Rituximab and Bendamustine Hydrochloride, Rituximab and Ibrutinib, or Ibrutinib Alone in Treating Older Patients With Previously Untreated Chronic Lymphocytic Leukemia
Stage I Chronic Lymphocytic Leukemia, Stage II Chronic Lymphocytic Leukemia, Stage III Chronic Lymphocytic Leukemia
About this trial
This is an interventional treatment trial for Stage I Chronic Lymphocytic Leukemia
Eligibility Criteria
Inclusion Criteria:
- PRE-REGISTRATION (STEP 0)
- All patients are REQUIRED to be pre-registered to A041202 in order to submit peripheral blood to the Alliance Hematologic Malignancy Biorepository (HEME) for central Zap-70 methylation. This specimen submission is mandatory prior to registration as results will be used for stratification
- REGISTRATION (STEP 1)
Patients must be diagnosed with CLL in accordance with International Workshop on Chronic Lymphocytic Leukemia (IWCLL) 2008 criteria that includes all of the following:
- >= 5 x 10^9 B lymphocytes (5000/uL) in the peripheral blood
- On morphologic review, the leukemic cells must be small mature lymphocytes, and prolymphocytes must not exceed 55% of the blood lymphocytes
- CLL 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
- Intermediate risk (formerly Rai stage I/II) is defined by lymphocytosis plus enlarged lymph nodes at any site, with or without hepatomegaly or splenomegaly
- High risk (formerly Rai stage III/IV) is defined by lymphocytosis with or without enlarged nodes and spleen plus disease-related anemia (hemoglobin < 11 g/dL) or thrombocytopenia (platelet count < 100 x 10^9/L) that is not attributable to autoimmune hemolytic anemia or thrombocytopenia
Patients must meet criteria for treatment as defined by IWCLL 2008 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
- Autoimmune anemia and/or thrombocytopenia that is poorly responsive to standard therapy
Constitutional symptoms, which include any of the following:
- Unintentional weight loss of 10% or more within 6 months
- Significant fatigue
- Fevers > 100.5 degrees F for 2 weeks or more without evidence of infection
- Night sweats > 1 month without evidence of infection
- Age >= 65 years
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2
Patients with active hepatitis B defined by hepatitis B surface antigen positivity or core antibody positivity in the presence of hepatitis B DNA are not eligible for this study; patients with a positive hepatitis B core antibody but with negative hepatitis B DNA may participate, but must have hepatitis serologies and hepatitis B DNA monitored periodically by the treating physician
- Intravenous immunoglobulin (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 DNA) they may still participate in the study, but should have hepatitis serologies and hepatitis B DNA monitored periodically by the treating physician
- 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 with known human immunodeficiency virus (HIV) are eligible if their CD4 count is >= 350 cells/mm^3 and if they are not taking prohibited CYP-interacting medications
- Patients may not have had major surgery within 10 days of enrollment, or minor surgery within 7 days of enrollment; examples of minor surgery include dental surgery, insertion of a venous access device, skin biopsy, or aspiration of a joint; the decision about whether a surgery is major or minor can be made at the discretion of the treating physician
- Absolute neutrophil count (ANC) >= 1,000/uL unless due to bone marrow involvement
- Aspartate aminotransferase (AST) or alanine aminotransferase (AST) =< 2.5 x upper limits of normal except if due to disease infiltration of the liver
