Testing The Addition of a New Anti-cancer Drug, Venetoclax, to the Usual Treatment (Ibrutinib and Obinutuzumab) in Untreated, Older Patients With Chronic Lymphocytic Leukemia
Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma
About this trial
This is an interventional treatment trial for Chronic Lymphocytic Leukemia
Eligibility Criteria
Inclusion Criteria:
- PRE-REGISTRATION ELIGIBILITY CRITERIA (STEP 0)
- Patients must have been diagnosed with chronic lymphocytic leukemia (CLL) (> 5000 B-cells per uL of peripheral blood at any point during the course of their disease) or small lymphocytic lymphoma (SLL) with < 5000 B-cells per uL of blood but with disease-associated lymphadenopathy
- This blood submission is mandatory prior to registration/randomization to perform fluorescence in situ hybridization (FISH) centrally that will be used for stratification. It should be obtained as soon after pre-registration as possible
- REGISTRATION ELIGIBILITY CRITERIA (STEP 1)
Patients must be diagnosed with CLL or SLL in accordance with 2018 International Workshop on Chronic Lymphocytic Leukemia (IWCLL) criteria that includes all of the following:
- >= 5 x10^9 B lymphocytes (5000/uL) in the peripheral blood measured by flow cytometry at any point in the course of the disease or less peripheral blood involvement but disease-associated lymphadenopathy
- On local morphologic review, the leukemic cells must be small mature lymphocytes, and prolymphocytes must not exceed 55% of the blood lymphocytes
- Neoplastic cells on immunophenotype (performed locally) must reveal a clonal B-cell population, which express the B cell surface markers of CD19 and CD20, as well as the T-cell antigen CD5. Patients with bright surface immunoglobulin expression or lack of CD23 expression in >10% of cells must lack t(11;14) translocation by interphase cytogenetics
Patients must be intermediate or high-risk Rai stage CLL or SLL
- Intermediate risk (formerly stage I/II) is defined by lymphadenopathy and/or hepatomegaly or splenomegaly without anemia or thrombocytopenia
- High risk (formerly stage III/IV) is defined by splenomegaly and/or anemia (hemoglobin < 11g/dL) not attributable to autoimmune hemolytic anemia and/or thrombocytopenia (platelets [plt] < 100 x10^9/L) not attributable to autoimmune thrombocytopenia
Patients must meet criteria for treatment as defined by 2018 IWCLL guidelines which includes at least one of the following criteria:
- Evidence of marrow failure as manifested by the development or worsening of anemia or thrombocytopenia (not attributable to autoimmune hemolytic anemia or thrombocytopenia)
- Massive (>= 6 cm below the costal margin), progressive or symptomatic splenomegaly
- Massive nodes (>= 10 cm) or progressive or symptomatic lymphadenopathy
- Progressive lymphocytosis with a lymphocyte doubling time < 6 months or an increase of >= 50% over a 2 month period
- Autoimmune anemia and/or thrombocytopenia that is poorly responsive to standard therapy
- Symptomatic or functional extranodal involvement (e.g. skin, kidney, lung, spine)
Constitutional symptoms, which include any of the following:
- Unintentional weight loss of 10% or more within 6 months
- Significant fatigue
- Fevers > 100.5 degrees Fahrenheit (F) for 2 weeks or more without evidence of infection
- Night sweats >= 1 month without evidence of infection
- Treatment with rituximab and/or high dose corticosteroids for autoimmune complications of CLL/SLL must be complete at least 4 weeks prior to enrollment. Palliative steroids must be at a dose not higher than 20 mg/day of prednisone or equivalent corticosteroid at the time of registration
- Age >= 65 years
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- Absolute neutrophil count (ANC) >= 1,000/mm^3 except if due to bone marrow involvement
- Platelet count (untransfused) >= 30,000/mm^3 except if due to bone marrow involvement
- Calculated (Calc.) creatinine clearance >= 40 mL/min (by Cockcroft-Gault)
- Bilirubin =< 1.5 x upper limit of normal (ULN) except if due to liver involvement, hemolysis, or Gilbert's disease
- Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 2.5 x upper limit of normal (ULN) except if due to liver involvement
- If evidence of chronic hepatitis B virus (HBV) infection, HBV viral load must be undetectable on suppressive therapy if indicated
- Please note: Intravenous immunoglobulin therapy (IVIG) can cause a false positive hepatitis B serology. If patients receiving routine IVIG have core antibody or surface antigen positivity without evidence of active viremia (negative hepatitis B deoxyribonucleic acid [DNA]) they may still participate in the study, must have hepatitis serologies and hepatitis B DNA monitored periodically by the treating physician
- If history of hepatitis C virus (HCV) infection, must be treated with undetectable HCV viral load
- Human immunodeficiency virus (HIV)-infected patients on effective antiretroviral therapy with undetectable viral load within 6 months are eligible for this trial
- Central fluorescent in situ hybridization (FISH) blood results are mandatory prior to registration/randomization for it will be used for stratification
