Assessing the Ability of Combination Treatment With Venetoclax to Permit Time Limited Therapy in 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:
Diagnosis of CLL according to the National Cancer Institute (NCI)/International Workshop on Chronic Lymphocytic Leukemia (IWCLL) criteria or small lymphocytic lymphoma (SLL) according to the World Health Organization (WHO) criteria. This includes previous documentation of:
- Biopsy-proven small lymphocytic lymphoma OR
Diagnosis of CLL according to the NCI/IWCLL criteria as evidenced by all of the following:
- Peripheral blood lymphocyte count of greater than 5 x10^9/L
Immunophenotype consistent with CLL defined as:
- The predominant population of lymphocytes share both B-cell antigens (CD19, CD20 [typically dim expression], or CD23) as well as CD5 in the absence of other pan-T-cell markers (CD3, CD2, etc).
- Clonality as evidenced by kappa or lambda light chain restriction (typically dim immunoglobulin expression)
- Negative fluorescent in situ hybridization (FISH) analysis for t(11;14)(IgH/CCND1) on peripheral blood or tissue biopsy (e.g. marrow aspirate) or negative immunohistochemical stains for cyclin D1 staining on involved tissue biopsy (e.g. marrow aspirate or lymph node biopsy)
- No prior chemotherapy, BTK inhibitor therapy, venetoclax, small molecule signaling inhibitor, or monoclonal anti-body therapy for treatment of CLL or SLL
Has met at least one of the following indications for treatment:
- Evidence of progressive marrow failure as manifested by the development of worsening anemia (hemoglobin [Hg] < 11 g/dl) and/or thrombocytopenia (platelets < 100 x 10^9/L)
- Symptomatic or progressive lymphadenopathy, splenomegaly, or hepatomegaly
One or more of the following disease-related symptoms:
- Weight loss >= 10% within the previous 6 months
- Grade 2 or 3 fatigue attributed to CLL
- Fevers > 100.5 degree Fahrenheit (F) for 2 weeks without evidence of infection
- Clinically significant night sweats without evidence of infection
- Progressive lymphocytosis (not due to the effects of corticosteroids) with an increase of > 50% over a two-month period or an anticipated doubling time of less than six months
- Eastern Cooperative Oncology Group (ECOG) performance status between 0-2
- Life expectancy of >= 12 months
- No deletion of 17p13 on cytogenetic analysis by FISH
- Glomerular filtration rate (GFR) > 40 mL/minute as calculated by the Cockcroft-Gault Formula (obtained =< 14 days prior to registration)
- Total bilirubin =< 1.5 x upper limit of normal (ULN) unless due to Gilbert's disease. For those with a total bilirubin > 1.5 x ULN, a direct bilirubin should be performed and must be < 1.5 mg/dL for Gilbert's to be diagnosed (obtained =< 14 days prior to registration)
Serum glutamic-oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST])/serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 3.0 x the institutional ULN (obtained =< 14 days prior to registration)
- NOTE: If value is higher due to hepatic involvement by CLL, patient is eligible
- Prothrombin time (PT)/international normalized ratio (INR) < 1.5 ULN and partial thromboplastin time (PTT) (activated partial thromboplastin time [aPTT]) < 1.5 x ULN (obtained =< 14 days prior to registration)
- No active hemolytic anemia requiring immunosuppressive therapy or other pharmacologic treatment. Patients who have a positive Coombs test but no evidence of hemolysis are NOT excluded from participation
- No current use of corticosteroids. EXCEPTION: Low doses of steroids (< 10 mg of prednisone or equivalent dose of other steroid; inhaled steroids) used for treatment of non-hematologic medical condition (e.g. chronic adrenal insufficiency) is permitted
- No previous autoimmune complications (e.g. autoimmune hemolytic anemia or immune thrombocytopenia) that have developed since the initial diagnosis of CLL and have required treatment with high dose corticosteroids (e.g. equivalent of > 20 mg/day of prednisone), monoclonal antibody based therapy, or chemotherapy. Prior use of corticosteroids for reasons other than treatment of autoimmune complications is allowed
No other active primary malignancy (other than non-melanomatous skin cancer or carcinoma in situ of the cervix) requiring treatment or limiting expected survival to =< 2 years
- NOTE: If there is a history of prior malignancy, the patient must not currently be receiving other specific treatment (other than hormonal therapy for their cancer)
- Able to adhere to the study visit schedule and other protocol requirements
- No major surgery within 4 weeks (28 days) of first dose of study drug or minor surgery within 3 days of first dose of study drug