- Bilirubin =< 1.5 x upper limits of normal (unless due to liver involvement, hemolysis, or Gilbert's disease)
Creatinine clearance >= 40 mL/min
- To be calculated by modified Cockcroft-Gault formula
- Platelet count (untransfused) >= 30,000/uL
Exclusion Criteria:
Prior treatment
- Patients must not have had prior therapy for CLL (except palliative steroids or treatment of autoimmune complications of CLL with rituximab or steroids)
- Treatment with rituximab and/or high dose corticosteroids for autoimmune complications of CLL 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
- Patients must not be receiving active systemic anticoagulation with heparin or warfarin; patients must be off warfarin therapy for at least 30 days prior to enrollment
- Patients must not have any history of Richter's transformation or prolymphocytic leukemia (prolymphocytes in blood > 55%)
- 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 continued requirement for therapy with a strong cytochrome P450 3A4/5 (CYP3A4/5) inhibitor or inducer
- Patients must not have a known allergy to mannitol
- Patients must not have prior significant hypersensitivity to rituximab (not including infusion reactions)
Sites / Locations
- University of Alabama at Birmingham Cancer Center
- Anchorage Radiation Therapy Center
- Alaska Breast Care and Surgery LLC
- Alaska Oncology and Hematology LLC
- Alaska Regional Hospital
- Alaska Women's Cancer Care
- Anchorage Oncology Centre
- Katmai Oncology Group
- Providence Alaska Medical Center
- Mayo Clinic Hospital in Arizona
- Mayo Clinic in Arizona
- Banner University Medical Center - Tucson
- University of Arizona Cancer Center-North Campus
- Yuma Regional Medical Center
- CHI Saint Vincent Cancer Center Hot Springs
- NEA Baptist Memorial Hospital and Fowler Family Cancer Center - Jonesboro
- Kaiser Permanente-Anaheim
- Kaiser Permanente-Deer Valley Medical Center
- PCR Oncology
- Sutter Auburn Faith Hospital
- Sutter Cancer Centers Radiation Oncology Services-Auburn
- Kaiser Permanente-Baldwin Park
- Kaiser Permanente-Bellflower
- Alta Bates Summit Medical Center-Herrick Campus
- Providence Saint Joseph Medical Center/Disney Family Cancer Center
- Mills-Peninsula Medical Center
- Sutter Cancer Centers Radiation Oncology Services-Cameron Park
- John Muir Medical Center-Concord Campus
- Sutter Davis Hospital
- City of Hope Comprehensive Cancer Center
- Kaiser Permanente-Fontana
- Kaiser Permanente-Fremont
- Kaiser Permanente-Fresno
- Marin Cancer Care Inc
- Marin General Hospital
- Kaiser Permanente - Harbor City
- Kaiser Permanente-Irvine
- Kaiser Permanente Los Angeles Medical Center
- Kaiser Permanente West Los Angeles
- Cedars Sinai Medical Center
- Memorial Medical Center
- Kaiser Permanente-Modesto
- Palo Alto Medical Foundation-Camino Division
- Palo Alto Medical Foundation-Gynecologic Oncology
- Sutter Cancer Research Consortium
- Kaiser Permanente-Oakland
- Palo Alto Medical Foundation Health Care
- Stanford Cancer Institute Palo Alto
- Kaiser Permanente - Panorama City
- Kaiser Permanente-Redwood City
- Kaiser Permanente-Richmond
- Kaiser Permanente-Riverside
- Kaiser Permanente-Roseville
- Sutter Cancer Centers Radiation Oncology Services-Roseville
- Sutter Roseville Medical Center
- Sutter Medical Center Sacramento
- Kaiser Permanente-South Sacramento
- Kaiser Permanente - Sacramento
- Saint Helena Hospital
- Kaiser Permanente-San Diego Zion
- Naval Medical Center -San Diego
- California Pacific Medical Center-Pacific Campus
- Kaiser Permanente-San Francisco