- Patients must be able to swallow capsules and not have the following conditions: disease significantly affecting gastrointestinal absorption, resection of the stomach or small bowel, partial or complete bowel obstruction
- Patients must be able to receive either a xanthine oxidase inhibitor or rasburicase for prophylaxis/treatment of tumor lysis syndrome (TLS)
- RE-REGISTRATION ELIGIBILITY CRITERIA (STEP 2)
- Completion of treatment through cycle 14 day 28, and remain on ibrutinib therapy
- Receipt of central BM MRD results
- Response assessment completed with CR determination
Exclusion Criteria:
- Patients must not have had prior therapy for CLL/SLL (except palliative steroids or treatment of autoimmune complications of CLL with rituximab or steroids)
- Patients must not have any history of Richter's transformation or prolymphocytic leukemia (prolymphocytes in blood > 55%)
- Patients with class III or class IV heart failure by New York Heart Association, those with unstable angina, and those with uncontrolled arrhythmia are not eligible
- Patients who have had a myocardial infarction, intracranial bleed, or stroke within the past 6 months are not eligible
- Patients must not be receiving active systemic anticoagulation with heparin or warfarin. Patients on warfarin must discontinue the drug for at least 10 days prior to registration on the study
- Chronic concomitant treatment with strong inhibitors of CYP3A4/5 is not allowed on this study. Patients on strong CYP3A inhibitors must discontinue the drug for 14 days prior to registration on the study
- Chronic concomitant treatment with strong CYP3A4/5 inducers is not allowed. Patients must discontinue the drug 14 days prior to registration on the study
- Patients must not require more than 20 mg prednisone or equivalent corticosteroid daily
- Patients must not have uncontrolled active systemic infection requiring intravenous antibiotics
- Patients must not have a known allergy to mannitol
- Patients must not have prior significant hypersensitivity to rituximab (not including infusion reactions)
- Patients may not have had major surgery within 10 days prior to registration, or minor surgery within 7 days prior to registration. Examples of minor surgery include dental surgery, insertion of a venous access device, skin biopsy, or aspiration for a joint. The decision about whether a surgery is major or minor can be made at the discretion of the treating physician
Sites / Locations
- University of Alabama at Birmingham Cancer Center
- Anchorage Associates in Radiation Medicine
- Anchorage Radiation Therapy Center
- Alaska Breast Care and Surgery LLC
- Alaska Oncology and Hematology LLC
- Alaska Women's Cancer Care
- Anchorage Oncology Centre
- Katmai Oncology Group
- Providence Alaska Medical Center
- Fairbanks Memorial Hospital
- Kingman Regional Medical Center
- Cancer Center at Saint Joseph's
- Mayo Clinic Hospital in Arizona
- Mayo Clinic in Arizona
- University of Arizona Cancer Center-Orange Grove Campus
- Banner University Medical Center - Tucson
- University of Arizona Cancer Center-North Campus
- Mercy Hospital Fort Smith
- CHI Saint Vincent Cancer Center Hot Springs
- John L McClellan Memorial Veterans Hospital
- Kaiser Permanente-Anaheim
- Mission Hope Medical Oncology - Arroyo Grande
- PCR Oncology
- Kaiser Permanente-Baldwin Park
- Kaiser Permanente-Bellflower
- Providence Saint Joseph Medical Center/Disney Family Cancer Center
- Community Cancer Institute
- University Oncology Associates
- UC Irvine Health Cancer Center-Newport
- City of Hope Comprehensive Cancer Center
- Kaiser Permanente-Fontana
- Kaiser Permanente - Harbor City
- Kaiser Permanente-Irvine
- Tibor Rubin VA Medical Center
- Kaiser Permanente Los Angeles Medical Center
- Kaiser Permanente West Los Angeles
- Kaiser Permanente-Ontario
- UC Irvine Health/Chao Family Comprehensive Cancer Center
- Desert Regional Medical Center
- Stanford Cancer Institute Palo Alto
- Kaiser Permanente - Panorama City
- Kaiser Permanente-Riverside
- Kaiser Permanente-San Diego Mission
- Kaiser Permanente-San Diego Zion
- Pacific Central Coast Health Center-San Luis Obispo
- Kaiser Permanente-San Marcos
- Mission Hope Medical Oncology - Santa Maria
- Kaiser Permanente-Woodland Hills
- Rocky Mountain Cancer Centers-Aurora
- The Medical Center of Aurora
- Rocky Mountain Regional VA Medical Center
- Boulder Community Hospital
- Boulder Community Foothills Hospital
- Rocky Mountain Cancer Centers-Boulder
- Rocky Mountain Cancer Centers - Centennial
- Penrose-Saint Francis Healthcare
- Rocky Mountain Cancer Centers-Penrose
- Cancer Center of Colorado at Sloan's Lake
- Denver Health Medical Center
- Kaiser Permanente-Franklin
- National Jewish Health-Main Campus
- The Women's Imaging Center
- Porter Adventist Hospital
- Colorado Blood Cancer Institute
- Presbyterian - Saint Lukes Medical Center - Health One
- Rocky Mountain Cancer Centers-Midtown
- SCL Health Saint Joseph Hospital
- Rocky Mountain Cancer Centers-Rose
- Rose Medical Center
- Western Surgical Care
- Mercy Medical Center
- Southwest Oncology PC
- Mountain Blue Cancer Care Center - Swedish
- Rocky Mountain Cancer Centers - Swedish
- Swedish Medical Center
