey, 07740
Longmont United Hospital
Longmont, Colorado, 80501
Rocky Mountain Cancer Centers-Longmont
Longmont, Colorado, 80501
PeaceHealth Saint John Medical Center
Longview, Washington, 98632
Jewish Hospital
Louisville, Kentucky, 40202
Saints Mary and Elizabeth Hospital
Louisville, Kentucky, 40215
UofL Health Medical Center Northeast
Louisville, Kentucky, 40245
Banner North Colorado Medical Center - Loveland Campus
Loveland, Colorado, 80539
Illinois CancerCare-Macomb
Macomb, Illinois, 61455
University of Wisconsin Carbone Cancer Center - University Hospital
Madison, Wisconsin, 53792
Aurora Bay Area Medical Group-Marinette
Marinette, Wisconsin, 54143
Marshfield Medical Center-Marshfield
Marshfield, Wisconsin, 54449
WVUH-Berkely Medical Center
Martinsburg, West Virginia, 25401
Carle Physician Group-Mattoon/Charleston
Mattoon, Illinois, 61938
Saint Jude Children's Research Hospital
Memphis, Tennessee, 38105
Idaho Urologic Institute-Meridian
Meridian, Idaho, 83642
Saint Luke's Cancer Institute - Meridian
Meridian, Idaho, 83642
Aurora Cancer Care-Milwaukee
Milwaukee, Wisconsin, 53209
Aurora Saint Luke's Medical Center
Milwaukee, Wisconsin, 53215
About this study
Official title: 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.
Read the detailed description
PRIMARY OBJECTIVES:
- 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:
- 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:
- 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:
- 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:
- 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.
- Being tested
- Biopsy Procedure, Biospecimen Collection, Brentuximab Vedotin, Computed Tomography, Ipilimumab
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Biopsy ProcedureProcedure or surgery
Also called Biopsy, BIOPSY_TYPE, Bx
Undergo biopsy
Biospecimen CollectionProcedure or surgery
Also called Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen Collection
Undergo collection of blood
Brentuximab VedotinDrug
Also called ADC SGN-35, Adcetris, Anti-CD30 Antibody-Drug Conjugate SGN-35, Anti-CD30 Monoclonal Antibody-MMAE SGN-35
Given IV
Computed TomographyProcedure or surgery
Also called CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography
Undergo CT
IpilimumabBiological
Also called Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody, BMS 734016, BMS-734016, BMS734016
Given IV
NivolumabBiological
Also called ABP 206, BCD-263, BMS 936558, BMS-936558
Given IV
Positron Emission TomographyProcedure or surgery
Also called Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron emission tomography (procedure)
Undergo PET
| Study group | Role | What they receive |
|---|---|---|
| Phase I Arm I (brentuximab vedotin, ipilimumab) | Experimental | 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. Receives: Procedure: Biopsy Procedure; Procedure: Biospecimen Collection; Drug: Brentuximab Vedotin; Procedure: Computed Tomography; Biological: Ipilimumab; Procedure: Positron Emission Tomography |
| Phase I Arm II (brentuximab vedotin, nivolumab) | Experimental | 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. Receives: Procedure: Biopsy Procedure; Procedure: Biospecimen Collection; Drug: Brentuximab Vedotin; Procedure: Computed Tomography; Biological: Nivolumab; Procedure: Positron Emission Tomography |
| Phase I Arm III (brentuximab vedotin, nivolumab, ipilimumab) | Experimental | 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. Receives: Procedure: Biopsy Procedure; Procedure: Biospecimen Collection; Drug: Brentuximab Vedotin; Procedure: Computed Tomography; Biological: Ipilimumab; Biological: Nivolumab; Procedure: Positron Emission Tomography |
| Phase II Arm I (brentuximab vedotin, nivolumab) | Experimental | 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. Receives: Procedure: Biopsy Procedure; Procedure: Biospecimen Collection; Drug: Brentuximab Vedotin; Procedure: Computed Tomography; Biological: Nivolumab; Procedure: Positron Emission Tomography |
| Phase II Arm II (brentuximab vedotin, nivolumab, ipilimumab) | Experimental | 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. Receives: Procedure: Biopsy Procedure; Procedure: Biospecimen Collection; Drug: Brentuximab Vedotin; Procedure: Computed Tomography; Biological: Ipilimumab; Biological: Nivolumab; Procedure: Positron Emission Tomography |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum tolerated dose (MTD) of each combination (Phase I)
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.
Measured: 21 days
CR rate (Phase II)
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.