- Kaiser Permanente-Santa Teresa-San Jose
- Stanford Cancer Center South Bay
- Kaiser Permanente San Leandro
- Kaiser Permanente-San Marcos
- Kaiser Permanente-San Rafael
- Kaiser Permanente Medical Center - Santa Clara
- Palo Alto Medical Foundation-Santa Cruz
- Kaiser Permanente-Santa Rosa
- Sutter Pacific Medical Foundation
- Kaiser Permanente-South San Francisco
- Kaiser Permanente-Stockton
- Palo Alto Medical Foundation-Sunnyvale
- Northbay Cancer Center
- Sutter Cancer Centers Radiation Oncology Services-Vacaville
- Kaiser Permanente Medical Center-Vacaville
- Kaiser Permanente-Vallejo
- Sutter Solano Medical Center/Cancer Center
- Kaiser Permanente-Walnut Creek
- John Muir Medical Center-Walnut Creek
- Presbyterian Intercommunity Hospital
- Kaiser Permanente-Woodland Hills
- Rocky Mountain Cancer Centers-Aurora
- The Medical Center of Aurora
- Boulder Community Hospital
- Rocky Mountain Cancer Centers-Boulder
- Penrose-Saint Francis Healthcare
- Rocky Mountain Cancer Centers-Penrose
- Denver Health Medical Center
- Kaiser Permanente-Franklin
- 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 States Cancer Research NCORP
- Mercy Medical Center
- Southwest Oncology PC
- Mountain Blue Cancer Care Center - Swedish
- Swedish Medical Center
- Poudre Valley Hospital
- Mountain Blue Cancer Care Center
- National Jewish Health-Western Hematology Oncology
- North Colorado Medical Center
- Rocky Mountain Cancer Centers-Greenwood Village
- 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
- Rocky Mountain Cancer Centers-Thornton
- SCL Health Lutheran Medical Center
- Danbury Hospital
- Smilow Cancer Hospital-Derby Care Center
- Smilow Cancer Hospital Care Center-Fairfield
- Smilow Cancer Hospital Care Center - Guilford
- Smilow Cancer Hospital Care Center at Saint Francis
- Middlesex Hospital
- The Hospital of Central Connecticut
- Yale University
- Yale-New Haven Hospital North Haven Medical Center
- Norwalk Hospital
- Smilow Cancer Hospital-Orange Care Center
- Smilow Cancer Hospital-Torrington 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 Medical Center
- Christiana Gynecologic Oncology LLC
- 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
- MedStar Georgetown University Hospital
- MedStar Washington Hospital Center
- AdventHealth Altamonte
- UM Sylvester Comprehensive Cancer Center at Deerfield Beach
- Holy Cross Hospital
- Baptist MD Anderson Cancer Center
- Jupiter Medical Center
- AdventHealth Kissimmee
- Mount Sinai Medical Center
- University of Miami Miller School of Medicine-Sylvester Cancer Center
- AdventHealth Medical Group Urology at Orlando
- AdventHealth Orlando
- Orlando Health Cancer Institute
- AdventHealth East Orlando
- Sacred Heart Hospital
- UM Sylvester Comprehensive Cancer Center at Plantation
- Cleveland Clinic-Weston
- AdventHealth Winter Park
- Emory University Hospital/Winship Cancer Institute
- Northside Hospital
- John B Amos Cancer Center
- Northside Hospital-Forsyth
- Pali Momi Medical Center
- Queen's Cancer Center - Pearlridge
- The Cancer Center of Hawaii-Pali Momi
- Hawaii Cancer Care Inc - Waterfront Plaza
- 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
- Kootenai Health - Coeur d'Alene
- Saint Luke's Cancer Institute - Fruitland
- Saint Luke's Cancer Institute - Meridian
- Saint Luke's Cancer Institute - Nampa
- Kootenai Clinic Cancer Services - Post Falls
- Kootenai Cancer Clinic
- Saint Luke's Cancer Institute - Twin Falls
- Rush - Copley Medical Center
- Saint Joseph Medical Center
- Illinois CancerCare-Bloomington
- Illinois CancerCare-Canton
- Memorial Hospital of Carbondale