- The Melanoma and Skin Cancer Institute
- Mountain Blue Cancer Care Center
- National Jewish Health-Western Hematology Oncology
- Saint Mary's Hospital and Regional Medical Center
- Grand Valley Oncology
- North Colorado Medical Center
- Good Samaritan Medical Center
- Kaiser Permanente-Rock Creek
- Rocky Mountain Cancer Centers-Lakewood
- Saint Anthony Hospital
- Rocky Mountain Cancer Centers-Littleton
- Littleton Adventist Hospital
- Kaiser Permanente-Lone Tree
- Rocky Mountain Cancer Centers-Sky Ridge
- Sky Ridge Medical Center
- Longmont United Hospital
- Rocky Mountain Cancer Centers-Longmont
- McKee Medical Center
- Parker Adventist Hospital
- Rocky Mountain Cancer Centers-Parker
- Saint Mary Corwin Medical Center
- Rocky Mountain Cancer Centers - Pueblo
- National Jewish Health-Northern Hematology Oncology
- Rocky Mountain Cancer Centers-Thornton
- SCL Health Lutheran Medical Center
- Smilow Cancer Hospital-Derby Care Center
- Smilow Cancer Hospital Care Center-Fairfield
- Smilow Cancer Hospital Care Center at Glastonbury
- Smilow Cancer Hospital Care Center - Guiford
- Smilow Cancer Hospital Care Center at Saint Francis
- Smilow Cancer Center/Yale-New Haven Hospital
- Yale University
- Yale-New Haven Hospital North Haven Medical Center
- Smilow Cancer Hospital-Orange Care Center
- Smilow Cancer Hospital Care Center-Trumbull
- Smilow Cancer Hospital-Waterbury Care Center
- Smilow Cancer Hospital Care Center - Waterford
- Veterans Affairs Connecticut Healthcare System-West Haven Campus
- Beebe South Coastal Health Campus
- Beebe Medical Center
- Delaware Clinical and Laboratory Physicians PA
- Helen F Graham Cancer Center
- Medical Oncology Hematology Consultants PA
- Christiana Care Health System-Christiana Hospital
- Beebe Health Campus
- TidalHealth Nanticoke / Allen Cancer Center
- Christiana Care Health System-Wilmington Hospital
- UM Sylvester Comprehensive Cancer Center at Coral Gables
- Broward Health North
- UM Sylvester Comprehensive Cancer Center at Deerfield Beach
- Holy Cross Hospital
- Broward Health Medical Center
- UM Sylvester Comprehensive Cancer Center at Hollywood
- University of Miami Miller School of Medicine-Sylvester Cancer Center
- UM Sylvester Comprehensive Cancer Center at Plantation
- Cleveland Clinic-Weston
- University Cancer and Blood Center LLC
- Augusta Oncology Associates PC-D'Antignac
- Augusta Oncology Associates PC-Wheeler
- Augusta University Medical Center
- Atlanta VA Medical Center
- Lewis Cancer and Research Pavilion at Saint Joseph's/Candler
- Hawaii Cancer Care - Savio
- Pali Momi Medical Center
- Queen's Cancer Center - Pearlridge
- The Cancer Center of Hawaii-Pali Momi
- Island Urology-Hilo
- Hawaii Cancer Care Inc - Waterfront Plaza
- Island Urology
- Queen's Cancer Cenrer - POB I
- Queen's Medical Center
- Straub Clinic and Hospital
- University of Hawaii Cancer Center
- Hawaii Cancer Care Inc-Liliha
- Kuakini Medical Center
- Queen's Cancer Center - Kuakini
- The Cancer Center of Hawaii-Liliha
- Kapiolani Medical Center for Women and Children
- Wilcox Memorial Hospital and Kauai Medical Clinic
- Saint Alphonsus Cancer Care Center-Boise
- Saint Luke's Cancer Institute - Boise
- Saint Alphonsus Cancer Care Center-Caldwell
- Kootenai Health - Coeur d'Alene
- Walter Knox Memorial Hospital
- Saint Luke's Cancer Institute - Fruitland
- Idaho Urologic Institute-Meridian
- Saint Luke's Cancer Institute - Meridian
- Saint Alphonsus Medical Center-Nampa
- Saint Luke's Cancer Institute - Nampa
- Kootenai Clinic Cancer Services - Post Falls
- Kootenai Cancer Clinic
- Saint Luke's Cancer Institute - Twin Falls
- Saint Anthony's Health
- Rush - Copley Medical Center
- Illinois CancerCare-Bloomington
- Loyola Center for Health at Burr Ridge
- Illinois CancerCare-Canton
- Memorial Hospital of Carbondale
- SIH Cancer Institute
- Illinois CancerCare-Carthage
- Centralia Oncology Clinic
- Northwestern University
- Rush University Medical Center
- University of Illinois
- University of Chicago Comprehensive Cancer Center
- Carle on Vermilion
- Cancer Care Specialists of Illinois - Decatur
- Decatur Memorial Hospital
- Northwestern Medicine Cancer Center Kishwaukee
- Illinois CancerCare-Dixon
- Carle Physician Group-Effingham
- Crossroads Cancer Center
- Illinois CancerCare-Eureka
- NorthShore University HealthSystem-Evanston Hospital
- Illinois CancerCare-Galesburg
- Western Illinois Cancer Treatment Center
- Northwestern Medicine Cancer Center Delnor
- NorthShore University HealthSystem-Glenbrook Hospital
- Ingalls Memorial Hospital
- NorthShore University HealthSystem-Highland Park Hospital
- Loyola Medicine Homer Glen
- Illinois CancerCare-Kewanee Clinic
- Northwestern Medicine Lake Forest Hospital
- Illinois CancerCare-Macomb
- Carle Physician Group-Mattoon/Charleston
- Loyola University Medical Center
- Marjorie Weinberg Cancer Center at Loyola-Gottlieb
- Good Samaritan Regional Health Center
- UC Comprehensive Cancer Center at Silver Cross
- Cancer Care Center of O'Fallon
- University of Chicago Medicine-Orland Park
- Illinois CancerCare-Ottawa Clinic
- Illinois CancerCare-Pekin
- OSF Saint Francis Radiation Oncology at Pekin Cancer Treatment Center
- Illinois CancerCare-Peoria