- No radiation therapy =< 4 weeks prior to registration to Step 1
- Patients who are human immunodeficiency virus positive (HIV+) with undetectable HIV viral load are eligible provided they meet all other protocol criteria for participation and are not being treated with protease inhibitors or any non-nucleoside reverse transcriptase inhibitors (NNRTI) that are CYP3A4 inducers; if being treated for HIV, patients should be receiving an alternative antiretroviral therapy (ART) that is not a CYP3A inhibitor
Women of childbearing potential and sexually active males must be strongly advised to use accepted and highly effective method(s) of contraception or to abstain from sexual intercourse for the duration of their participation in the study and for:
- 18 months after the last dose of obinutuzumab
- 90 days after the last dose of ibrutinib, and
- 30 days after the last dose of venetoclax Male subjects must also agree to refrain from sperm donation until 90 days after the last dose of protocol treatment
Patient must be able to swallow capsules and not have the following conditions:
- Disease significantly affecting gastrointestinal function
- Resection of the stomach or small bowel
- Symptomatic inflammatory bowel disease
- Ulcerative colitis
- Partial or complete bowel obstruction
- Patient must undergo assessment with Timed Up and Go (TUG) test and comorbidity index
- Patient must be able to receive xanthine oxidase inhibitor or rasburicase for tumor lysis syndrome (TLS) prophylaxis
Exclusion Criteria:
Patients must not have any of the following conditions:
- Congestive heart failure or New York Heart Association Functional Classification III or IV congestive heart failure
- History of myocardial infarction, unstable angina, or acute coronary syndrome within 6 months prior to registration
- Recent infections requiring systemic treatment; need to have completed anti-biotic therapy > 14 days before the first dose of study drug
- Cerebral vascular accident or intracranial bleed within the last 6 months
- Infection with known chronic, active hepatitis C
- Positive serology for hepatitis B defined as a positive test for hepatitis B surface antigen (HBsAg); in addition, if negative for HBsAg but hepatitis B core antibody (HBcAb) positive (regardless of hepatitis B surface antibody [HBsAb] status), a hepatitis B deoxyribonucleic acid (DNA) test will be performed and, if positive the subject will be ineligible; if the hepatitis (Hep) B DNA test is negative (i.e. viral load undetectable) then the individual is eligible; if a patient who is HBsAg negative, HBsAb negative, HBcAb positive, and Hep B DNA negative is enrolled, they should be considered for either prophylactic anti-viral therapy (J Clin Oncol. 2013 Aug 1;31(22):2765-72) or careful monitoring for Hep B reactivation (J Clin Oncol. 2014 Nov 20;32(33):3736-43)
- Patients are not eligible if they require treatment with a strong cytochrome P450 (CYP) 3A inhibitor
Patients may not have received the following within 7 days prior to the first dose of study drug:
- Steroid therapy for anti-neoplastic intent
- Strong and moderate CYP3A inhibitors
- Strong and moderate CYP3A inducers
- Patients may not be on any other investigational agents
- Patients may not have received warfarin or another vitamin K antagonist in the preceding 30 days
- Women must not be pregnant or breast-feeding since this study involves investigational agents whose genotoxic, mutagenic, and teratogenic effects on the developing fetus and newborn are unknown; all females of childbearing potential must have a blood test within 2 weeks prior to registration to Step 1 to rule out pregnancy; a female of childbearing potential is defined as any woman, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy; or 3) 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)
- Patient must not be on any other systemic immunosuppressant therapy other than corticosteroids within 28 days of the first dose of study drug
- Patient must not be vaccinated with live, attenuated vaccines within 4 weeks of first dose of study drug
- Patient must not have any known bleeding disorders (e.g., von Willebrand's disease) or hemophilia
- Patient must not have currently active, clinically significant hepatic impairment (>= moderate hepatic impairment according to the NCI/Child Pugh classification)
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
- Kaiser Permanente-Anaheim
- Kaiser Permanente-Deer Valley Medical Center
- Mission Hope Medical Oncology - Arroyo Grande
- PCR Oncology
- Kaiser Permanente-Baldwin Park