- Illinois CancerCare-Carthage
- Centralia Oncology Clinic
- Northwestern University
- University of Illinois
- University of Chicago Comprehensive Cancer Center
- Carle at The Riverfront
- Cancer Care Specialists of Illinois - Decatur
- Decatur Memorial Hospital
- Heartland Cancer Research NCORP
- Carle Physician Group-Effingham
- Crossroads Cancer Center
- Ascension Alexian Brothers - Elk Grove Village
- 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
- Hematology Oncology Associates of Illinois-Highland Park
- NorthShore University HealthSystem-Highland Park Hospital
- Hinsdale Hematology Oncology Associates Incorporated
- Duly Health and Care Joliet
- Presence Saint Mary's Hospital
- Illinois CancerCare-Kewanee Clinic
- AMG Libertyville - Oncology
- Illinois CancerCare-Macomb
- Carle Physician Group-Mattoon/Charleston
- Loyola University Medical Center
- Illinois CancerCare-Monmouth
- Good Samaritan Regional Health Center
- UC Comprehensive Cancer Center at Silver Cross
- Carle Cancer Institute Normal
- Cancer Care Center of O'Fallon
- Illinois CancerCare-Ottawa Clinic
- Ottawa Regional Hospital and Healthcare Center
- Radiation Oncology of Northern Illinois
- Illinois CancerCare-Pekin
- OSF Saint Francis Radiation Oncology at Pekin Cancer Treatment Center
- Proctor Hospital
- 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
- Quincy Medical Group-Clinic
- SwedishAmerican Regional Cancer Center/ACT
- North Shore Medical Center
- Central Illinois Hematology Oncology Center
- Southern Illinois University School of Medicine
- Springfield Clinic
- Memorial Medical Center
- Carle Cancer Center
- The Carle Foundation Hospital
- Northwestern Medicine Cancer Center Warrenville
- Rush-Copley Healthcare Center
- Michiana Hematology Oncology PC-Crown Point
- Elkhart Clinic
- Michiana Hematology Oncology PC-Elkhart
- Elkhart General Hospital
- Fort Wayne Medical Oncology and Hematology Inc-Parkview
- Community Howard Regional Health
- IU Health La Porte Hospital
- Franciscan Saint Anthony Health-Michigan City
- Woodland Cancer Care Center
- Memorial Regional Cancer Center Day Road
- Michiana Hematology Oncology PC-Mishawaka
- Saint Joseph Regional Medical Center-Mishawaka
- Michiana Hematology Oncology PC-Plymouth
- Reid Health
- Memorial Hospital of South Bend
- Michiana Hematology Oncology PC-South Bend
- Northern Indiana Cancer Research Consortium
- Michiana Hematology Oncology PC-Westville
- Mary Greeley Medical Center
- McFarland Clinic - Ames
- 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
- Iowa-Wide Oncology Research Coalition NCORP
- Mercy Medical Center - Des Moines
- Mission Cancer and Blood - Laurel
- McFarland Clinic - Trinity Cancer Center
- University of Iowa/Holden Comprehensive Cancer Center
- Iowa City VA Healthcare System
- McFarland Clinic - Jefferson
- McFarland Clinic - Marshalltown
- Mercy Medical Center - North Iowa
- Siouxland Regional Cancer Center
- Mercy Medical Center-Sioux City
- Saint Luke's Regional Medical Center
- Abben Cancer Center
- MercyOne Waterloo Cancer Center
- Mercy Medical Center-West Lakes
- Cancer Center of Kansas - Chanute
- Cancer Center of Kansas - Dodge City
- Cancer Center of Kansas - El Dorado
- Newman Regional Health
- Cancer Center of Kansas - Fort Scott
- Saint Catherine Hospital
- Saint Rose Ambulatory and Surgery Center
- HaysMed University of Kansas Health System
- Cancer Center of Kansas-Independence
- University of Kansas Cancer Center-West
- University of Kansas Cancer Center
- Cancer Center of Kansas-Kingman
- Lawrence Memorial Hospital
- Cancer Center of Kansas-Liberal