- OSF Saint Francis Radiation Oncology at Peoria Cancer Center
- Methodist Medical Center of Illinois
- OSF Saint Francis Medical Center
- Illinois CancerCare-Peru
- Valley Radiation Oncology
- Illinois CancerCare-Princeton
- SwedishAmerican Regional Cancer Center/ACT
- North Shore Medical Center
- Southern Illinois University School of Medicine
- Springfield Clinic
- Memorial Medical Center
- Southwest Illinois Health Services LLP
- Carle Cancer Center
- The Carle Foundation Hospital
- Northwestern Medicine Cancer Center Warrenville
- Illinois CancerCare - Washington
- Rush-Copley Healthcare Center
- Franciscan Health Indianapolis
- Franciscan Health Mooresville
- Reid Health
- Mary Greeley Medical Center
- McFarland Clinic PC - Ames
- University of Iowa Healthcare Cancer Services Quad Cities
- McFarland Clinic PC-Boone
- Physicians' Clinic of Iowa PC
- Medical Oncology and Hematology Associates-West Des Moines
- Mercy Cancer Center-West Lakes
- Alegent Health Mercy Hospital
- Greater Regional Medical Center
- Medical Oncology and Hematology Associates-Laurel
- Mercy Medical Center - Des Moines
- McFarland Clinic PC-Trinity Cancer Center
- University of Iowa/Holden Comprehensive Cancer Center
- McFarland Clinic PC-Jefferson
- McFarland Clinic PC-Marshalltown
- Siouxland Regional Cancer Center
- MercyOne Waterloo Medical Center
- Mercy Medical Center-West Lakes
- Coffeyville Regional Medical Center
- Central Care Cancer Center - Garden City
- Central Care Cancer Center - Great Bend
- HaysMed University of Kansas Health System
- Cancer Center of Kansas-Independence
- University of Kansas Cancer Center-West
- University of Kansas Cancer Center
- Lawrence Memorial Hospital
- Kansas Institute of Medicine Cancer and Blood Center
- Minimally Invasive Surgery Hospital
- Olathe Health Cancer Center
- Menorah Medical Center
- University of Kansas Cancer Center-Overland Park
- Ascension Via Christi - Pittsburg
- Salina Regional Health Center
- University of Kansas Health System Saint Francis Campus
- University of Kansas Hospital-Westwood Cancer Center
- Cancer Center of Kansas-Wichita Medical Arts Tower
- Ascension Via Christi Hospitals Wichita
- Cancer Center of Kansas - Wichita
- Wesley Medical Center
- Flaget Memorial Hospital
- Commonwealth Cancer Center-Corbin
- Saint Joseph Radiation Oncology Resource Center
- Saint Joseph Hospital East
- Saint Joseph London
- Jewish Hospital
- Saints Mary and Elizabeth Hospital
- UofL Health Medical Center Northeast
- Jewish Hospital Medical Center South
- Christus Saint Frances Cabrini Hospital
- Ochsner Medical Center Jefferson
- Eastern Maine Medical Center
- Lafayette Family Cancer Center-EMMC
- University of Maryland/Greenebaum Cancer Center
- Saint Agnes Hospital
- Western Maryland Regional Medical Center
- Tufts Medical Center
- Lahey Hospital and Medical Center
- Lowell General Hospital
- Mercy Medical Center
- Baystate Medical Center
- Saint Joseph Mercy Hospital
- Bronson Battle Creek
- Saint Joseph Mercy Brighton
- Trinity Health IHA Medical Group Hematology Oncology - Brighton
- Henry Ford Cancer Institute-Downriver
- Saint Joseph Mercy Canton
- Trinity Health IHA Medical Group Hematology Oncology - Canton
- Caro Cancer Center
- Saint Joseph Mercy Chelsea
- Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital
- Hematology Oncology Consultants-Clarkston
- Newland Medical Associates-Clarkston
- Henry Ford Macomb Hospital-Clinton Township
- Beaumont Hospital - Dearborn
- Henry Ford Medical Center-Fairlane
- Wayne State University/Karmanos Cancer Institute
- Henry Ford Hospital
- Ascension Saint John Hospital
- Great Lakes Cancer Management Specialists-Doctors Park
- Green Bay Oncology - Escanaba
- Weisberg Cancer Treatment Center
- Beaumont Hospital - Farmington Hills
- Genesee Cancer and Blood Disease Treatment Center
- Genesee Hematology Oncology PC
- Genesys Hurley Cancer Institute
- Hurley Medical Center
- Helen DeVos Children's Hospital at Spectrum Health
- Mercy Health Saint Mary's
- Spectrum Health at Butterworth Campus
- Academic Hematology Oncology Specialists
- Great Lakes Cancer Management Specialists-Van Elslander Cancer Center
- Michigan Breast Specialists-Grosse Pointe Woods
- William Beaumont Hospital-Grosse Pointe
- Allegiance Health
- Bronson Methodist Hospital
- West Michigan Cancer Center
- Ascension Borgess Cancer Center
- Borgess Medical Center
- Sparrow Hospital
- Hope Cancer Clinic
- Trinity Health Saint Mary Mercy Livonia Hospital
- Great Lakes Cancer Management Specialists-Macomb Medical Campus
- Michigan Breast Specialists-Macomb Township
- Saint Mary's Oncology/Hematology Associates of Marlette
- Mercy Health Mercy Campus
- Lakeland Hospital Niles
- Cancer and Hematology Centers of Western Michigan - Norton Shores
- Henry Ford Medical Center-Columbus
- 21st Century Oncology-Pontiac
- Hope Cancer Center
- Newland Medical Associates-Pontiac
- Saint Joseph Mercy Oakland
- Spectrum Health Reed City Hospital
- Great Lakes Cancer Management Specialists-Rochester Hills
- Michigan Cancer Specialists
- Oakland Colon Rectal Associates
- Cancer Care Associates PC
- Comprehensive Medical Center PLLC
- Hematology Oncology Consultants PC
- Oakland Medical Group