- Kaiser Permanente-Bellflower
- Providence Saint Joseph Medical Center/Disney Family Cancer Center
- UC Irvine Health Cancer Center-Newport
- City of Hope Comprehensive Cancer Center
- Kaiser Permanente Dublin
- Kaiser Permanente-Fontana
- Kaiser Permanente-Fremont
- Fresno Cancer Center
- Kaiser Permanente-Fresno
- 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-Modesto
- Kaiser Permanente Oakland-Broadway
- Kaiser Permanente-Oakland
- Kaiser Permanente-Ontario
- UC Irvine Health/Chao Family Comprehensive Cancer Center
- Desert Regional Medical Center
- Stanford Cancer Institute Palo Alto
- VA Palo Alto Health Care System
- Kaiser Permanente - Panorama City
- Kaiser Permanente-Rancho Cordova Cancer Center
- Kaiser Permanente-Redwood City
- Kaiser Permanente-Richmond
- Kaiser Permanente-Riverside
- Rohnert Park Cancer Center
- Kaiser Permanente-Roseville
- The Permanente Medical Group-Roseville Radiation Oncology
- Kaiser Permanente Downtown Commons
- Kaiser Permanente-South Sacramento
- South Sacramento Cancer Center
- Kaiser Permanente - Sacramento
- Kaiser Permanente-San Diego Mission
- Kaiser Permanente-San Diego Zion
- Kaiser Permanente-San Francisco
- Kaiser Permanente-Santa Teresa-San Jose
- Kaiser Permanente San Leandro
- Pacific Central Coast Health Center-San Luis Obispo
- Kaiser Permanente-San Marcos
- Kaiser Permanente-San Rafael
- Kaiser San Rafael-Gallinas
- Kaiser Permanente Medical Center - Santa Clara
- Mission Hope Medical Oncology - Santa Maria
- Kaiser Permanente-Santa Rosa
- Kaiser Permanente Cancer Treatment Center
- Kaiser Permanente-South San Francisco
- Kaiser Permanente-Stockton
- Kaiser Permanente Medical Center-Vacaville
- Kaiser Permanente-Vallejo
- Kaiser Permanente-Walnut Creek
- 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
- Swedish Medical Center
- 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 - Guilford
- Smilow Cancer Hospital Care Center at Saint Francis
- 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
- Holy Cross Hospital
- Broward Health Medical Center
- Mayo Clinic in Florida
- University Cancer and Blood Center LLC
- Emory University Hospital Midtown
- Emory University Hospital/Winship Cancer Institute
- Emory Saint Joseph's Hospital
- Augusta University Medical Center
- Atlanta VA Medical Center
- Hawaii Cancer Care - Westridge
- 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
- Kaiser Permanente Moanalua Medical Center
- 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 Luke's Cancer Institute - Nampa
- Saint Alphonsus Cancer Care Center-Nampa
- Kootenai Clinic Cancer Services - Post Falls
- Kootenai Cancer Clinic
- Saint Luke's Cancer Institute - Twin Falls
- 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 Chicago Comprehensive Cancer Center
- Carle at The Riverfront
- 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
- Rush-Copley Healthcare Center
- Parkview Regional Medical Center
- Community Cancer Center East
- Community Cancer Center South
- Franciscan Health Indianapolis
- Community Cancer Center North
- Community Howard Regional Health
- Franciscan Health Mooresville
- Reid Health
- Union Hospital
- Mary Greeley Medical Center
- McFarland Clinic - Ames
- University of Iowa Healthcare Cancer Services Quad Cities
- McFarland Clinic - Boone
- Physicians' Clinic of Iowa PC
- Mercy Hospital
- Oncology Associates at Mercy Medical Center
- Medical Oncology and Hematology Associates-West Des Moines
- Mercy Cancer Center-West Lakes
- Alegent Health Mercy Hospital
- Greater Regional Medical Center
- Blank Children's Hospital
- Iowa Methodist Medical Center
- Medical Oncology and Hematology Associates-Des Moines
- Broadlawns Medical Center
- Mercy Medical Center - Des Moines
- Mission Cancer and Blood - Laurel
- Iowa Lutheran Hospital
- McFarland Clinic - Trinity Cancer Center
- Trinity Regional Medical Center
- University of Iowa/Holden Comprehensive Cancer Center
- McFarland Clinic - Jefferson
- McFarland Clinic - Marshalltown
- Siouxland Regional Cancer Center
- MercyOne Waterloo Cancer Center
- Methodist West Hospital
- 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
- Olathe Health Cancer 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
- Medical Center of Baton Rouge
- Ochsner High Grove
- Ochsner Medical Center Jefferson
- Harold Alfond Center for Cancer Care
- Waldo County General Hospital
- MaineHealth/SMHC Cancer Care and Blood Disorders-Biddeford
- Stephens Memorial Hospital
- Penobscot Bay Medical Center
- MaineHealth/SMHC Cancer Care and Blood Disorders-Sanford
- Maine Medical Partners - South Portland
- UPMC Western Maryland