- Cancer Center of Kansas - Newton
- Olathe Health Cancer Center
- Menorah Medical Center
- University of Kansas Cancer Center-Overland Park
- Saint Luke's South Hospital
- Cancer Center of Kansas - Parsons
- Ascension Via Christi - Pittsburg
- Kansas City NCI Community Oncology Research Program
- Cancer Center of Kansas - Pratt
- Cancer Center of Kansas - Salina
- Salina Regional Health Center
- Cotton O'Neil Cancer Center / Stormont Vail Health
- University of Kansas Health System Saint Francis Campus
- Cancer Center of Kansas - Wellington
- Associates In Womens Health
- Cancer Center of Kansas-Wichita Medical Arts Tower
- Ascension Via Christi Hospitals Wichita
- Cancer Center of Kansas - Wichita
- Cancer Center of Kansas - Winfield
- Flaget Memorial Hospital
- Commonwealth Cancer Center-Corbin
- Oncology Hematology Care Inc-Crestview
- Saint Joseph Radiation Oncology Resource Center
- Saint Joseph Hospital East
- Jewish Hospital
- Saints Mary and Elizabeth Hospital
- UofL Health Medical Center Northeast
- Jewish Hospital Medical Center South
- LSU Health Baton Rouge-North Clinic
- Louisiana Hematology Oncology Associates LLC
- Mary Bird Perkins Cancer Center
- Ochsner Health Center-Summa
- Our Lady of the Lake Physicians Group - Medical Oncology
- Mary Bird Perkins Cancer Center - Covington
- Mary Bird Perkins Cancer Center - Houma
- Ochsner Medical Center Kenner
- Ochsner Medical Center Jefferson
- Harold Alfond Center for Cancer Care
- Eastern Maine Medical Center
- Lafayette Family Cancer Center-EMMC
- Penobscot Bay Medical Center
- York Hospital
- Greater Baltimore Medical Center
- Sinai Hospital of Baltimore
- Saint Agnes Hospital
- MedStar Franklin Square Medical Center/Weinberg Cancer Institute
- UPMC Western Maryland
- Frederick Memorial Hospital
- Northwest Hospital Center
- TidalHealth Peninsula Regional
- Beverly Hospital
- Tufts Medical Center
- Massachusetts General Hospital Cancer Center
- Brigham and Women's Hospital
- Boston Medical Center
- Dana-Farber Cancer Institute
- Lahey Hospital and Medical Center
- Simonds-Sinon Regional Cancer Center
- Addison Gilbert Hospital
- Newton-Wellesley Hospital
- D'Amour Center for Cancer Care
- Baystate Medical Center
- Winchester Hospital
- UMass Memorial Medical Center - University Campus
- Bixby Medical Center
- Hickman Cancer Center
- Michigan Cancer Research Consortium NCORP
- Saint Joseph Mercy Hospital
- Bronson Battle Creek
- McLaren Cancer Institute-Bay City
- Henry Ford Cancer Institute-Downriver
- McLaren Cancer Institute-Clarkston
- Henry Ford Macomb Hospital-Clinton Township
- Huron Valley-Sinai Hospital
- Beaumont Hospital - Dearborn
- Henry Ford Medical Center-Fairlane
- Wayne State University/Karmanos Cancer Institute
- Henry Ford Hospital
- Ascension Saint John Hospital
- Green Bay Oncology - Escanaba
- Weisberg Cancer Treatment Center
- Beaumont Hospital - Farmington Hills
- Genesys Hurley Cancer Institute
- Hurley Medical Center
- Singh and Arora Hematology Oncology PC
- Cancer Research Consortium of West Michigan NCORP
- Spectrum Health at Butterworth Campus
- Trinity Health Grand Rapids Hospital
- William Beaumont Hospital-Grosse Pointe
- Green Bay Oncology - Iron Mountain
- Allegiance Health
- West Michigan Cancer Center
- Karmanos Cancer Institute at McLaren Greater Lansing
- Sparrow Hospital
- McLaren Cancer Institute-Lapeer Region
- Trinity Health Saint Mary Mercy Livonia Hospital
- Mercy Memorial Hospital
- Toledo Clinic Cancer Centers-Monroe
- McLaren Cancer Institute-Macomb
- McLaren Cancer Institute-Central Michigan
- Trinity Health Muskegon Hospital