- William Beaumont Hospital-Royal Oak
- Ascension Saint Mary's Hospital
- Oncology Hematology Associates of Saginaw Valley PC
- Lakeland Medical Center Saint Joseph
- Marie Yeager Cancer Center
- Henry Ford Macomb Health Center - Shelby Township
- Bhadresh Nayak MD PC-Sterling Heights
- Premier Hematology Oncology Care
- Ascension Saint Joseph Hospital
- Munson Medical Center
- Michigan Institute of Urology-Town Center
- William Beaumont Hospital - Troy
- Hematology Oncology Consultants PC-Troy
- Advanced Breast Care Center PLLC
- Great Lakes Cancer Management Specialists-Macomb Professional Building
- Macomb Hematology Oncology PC
- Michigan Breast Specialists-Warren
- Saint John Macomb-Oakland Hospital
- Henry Ford West Bloomfield Hospital
- Saint Mary's Oncology/Hematology Associates of West Branch
- Metro Health Hospital
- Huron Gastroenterology PC
- Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus
- Riverwood Healthcare Center
- Sanford Joe Lueken Cancer Center
- Essentia Health Saint Joseph's Medical Center
- Fairview Ridges Hospital
- Minnesota Oncology - Burnsville
- Cambridge Medical Center
- Mercy Hospital
- Essentia Health - Deer River Clinic
- Essentia Health Saint Mary's - Detroit Lakes Clinic
- Essentia Health Cancer Center
- Essentia Health Saint Mary's Medical Center
- Miller-Dwan Hospital
- Fairview Southdale Hospital
- Lake Region Healthcare Corporation-Cancer Care
- Essentia Health - Fosston
- Unity Hospital
- Essentia Health Hibbing Clinic
- Mayo Clinic Health Systems-Mankato
- Fairview Clinics and Surgery Center Maple Grove
- Minnesota Oncology Hematology PA-Maplewood
- Saint John's Hospital - Healtheast
- Abbott-Northwestern Hospital
- Hennepin County Medical Center
- Minneapolis VA Medical Center
- Health Partners Inc
- Monticello Cancer Center
- New Ulm Medical Center
- Essentia Health - Park Rapids
- Fairview Northland Medical Center
- North Memorial Medical Health Center
- Mayo Clinic in Rochester
- Coborn Cancer Center at Saint Cloud Hospital
- Park Nicollet Clinic - Saint Louis Park
- Regions Hospital
- United Hospital
- Essentia Health Sandstone
- Saint Francis Regional Medical Center
- Lakeview Hospital
- Sanford Thief River Falls Medical Center
- Essentia Health Virginia Clinic
- Ridgeview Medical Center
- Rice Memorial Hospital
- Minnesota Oncology Hematology PA-Woodbury
- Sanford Cancer Center Worthington
- Fairview Lakes Medical Center
- Saint Louis Cancer and Breast Institute-Ballwin
- Central Care Cancer Center - Bolivar
- Parkland Health Center-Bonne Terre
- Cox Cancer Center Branson
- Saint Francis Medical Center
- Southeast Cancer Center
- Siteman Cancer Center at West County Hospital
- Parkland Health Center - Farmington
- Centerpoint Medical Center LLC
- Capital Region Southwest Campus
- Freeman Health System
- Mercy Hospital Joplin
- Truman Medical Centers
- Research Medical Center
- University of Kansas Cancer Center - North
- University of Kansas Cancer Center - Lee's Summit
- University of Kansas Cancer Center at North Kansas City Hospital
- Delbert Day Cancer Institute at PCRMC
- Mercy Clinic-Rolla-Cancer and Hematology
- Heartland Regional Medical Center
- Saint Louis Cancer and Breast Institute-South City
- Washington University School of Medicine
- Mercy Hospital South
- Siteman Cancer Center-South County
- Missouri Baptist Medical Center
- Siteman Cancer Center at Christian Hospital
- Mercy Hospital Saint Louis
- Siteman Cancer Center at Saint Peters Hospital
- Sainte Genevieve County Memorial Hospital
- Mercy Hospital Springfield
- CoxHealth South Hospital
- Missouri Baptist Sullivan Hospital
- Missouri Baptist Outpatient Center-Sunset Hills
- Mercy Hospital Washington
- Community Hospital of Anaconda
- Billings Clinic Cancer Center
- Saint Vincent Healthcare
- Saint Vincent Frontier Cancer Center
- Bozeman Deaconess Hospital
- Saint James Community Hospital and Cancer Treatment Center
- Benefis Healthcare- Sletten Cancer Institute
- Great Falls Clinic
- Saint Peter's Community Hospital
- Kalispell Regional Medical Center
- Saint Patrick Hospital - Community Hospital
- Community Medical Hospital
- Nebraska Medicine-Bellevue
- CHI Health Saint Francis
- Heartland Hematology and Oncology
- CHI Health Good Samaritan
- Saint Elizabeth Regional Medical Center
- Nebraska Methodist Hospital
- Nebraska Medicine-Village Pointe
- Alegent Health Immanuel Medical Center
- Hematology and Oncology Consultants PC
- Alegent Health Bergan Mercy Medical Center
- Alegent Health Lakeside Hospital
- Creighton University Medical Center
- University of Nebraska Medical Center
- Midlands Community Hospital
- Carson Tahoe Regional Medical Center
- Cancer and Blood Specialists-Henderson
- Comprehensive Cancer Centers of Nevada - Henderson
- Comprehensive Cancer Centers of Nevada-Horizon Ridge
- Las Vegas Cancer Center-Henderson
- OptumCare Cancer Care at Seven Hills
- Comprehensive Cancer Centers of Nevada-Southeast Henderson
- GenesisCare USA - Henderson
- Las Vegas Urology - Green Valley
- Las Vegas Urology - Pebble
- Urology Specialists of Nevada - Green Valley
- Las Vegas Urology - Pecos
- Desert West Surgery
- OptumCare Cancer Care at Charleston