- Tufts Medical Center
- Lahey Hospital and Medical Center
- Lowell General Hospital
- Mercy Medical Center
- Hickman Cancer Center
- Saint Joseph Mercy Hospital
- 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
- Academic Hematology Oncology Specialists
- Great Lakes Cancer Management Specialists-Van Elslander Cancer Center
- Michigan Breast Specialists-Grosse Pointe Woods
- Allegiance Health
- 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
- Toledo Clinic Cancer Centers-Monroe
- Henry Ford Medical Center-Columbus
- 21st Century Oncology-Pontiac
- Hope Cancer Center
- Newland Medical Associates-Pontiac
- Saint Joseph Mercy Oakland
- Huron Medical Center PC
- Lake Huron Medical Center
- Great Lakes Cancer Management Specialists-Rochester Hills
- 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
- Henry Ford Macomb Health Center - Shelby Township
- Bhadresh Nayak MD PC-Sterling Heights
- Premier Hematology Oncology Care
- Ascension Saint Joseph Hospital
- 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
- 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
- Hattiesburg Clinic - Hematology/Oncology Clinic
- Forrest General Hospital / Cancer 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
- Saint Luke's Hospital
- MU Health - University Hospital/Ellis Fischel Cancer Center
- Siteman Cancer Center at West County Hospital
- Parkland Health Center - Farmington
- Capital Region Southwest Campus
- Freeman Health System
- Mercy Hospital Joplin
- Truman Medical Centers
- The University of Kansas Cancer Center-South
- 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
- CHI Health Saint Francis
- Heartland Hematology and Oncology
- CHI Health Good Samaritan
- Saint Elizabeth Regional Medical Center
- Alegent Health Immanuel Medical Center
- Hematology and Oncology Consultants PC
- Alegent Health Bergan Mercy Medical Center
- Alegent Health Lakeside Hospital
- Creighton University 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
- Cancer and Blood Specialists-Shadow
- Radiation Oncology Centers of Nevada Central
- Urology Specialists of Nevada - Central
- GenesisCare USA - Las Vegas
- HealthCare Partners Medical Group Oncology/Hematology-Maryland Parkway
- Sunrise Hospital and Medical Center
- HealthCare Partners Medical Group Oncology/Hematology-San Martin
- 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
- Cancer and Blood Specialists-Tenaya
- Comprehensive Cancer Centers of Nevada - Northwest
- GenesisCare USA - Vegas Tenaya
- HealthCare Partners Medical Group Oncology/Hematology-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
- HealthCare Partners Medical Group Oncology/Hematology-Centennial Hills
- 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
- Elliot Hospital
- Solinsky Center for Cancer Care
- Ocean University Medical Center
- Monmouth Medical Center Southern Campus
- Monmouth Medical Center
- Southern Ocean County Medical Center
- Morristown Medical Center
- Jersey Shore Medical Center
- Rutgers Cancer Institute of New Jersey
- Riverview Medical Center/Booker Cancer Center
- Overlook Hospital
- 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
- NYU Winthrop Hospital
- Laura and Isaac Perlmutter Cancer Center at NYU Langone
- NYP/Weill Cornell Medical Center
- 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
- Southeastern Medical Oncology Center-Clinton
- Duke University Medical Center
- Southeastern Medical Oncology Center-Goldsboro
- Wayne Memorial Hospital
- Margaret R Pardee Memorial Hospital
- Onslow Memorial Hospital
- Southeastern Medical Oncology Center-Jacksonville
- FirstHealth of the Carolinas-Moore Regional Hospital
- 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
- Trinity Cancer Care Center
- Indu and Raj Soin Medical Center
- Strecker Cancer Center-Belpre
- Saint Elizabeth Boardman Hospital
- Cleveland Clinic Mercy Hospital
- Mercy Hematology and Oncology Associates Inc
- Dayton Physicians LLC-Miami Valley South
- Miami Valley Hospital South
- Adena Regional Medical Center
- Good Samaritan Hospital - Cincinnati
- Oncology Hematology Care Inc-Kenwood
- Bethesda North Hospital
- TriHealth Cancer Institute-Westside
- TriHealth Cancer Institute-Anderson
- MetroHealth Medical Center
- 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
- 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
- OhioHealth Mansfield Hospital
- Marietta Memorial Hospital
- OhioHealth Marion General Hospital
- Knox Community Hospital
- Licking Memorial Hospital
- Newark Radiation Oncology
- Mercy Health Perrysburg Cancer Center
- Southern Ohio Medical Center
- Springfield Regional Cancer Center