- Ascension Providence Hospitals - Novi
- Henry Ford Medical Center-Columbus
- McLaren Cancer Institute-Northern Michigan
- Saint Joseph Mercy Oakland
- Lake Huron Medical Center
- Spectrum Health Reed City Hospital
- 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
- Ascension Providence Hospitals - Southfield
- Premier Hematology Oncology Care
- Mitchell Folbe MD PC
- Munson Medical Center
- Michigan Institute of Urology-Town Center
- Claudia BR Herke MD PC
- William Beaumont Hospital - Troy
- Hematology Oncology Consultants PC-Troy
- Saint John Macomb-Oakland Hospital
- Henry Ford West Bloomfield Hospital
- Sanford Joe Lueken Cancer Center
- Essentia Health Saint Joseph's Medical Center
- Fairview Ridges Hospital
- Mercy Hospital
- Essentia Health Cancer Center
- Essentia Health Saint Mary's Medical Center
- Miller-Dwan Hospital
- Saint Luke's Hospital of Duluth
- Fairview Southdale Hospital
- Lake Region Healthcare Corporation-Cancer Care
- Unity Hospital
- Hutchinson Area Health Care
- Minnesota Oncology Hematology PA-Maplewood
- Saint John's Hospital - Healtheast
- Abbott-Northwestern Hospital
- Hennepin County Medical Center
- Minneapolis VA Medical Center
- Health Partners Inc
- New Ulm Medical Center
- North Memorial Medical Health Center
- Mayo Clinic in Rochester
- Coborn Cancer Center at Saint Cloud Hospital
- Saint Cloud Hospital
- Metro Minnesota Community Oncology Research Consortium
- Park Nicollet Clinic - Saint Louis Park
- Regions Hospital
- United Hospital
- Saint Francis Regional Medical Center
- Lakeview Hospital
- Ridgeview Medical Center
- Rice Memorial Hospital
- Minnesota Oncology Hematology PA-Woodbury
- University of Mississippi Medical Center
- 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
- Centerpoint Medical Center LLC
- Capital Region Southwest Campus
- Freeman Health System
- Mercy Hospital Joplin
- Truman Medical Centers
- Saint Luke's Hospital of Kansas City
- North Kansas City Hospital
- Heartland Hematology and Oncology Associates Incorporated
- The University of Kansas Cancer Center-South
- Research Medical Center
- University of Kansas Cancer Center - North
- University of Kansas Cancer Center - Lee's Summit
- Saint Luke's East - Lee's Summit
- Liberty Radiation Oncology Center
- 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
- Siteman Cancer Center-South County
- Missouri Baptist Medical Center
- 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
- Billings Clinic Cancer Center
- Saint Vincent Healthcare
- Montana Cancer Consortium NCORP
- Bozeman Deaconess Hospital
- Saint James Community Hospital and Cancer Treatment Center
- Benefis Healthcare- Sletten Cancer Institute
- 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
- University of Nebraska Medical Center
- Midlands Community Hospital
- Cancer and Blood Specialists-Henderson
- Comprehensive Cancer Centers of Nevada - Henderson
- Las Vegas Cancer Center-Henderson
- Comprehensive Cancer Centers of Nevada-Southeast Henderson
- GenesisCare USA - Henderson
- Cancer and Blood Specialists-Shadow
- Radiation Oncology Centers of Nevada Central
- GenesisCare USA - Las Vegas
- HealthCare Partners Medical Group Oncology/Hematology-Maryland Parkway
- HealthCare Partners Medical Group Oncology/Hematology-San Martin
- Radiation Oncology Centers of Nevada Southeast
- Cancer Therapy and Integrative Medicine
- Cancer and Blood Specialists-Tenaya
- Comprehensive Cancer Centers of Nevada - Northwest
- GenesisCare USA - Vegas Tenaya
- HealthCare Partners Medical Group Oncology/Hematology-Tenaya