- University Medical Center of Southern Nevada
- Hope Cancer Care of Nevada
- Radiation Oncology Centers of Nevada Central
- Urology Specialists of Nevada - Central
- GenesisCare USA - Las Vegas
- Sunrise Hospital and Medical Center
- Las Vegas Prostate Cancer Center
- Las Vegas Urology - Sunset
- Urology Specialists of Nevada - Southwest
- Radiation Oncology Centers of Nevada Southeast
- Ann M Wierman MD LTD
- Comprehensive Cancer Centers of Nevada - Northwest
- GenesisCare USA - Vegas Tenaya
- Las Vegas Urology - Cathedral Rock
- Las Vegas Urology - Smoke Ranch
- OptumCare Cancer Care at MountainView
- Urology Specialists of Nevada - Northwest
- Alliance for Childhood Diseases/Cure 4 the Kids Foundation
- Comprehensive Cancer Centers of Nevada - Town Center
- Comprehensive Cancer Centers of Nevada-Summerlin
- Summerlin Hospital Medical Center
- Las Vegas Cancer Center-Medical Center
- Comprehensive Cancer Centers of Nevada
- GenesisCare USA - Fort Apache
- OptumCare Cancer Care at Fort Apache
- Comprehensive Cancer Centers of Nevada - Central Valley
- University Cancer Center
- Hope Cancer Care of Nevada-Pahrump
- Renown Regional Medical Center
- Saint Mary's Regional Medical Center
- Radiation Oncology Associates
- New Hampshire Oncology Hematology PA-Concord
- Solinsky Center for Cancer Care
- Monmouth Medical Center Southern Campus
- Monmouth Medical Center
- Morristown Medical Center
- Rutgers Cancer Institute of New Jersey
- The Valley Hospital-Luckow Pavilion
- Neurosurgeons of New Jersey-Ridgewood
- Valley Hospital
- Overlook Hospital
- Valley Health System-Hematology/Oncology
- University of New Mexico Cancer Center
- Memorial Medical Center - Las Cruces
- Hematology Oncology Associates of Central New York-Auburn
- Roswell Park Cancer Institute
- Cancer Institute at Saint Francis Hospital
- Hematology Oncology Associates of Central New York-East Syracuse
- Glens Falls Hospital
- Northwell Health/Center for Advanced Medicine
- North Shore University Hospital
- Long Island Jewish Medical Center
- NYP/Weill Cornell Medical Center
- Upstate Cancer Center at Oneida
- University of Rochester
- State University of New York Upstate Medical University
- Hematology Oncology Associates of Central New York-Onondaga Hill
- Good Samaritan Hospital Medical Center
- Mission Hospital
- Messino Cancer Centers
- Waverly Hematology Oncology
- UNC Lineberger Comprehensive Cancer Center
- Wake Forest University at Clemmons
- Southeastern Medical Oncology Center-Clinton
- Duke University Medical Center
- Southeastern Medical Oncology Center-Goldsboro
- Wayne Memorial Hospital
- East Carolina University
- Margaret R Pardee Memorial Hospital
- Onslow Memorial Hospital
- Southeastern Medical Oncology Center-Jacksonville
- Vidant Oncology-Kenansville
- Novant Health Cancer Institute - Kernersville
- Vidant Oncology-Kinston
- Novant Health Cancer Institute - Mount Airy
- FirstHealth of the Carolinas-Moore Regional Hospital
- Vidant Oncology-Richlands
- Novant Health Cancer Institute - Statesville
- Novant Health Cancer Institute - Thomasville
- Novant Health Cancer Institute - Wilkesboro
- Wake Forest Baptist Health - Wilkes Medical Center
- Novant Health Forsyth Medical Center
- Novant Health Oncology Specialists
- Wake Forest University Health Sciences
- Sanford Bismarck Medical Center
- Essentia Health Cancer Center-South University Clinic
- Sanford South University Medical Center
- Sanford Medical Center Fargo
- Sanford Broadway Medical Center
- Sanford Roger Maris Cancer Center
- Essentia Health - Jamestown Clinic
- Indu and Raj Soin Medical Center
- Strecker Cancer Center-Belpre
- Saint Elizabeth Boardman Hospital
- Dayton Physicians LLC-Miami Valley South
- Miami Valley Hospital South
- Geauga Hospital
- Adena Regional Medical Center
- Good Samaritan Hospital - Cincinnati
- Oncology Hematology Care Inc-Kenwood
- Bethesda North Hospital
- TriHealth Cancer Institute-Westside
- TriHealth Cancer Institute-Anderson
- Case Western Reserve University
- Cleveland Clinic Cancer Center/Fairview Hospital
- Cleveland Clinic Foundation
- Ohio State University Comprehensive Cancer Center
- Mount Carmel East Hospital
- Columbus Oncology and Hematology Associates Inc
- Riverside Methodist Hospital
- Grant Medical Center
- The Mark H Zangmeister Center
- Mount Carmel Health Center West
- Doctors Hospital
- Good Samaritan Hospital - Dayton
- Miami Valley Hospital
- Dayton Physician LLC-Miami Valley Hospital North
- Miami Valley Hospital North
- Dayton Veterans Affairs Medical Center
- Delaware Health Center-Grady Cancer Center
- Grady Memorial Hospital
- Dublin Methodist Hospital
- Armes Family Cancer Center
- Blanchard Valley Hospital
- Orion Cancer Care
- Atrium Medical Center-Middletown Regional Hospital
- Dayton Physicians LLC-Atrium
- Central Ohio Breast and Endocrine Surgery
- Dayton Physicians LLC-Wayne
- Wayne Hospital
- Mount Carmel Grove City Hospital
- Greater Dayton Cancer Center
- First Dayton Cancer Care
- Kettering Medical Center
- Fairfield Medical Center
- Saint Rita's Medical Center
- OhioHealth Mansfield Hospital
- Cleveland Clinic Cancer Center Mansfield
- Marietta Memorial Hospital
- OhioHealth Marion General Hospital
- Hillcrest Hospital Cancer Center