- Springfield Regional Medical Center
- ProMedica Flower Hospital
- ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital
- Mercy Health - Saint Anne Hospital
- Toledo Clinic Cancer Centers-Toledo
- Dayton Physicians LLC - Troy
- Upper Valley Medical Center
- Saint Joseph Warren Hospital
- Saint Ann's Hospital
- 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
- Kaiser Permanente Northwest
- Oregon Health and Science University
- Saint Charles Health System-Redmond
- Salem Hospital
- Lehigh Valley Hospital-Cedar Crest
- Lehigh Valley Hospital - Muhlenberg
- Bryn Mawr Hospital
- Christiana Care Health System-Concord Health Center
- Chambersburg Hospital
- Main Line Health Center-Collegeville
- Geisinger Medical Center
- Pocono Medical Center
- Ephrata Cancer Center
- Ephrata Community Hospital
- Main Line Health Center-Exton
- Adams Cancer Center
- Cherry Tree Cancer Center
- Geisinger Medical Center-Cancer Center Hazleton
- Lehigh Valley Hospital-Hazleton
- Penn State Milton S Hershey Medical Center
- Sechler Family Cancer Center
- Geisinger Medical Oncology-Lewisburg
- Lewistown Hospital
- Riddle Memorial Hospital
- Paoli Memorial Hospital
- Thomas Jefferson University Hospital
- Pottstown Hospital
- Geisinger Cancer Services-Pottsville
- Community Medical Center
- Geisinger Medical Oncology-Selinsgrove
- Geisinger Medical Group
- Geisinger Wyoming Valley/Henry Cancer Center
- Asplundh Cancer Pavilion
- Lankenau Medical Center
- WellSpan Health-York Cancer Center
- WellSpan Health-York Hospital
- Smilow Cancer Hospital Care Center - Westerly
- 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
- Self Regional Healthcare
- Prisma Health Cancer Institute - Greer
- Gibbs Cancer Center-Pelham
- 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
- Pulmonary Medicine Center of Chattanooga-Hixson
- Memorial GYN Plus
- The Don and Sybil Harrington Cancer Center
- Saint Joseph Regional Cancer Center
- Dallas VA Medical Center
- UT Southwestern/Simmons Cancer Center-Dallas
- 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
- Inova Schar Cancer Institute
- Inova Fairfax Hospital
- 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
- FHCC South Lake Union
- Fred Hutchinson Cancer Research Center
- Kaiser Permanente Washington
- Swedish Medical Center-Cherry Hill
- Swedish Medical Center-First Hill
- FHCC at Northwest Hospital
- University of Washington Medical Center - Montlake
- 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
- West Virginia University Charleston Division
- Langlade Hospital and Cancer Center
- ThedaCare Regional Cancer Center
- Duluth Clinic Ashland
- Northwest Wisconsin Cancer Center
- Ascension Southeast Wisconsin Hospital - Elmbrook Campus
- Aurora Cancer Care-Southern Lakes VLCC
- Marshfield Clinic-Chippewa Center
- Aurora Saint Luke's South Shore
- 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
- Aurora Health Care Germantown Health Center
- Aurora Cancer Care-Grafton
- Bellin Memorial Hospital
- 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
- Marshfield Clinic - Ladysmith 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 Columbia Saint Mary's Hospital - Milwaukee
- Aurora Saint Luke's Medical Center
- Medical College of Wisconsin
- Aurora Sinai Medical Center
- Marshfield Clinic-Minocqua Center
- ProHealth D N Greenwald Center
- Cancer Center of Western Wisconsin
- ProHealth Oconomowoc Memorial Hospital
- Saint Vincent Hospital Cancer Center at Oconto Falls
- Vince Lombardi Cancer Clinic - Oshkosh
- Ascension All Saints Hospital
- Aurora Cancer Care-Racine
- Marshfield Medical Center-Rice Lake
- HSHS Saint Nicholas Hospital
- Vince Lombardi Cancer Clinic-Sheboygan
- 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
- Aspirus Regional Cancer Center
- Marshfield Clinic-Wausau 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
- Shaare Zedek Medical Center
Arms of the Study
Arm 1
Arm 2
Experimental
Active Comparator
Arm A (ibrutinib, obinutuzumab, venetoclax)
Arm B (ibrutinib, obinutuzumab)
Patients receive ibrutinib PO daily on days 1-28 and obinutuzumab IV over 4 hours on days 1, 2, 8, and 15 of cycle 1 and on day 1 of cycles 2-6. Patients also receive venetoclax PO QD on days 1-28 of cycles 3-14. Treatment repeats every 28 days for up to 19 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo biopsy and CT scans before and after treatment and collection of blood throughout the study.
Patients receive ibrutinib PO and obinutuzumab as in arm A. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo biopsy and CT scans before and after treatment and collection of blood throughout the study.