- Alliance for Childhood Diseases/Cure 4 the Kids Foundation
- 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
- Nevada Cancer Research Foundation NCORP
- Saint Mary's Regional Medical Center
- New Hampshire Oncology Hematology PA-Concord
- Parkland Medical Center
- Wentworth-Douglass Hospital
- LRGHealthcare-Lakes Region General Hospital
- Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center
- Norris Cotton Cancer Center-Manchester
- Solinsky Center for Cancer Care
- Dartmouth Cancer Center - Nashua
- Portsmouth Regional Hospital
- Veterans Adminstration New Jersey Health Care System
- Englewood Hospital and Medical Center
- Rutgers Cancer Institute of New Jersey
- Newark Beth Israel Medical Center
- The Valley Hospital-Luckow Pavilion
- Penn Medicine Princeton Health
- Valley Hospital
- Overlook Hospital
- Valley Health System-Hematology/Oncology
- University of New Mexico Cancer Center
- Presbyterian Kaseman Hospital
- Memorial Medical Center - Las Cruces
- Hematology Oncology Associates of Central New York-Auburn
- Maimonides Medical Center
- Roswell Park Cancer Institute
- Hematology Oncology Associates of Central New York-East Syracuse
- Glens Falls Hospital
- Northwell Health/Center for Advanced Medicine
- North Shore University Hospital
- Garnet Health Medical Center
- NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
- Champlain Valley Physicians Hospital Medical Center
- University of Rochester
- Hematology Oncology Associates of Central New York-Rome
- Stony Brook University Medical Center
- State University of New York Upstate Medical University
- Hematology Oncology Associates of Central New York-Onondaga Hill
- Faxton-Saint Luke's Healthcare
- Mission Hospital
- Mountain Radiation Oncology PA
- AdventHealth Infusion Center Asheville
- Messino Cancer Centers
- Hope Women's Cancer Centers-Asheville
- Transylvania Regional Hospital
- UNC Lineberger Comprehensive Cancer Center
- Sampson Radiation Oncology
- Southeastern Medical Oncology Center-Clinton
- Duke University Medical Center
- Angel Medical Center
- Southeastern Medical Oncology Center-Goldsboro
- Wayne Memorial Hospital
- Wayne Radiation Oncology
- East Carolina University
- Hendersonville Hematology and Oncology at Pardee
- Margaret R Pardee Memorial Hospital
- AdventHealth Hendersonville
- Onslow Memorial Hospital
- Southeastern Medical Oncology Center-Jacksonville
- Vidant Oncology-Kinston
- Mission Hospital McDowell
- FirstHealth of the Carolinas-Moore Regional Hospital
- Blue Ridge Regional Hospital
- Iredell Memorial Hospital
- Southeast Clinical Oncology Research Consortium NCORP
- Wake Forest University Health Sciences
- Sanford Bismarck Medical Center
- Essentia Health Cancer Center-South University Clinic
- Sanford Broadway Medical Center
- Sanford Clinic North-Fargo
- Sanford Roger Maris Cancer Center
- Altru Cancer Center
- Trinity Cancer Care Center
- Cleveland Clinic Akron General
- Cleveland Clinic Cancer Center Beachwood
- UHHS-Chagrin Highlands Medical Center
- Strecker Cancer Center-Belpre
- Toledo Clinic Cancer Centers-Bowling Green
- Miami Valley Hospital South
- Geauga Hospital
- Adena Regional Medical Center
- Oncology Hematology Care Inc-Eden Park
- Oncology Hematology Care Inc-Mercy West
- University of Cincinnati Cancer Center-UC Medical Center
- Good Samaritan Hospital - Cincinnati
- Oncology Hematology Care Inc-Anderson
- Oncology Hematology Care Inc-Kenwood
- Bethesda North Hospital
- Oncology Hematology Care Inc-Blue Ash
- TriHealth Cancer Institute-Westside
- TriHealth Cancer Institute-Anderson
- Case Western Reserve University
- MetroHealth Medical Center