- UH Seidman Cancer Center at Lake Health Mentor Campus
- UH Seidman Cancer Center at Southwest General Hospital
- Knox Community Hospital
- Licking Memorial Hospital
- Newark Radiation Oncology
- University Hospitals Parma Medical Center
- Mercy Health Perrysburg Cancer Center
- Southern Ohio Medical Center
- University Hospitals Portage Medical Center
- North Coast Cancer Care
- UH Seidman Cancer Center at Firelands Regional Medical Center
- Springfield Regional Cancer Center
- Springfield Regional Medical Center
- Cleveland Clinic Cancer Center Strongsville
- Saint Vincent Mercy Medical Center
- Mercy Health - Saint Anne Hospital
- Dayton Physicians LLC-Upper Valley
- Upper Valley Medical Center
- University Hospitals Sharon Health Center
- South Pointe Hospital
- Saint Joseph Warren Hospital
- Saint Ann's Hospital
- UH Seidman Cancer Center at Saint John Medical Center
- Cleveland Clinic Wooster Family Health and Surgery Center
- Wright-Patterson Medical Center
- Saint Elizabeth Youngstown Hospital
- Genesis Healthcare System Cancer Care Center
- Cancer Centers of Southwest Oklahoma Research
- University of Oklahoma Health Sciences Center
- Mercy Hospital Oklahoma City
- Oklahoma Cancer Specialists and Research Institute-Tulsa
- Saint Alphonsus Medical Center-Baker City
- Saint Charles Health System
- Clackamas Radiation Oncology Center
- Providence Cancer Institute Clackamas Clinic
- Bay Area Hospital
- Providence Newberg Medical Center
- Saint Alphonsus Medical Center-Ontario
- Providence Portland Medical Center
- Providence Saint Vincent Medical Center
- Oregon Health and Science University
- Saint Charles Health System-Redmond
- Lehigh Valley Hospital-Cedar Crest
- Lehigh Valley Hospital - Muhlenberg
- Christiana Care Health System-Concord Health Center
- Chambersburg Hospital
- Geisinger Medical Center
- Pocono Medical Center
- Ephrata Cancer Center
- Ephrata Community Hospital
- Adams Cancer Center
- Cherry Tree Cancer Center
- Geisinger Medical Center-Cancer Center Hazleton
- Lehigh Valley Hospital-Hazleton
- Sechler Family Cancer Center
- Geisinger Medical Oncology-Lewisburg
- Lewistown Hospital
- Geisinger Cancer Services-Pottsville
- Community Medical Center
- Geisinger Medical Oncology-Selinsgrove
- Geisinger Medical Group
- Geisinger Wyoming Valley/Henry Cancer Center
- WellSpan Health-York Cancer Center
- WellSpan Health-York Hospital
- Smilow Cancer Hospital Care Center - Westerly
- Saint Joseph's/Candler - Bluffton Campus
- Prisma Health Cancer Institute - Spartanburg
- Medical University of South Carolina
- Prisma Health Cancer Institute - Laurens
- Prisma Health Cancer Institute - Easley
- Gibbs Cancer Center-Gaffney
- Saint Francis Hospital
- BI-LO Charities Children's Cancer Center
- Prisma Health Cancer Institute - Butternut
- Prisma Health Cancer Institute - Faris
- Prisma Health Greenville Memorial Hospital
- Saint Francis Cancer Center
- Prisma Health Cancer Institute - Eastside
- Prisma Health Cancer Institute - Greer
- Gibbs Cancer Center-Pelham
- South Carolina Cancer Specialists PC
- Prisma Health Cancer Institute - Seneca
- Spartanburg Medical Center
- MGC Hematology Oncology-Union
- Avera Cancer Institute-Aberdeen
- Avera Cancer Institute at Pierre
- Sanford Cancer Center Oncology Clinic
- Avera Cancer Institute
- Sanford USD Medical Center - Sioux Falls
- Memorial Hospital
- Cookeville Regional Medical Center
- Pulmonary Medicine Center of Chattanooga-Hixson
- Memorial GYN Plus
- The Don and Sybil Harrington Cancer Center
- Saint Joseph Regional Cancer Center
- UT Southwestern/Simmons Cancer Center-Dallas
- STCC at DHR Health Institute for Research and Development
- UT Southwestern/Simmons Cancer Center-Fort Worth
- UT Southwestern Clinical Center at Richardson/Plano
- American Fork Hospital / Huntsman Intermountain Cancer Center
- Sandra L Maxwell Cancer Center
- Logan Regional Hospital
- Intermountain Medical Center
- McKay-Dee Hospital Center
- Utah Valley Regional Medical Center
- Riverton Hospital
- Saint George Regional Medical Center
- Utah Cancer Specialists-Salt Lake City
- Huntsman Cancer Institute/University of Utah
- LDS Hospital
- University of Virginia Cancer Center
- Centra Lynchburg Hematology-Oncology Clinic Inc
- Virginia Cancer Institute
- Virginia Commonwealth University/Massey Cancer Center
- VCU Community Memorial Health Center
- Providence Regional Cancer System-Aberdeen
- MultiCare Auburn Medical Center
- Virginia Mason Bainbridge Island Medical Center
- Overlake Medical Center
- PeaceHealth Saint Joseph Medical Center
- Harrison HealthPartners Hematology and Oncology-Bremerton
- Harrison Medical Center
- Highline Medical Center-Main Campus
- Providence Regional Cancer System-Centralia
- Swedish Cancer Institute-Edmonds
- Saint Elizabeth Hospital
- Providence Regional Cancer Partnership
- Virginia Mason Federal Way Medical Center
- Saint Francis Hospital
- Tacoma/Valley Radiation Oncology Centers-Gig Harbor
- MultiCare Gig Harbor Medical Park
- Swedish Cancer Institute-Issaquah
- Kadlec Clinic Hematology and Oncology
- Northwest Cancer Clinic
- Providence Regional Cancer System-Lacey
- Saint Clare Hospital
- PeaceHealth Saint John Medical Center