Measured: Up to 10 years
Secondary outcomes (10)
Complete response (CR) rate (Phase I)
Assessed using the Revised Response Criteria for Malignant Lymphoma and reported along with the 95% CI.
Measured: Up to 3 years
Partial response (PR) rate (Phase I)
Assessed using the Revised Response Criteria for Malignant Lymphoma and reported along with the 95% CI.
Measured: Up to 3 years
Overall response rate (ORR) rate (Phase I)
Assessed using the Revised Response Criteria for Malignant Lymphoma and reported along with the 95% CI.
Measured: Up to 3 years
Duration of response (DOR) (Phase I)
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.
Measured: From the documented beginning of response up to 3 years
Overall survival (OS) (Phase I)
OS will be estimated using Kaplan-Meier methodology. Greenwood's formula will be used to calculate 95% CI for the Kaplan-Meier estimates.
Measured: From the date of study entry up to 3 years
Progression-free survival (PFS) (Phase I)
PFS will be estimated using Kaplan-Meier methodology. Greenwood's formula will be used to calculate 95% CI for the Kaplan-Meier estimates.
Measured: From entry onto study up to 3 years
ORR (Phase II)
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.
Measured: Up to 10 years
PFS (or modified PFS) (Phase II)
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.
Measured: From randomization up to 10 years
OS (Phase II)
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.
Measured: From randomization up to 10 years
DOR (Phase II)
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.
Measured: From the documented beginning of response up to 10 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jul 2013 (estimated)
- Study start7 Mar 2014
- Primary completion30 Jun 2027 (estimated)
- Study completion30 Jun 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Recurrent Classic Hodgkin LymphomaStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 146 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Catherine S Diefenbach, Principal investigator, ECOG-ACRIN Cancer Research Group
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01896999
- Sponsor's protocol ID
- NCI-2013-01275
- Other IDs
- NCI-2013-01275, E4412, S14-00011, E4412, E4412, U10CA180820, U24CA196172
- Status last verified
- Sep 2026
- First submitted
- 8 Jul 2013
- Last updated
- 22 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
Publications
Diefenbach CS, Jegede O, Wang V, Ansell SM, Kostakoglu L, Steidl C, Natkunam Y, Scott DW, Ambinder RF, David KA, Advani RH, Bartlett NL, Robertson MJ, Thomas SP, Cohen J, Ibrahimi S, Goyal G, Mehta-Shah N, Amengual JE, Forlenza CJ, Cole PD, Duan F, Kelly K, Kahl BS. A randomized phase 2 study of ipilimumab, nivolumab, and brentuximab vedotin in patients with relapsed Hodgkin lymphoma. Blood. 2026 Apr 30;147(18):2041-2052. doi: 10.1182/blood.2025029546.
PubMed 41662628Gonzalez-Kozlova E, Huang HH, Jagede OA, Tuballes K, Del Valle DM, Kelly G, Patel M, Xie H, Harris J, Argueta K, Nie K, Barcessat V, Moravec R, Altreuter J, Duose DY, Kahl BS, Ansell SM, Yu J, Cerami E, Lindsay JR, Wistuba II, Kim-Schulze S, Diefenbach CS, Gnjatic S. Tumor-Immune Signatures of Treatment Resistance to Brentuximab Vedotin with Ipilimumab and/or Nivolumab in Hodgkin Lymphoma. Cancer Res Commun. 2024 Jul 1;4(7):1726-1737. doi: 10.1158/2767-9764.CRC-24-0252.
PubMed 38934093Mu-Mosley H, von Itzstein MS, Fattah F, Liu J, Zhu C, Xie Y, Wakeland EK, Park JY, Kahl BS, Diefenbach CS, Gerber DE. Distinct autoantibody profiles across checkpoint inhibitor types and toxicities. Oncoimmunology. 2024 May 9;13(1):2351255. doi: 10.1080/2162402X.2024.2351255. eCollection 2024.
PubMed 38737792Castellino SM, Giulino-Roth L, Harker-Murray P, Kahn JM, Forlenza C, Cho S, Hoppe B, Parsons SK, Kelly KM; COG Hodgkin Lymphoma Committee. Children's Oncology Group's 2023 blueprint for research: Hodgkin lymphoma. Pediatr Blood Cancer. 2023 Sep;70 Suppl 6(Suppl 6):e30580. doi: 10.1002/pbc.30580. Epub 2023 Jul 28.
PubMed 37505794Diefenbach 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.
PubMed 32853585