- Virginia Mason Lynnwood Medical Center
- Jefferson Healthcare
- Harrison HealthPartners Hematology and Oncology-Poulsbo
- MultiCare Good Samaritan Hospital
- Tacoma/Valley Radiation Oncology Centers-Puyallup
- Valley Medical Center
- Virginia Mason Medical Center
- Pacific Gynecology Specialists
- Swedish Medical Center-Ballard Campus
- Kaiser Permanente Washington
- Swedish Medical Center-First Hill
- Swedish Medical Center-Cherry Hill
- PeaceHealth United General Medical Center
- Providence Regional Cancer System-Shelton
- MultiCare Deaconess Cancer and Blood Specialty Center - Valley
- MultiCare Deaconess Cancer and Blood Specialty Center - Downtown
- MultiCare Deaconess Cancer and Blood Specialty Center - North
- Tacoma/Valley Radiation Oncology Centers-Jackson Hall
- Franciscan Research Center-Northwest Medical Plaza
- Mary Bridge Children's Hospital and Health Center
- MultiCare Tacoma General Hospital
- Northwest Medical Specialties PLLC
- Tacoma/Valley Radiation Oncology Centers-Saint Joe's
- PeaceHealth Southwest Medical Center
- Providence Saint Mary Regional Cancer Center
- North Star Lodge Cancer Center at Yakima Valley Memorial Hospital
- Providence Regional Cancer System-Yelm
- Langlade Hospital and Cancer Center
- ThedaCare Regional Cancer Center
- Ascension Saint Elizabeth Hospital
- Duluth Clinic Ashland
- Northwest Wisconsin Cancer Center
- Ascension Southeast Wisconsin Hospital - Elmbrook Campus
- Aurora Cancer Care-Southern Lakes VLCC
- Ascension Calumet Hospital
- HSHS Sacred Heart Hospital
- Marshfield Medical Center-EC Cancer Center
- Mayo Clinic Health System-Eau Claire Clinic
- Aurora Health Center-Fond du Lac
- Ascension Saint Francis - Reiman Cancer Center
- Ascension Southeast Wisconsin Hospital - Franklin
- Aurora Health Care Germantown Health Center
- Aurora Cancer Care-Grafton
- Saint Vincent Hospital Cancer Center Green Bay
- Saint Vincent Hospital Cancer Center at Saint Mary's
- Aurora BayCare Medical Center
- Aurora Cancer Care-Kenosha South
- Gundersen Lutheran Medical Center
- Mayo Clinic Health System-Franciscan Healthcare
- William S Middleton VA Medical Center
- Dean Hematology and Oncology Clinic
- University of Wisconsin Carbone Cancer Center
- Holy Family Memorial Hospital
- Aurora Bay Area Medical Group-Marinette
- Saint Vincent Hospital Cancer Center at Marinette
- Marshfield Medical Center-Marshfield
- Aspirus Medford Hospital
- Ascension Columbia Saint Mary's Hospital Ozaukee
- Aurora Cancer Care-Milwaukee
- Ascension Southeast Wisconsin Hospital - Saint Joseph Campus
- Ascension Columbia Saint Mary's Hospital - Milwaukee
- Ascension Saint Francis Hospital
- Aurora Saint Luke's Medical Center
- Medical College of Wisconsin
- Aurora Sinai Medical Center
- Marshfield Clinic-Minocqua Center
- ProHealth D N Greenwald Center
- Froedtert and MCW Moorland Reserve Health Center
- Cancer Center of Western Wisconsin
- ProHealth Oconomowoc Memorial Hospital
- Saint Vincent Hospital Cancer Center at Oconto Falls
- Ascension Mercy Hospital
- Vince Lombardi Cancer Clinic - Oshkosh
- Ascension All Saints Hospital
- Aurora Cancer Care-Racine
- Ascension Saint Mary's Hospital
- Marshfield Medical Center-Rice Lake
- HSHS Saint Nicholas Hospital
- Vince Lombardi Cancer Clinic-Sheboygan
- Ascension Saint Michael's Hospital
- Marshfield Medical Center-River Region at Stevens Point
- Saint Vincent Hospital Cancer Center at Sturgeon Bay
- Aurora Medical Center in Summit
- Vince Lombardi Cancer Clinic-Two Rivers
- ProHealth Waukesha Memorial Hospital
- UW Cancer Center at ProHealth Care
- ThedaCare Cancer Care - Waupaca
- Aspirus Regional Cancer Center
- Ascension Medical Group Southeast Wisconsin - Mayfair Road
- Aurora Cancer Care-Milwaukee West
- Aurora West Allis Medical Center
- Marshfield Medical Center - Weston
- Aspirus Cancer Care - Wisconsin Rapids
- Marshfield Clinic - Wisconsin Rapids Center
- Cheyenne Regional Medical Center-West
- Billings Clinic-Cody
- Welch Cancer Center
Arms of the Study
Arm 1
Arm 2
Active Comparator
Experimental
Arm I (ibrutinib, obinutuzumab)
Arm II (ibrutinib, obinutuzumab, venetoclax)
Patients receive ibrutinib PO QD on days 1-28. Patients also receive obinutuzumab IV on days 1, 2, 8, and 15 of cycle 1, and on day 1 of cycles 2-6. Treatment repeats every 28 days for up to 14 cycles in the absence of disease progression or unacceptable toxicity. Beginning cycle 15, patients receive ibrutinib PO QD every 28 days in the absence of disease progression or unacceptable toxicity.
Patients receive ibrutinib PO QD on days 1-28. Patients also receive obinutuzumab IV on days 1, 2, 8, and 15 of cycle 1, and on day 1 of cycles 2-6. Beginning cycle 3, patients also receive venetoclax PO QD on days 1-28. Treatment repeats every 28 days for 14 cycles in the absence of disease progression or unacceptable toxicity. All patients will then receive a 15th cycle of ibrutinib. Beginning cycle 16, patients who do not achieve a BM MRD negative CR, receive ibrutinib PO QD every 28 days in the absence of disease progression or unacceptable toxicity. Patients who achieve a BM MRD negative CR undergo observation every 3 cycles for 6 years, then every 6 cycles thereafter.