- Cleveland Clinic Cancer Center/Fairview Hospital
- Cleveland Clinic Foundation
- Ohio State University Comprehensive Cancer Center
- Columbus Oncology and Hematology Associates Inc
- Riverside Methodist Hospital
- Columbus NCI Community Oncology Research Program
- Grant Medical Center
- The Mark H Zangmeister Center
- Mount Carmel Health Center West
- Doctors Hospital
- Good Samaritan Hospital - Dayton
- Miami Valley Hospital
- Miami Valley Hospital North
- Dayton NCI Community Oncology Research Program
- Delaware Health Center-Grady Cancer Center
- Delaware Radiation Oncology
- Grady Memorial Hospital
- Mercy Cancer Center-Elyria
- Oncology Hematology Care Inc-Healthplex
- Blanchard Valley Hospital
- Atrium Medical Center-Middletown Regional Hospital
- Wayne Hospital
- Cleveland Clinic Cancer Center Independence
- Kettering Medical Center
- Fairfield Medical Center
- Lancaster Radiation Oncology
- Lima Memorial Hospital
- Cleveland Clinic Cancer Center Mansfield
- Marietta Memorial Hospital
- Toledo Clinic Cancer Centers-Maumee
- Toledo Radiation Oncology at Northwest Ohio Onocolgy Center
- Hillcrest Hospital Cancer Center
- UH Seidman Cancer Center at Landerbrook Health 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
- Saint Charles Hospital
- Toledo Clinic Cancer Centers-Oregon
- Southern Ohio Medical Center
- North Coast Cancer Care
- Springfield Regional Cancer Center
- Springfield Regional Medical Center
- Cleveland Clinic Cancer Center Strongsville
- ProMedica Flower Hospital
- Mercy Hospital of Tiffin
- ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital
- Saint Vincent Mercy Medical Center
- University of Toledo
- Toledo Community Hospital Oncology Program CCOP
- Mercy Health - Saint Anne Hospital
- Toledo Clinic Cancer Centers-Toledo
- Upper Valley Medical Center
- South Pointe Hospital
- Fulton County Health Center
- University of Cincinnati Cancer Center-West Chester
- 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
- Genesis Healthcare System Cancer Care Center
- Cancer Centers of Southwest Oklahoma Research
- University of Oklahoma Health Sciences Center
- Mercy Hospital Oklahoma City
- Natalie Warren Bryant Cancer Center at Saint Francis
- Oklahoma Cancer Specialists and Research Institute-Tulsa
- Warren Clinic Oncology-Tulsa
- Saint Charles Health System
- Clackamas Radiation Oncology Center
- Providence Cancer Institute Clackamas Clinic
- Bay Area Hospital
- Providence Milwaukie Hospital
- Providence Newberg Medical Center
- Providence Willamette Falls Medical Center
- Providence Portland Medical Center
- Providence Saint Vincent Medical Center
- Kaiser Permanente Northwest
- Oregon Health and Science University
- Lehigh Valley Hospital-Cedar Crest
- UPMC-Heritage Valley Health System Beaver
- Lehigh Valley Hospital - Muhlenberg
- Bryn Mawr Hospital
- Christiana Care Health System-Concord Health Center
- Geisinger Medical Center
- Delaware County Memorial Hospital
- Pocono Medical Center
- Ephrata Cancer Center
- Ephrata Community Hospital
- Adams Cancer Center
- UPMC Cancer Centers - Arnold Palmer Pavilion
- Cherry Tree Cancer Center
- Geisinger Medical Center-Cancer Center Hazleton
- Penn State Milton S Hershey Medical Center
- UPMC-Johnstown/John P. Murtha Regional Cancer Center
- UPMC Cancer Center at UPMC McKeesport
- Riddle Memorial Hospital
- UPMC Hillman Cancer Center in Coraopolis
- Paoli Memorial Hospital
- Thomas Jefferson University Hospital
- Fox Chase Cancer Center
- Jefferson Torresdale Hospital
- UPMC-Magee Womens Hospital
- UPMC-Presbyterian Hospital
- UPMC-Saint Margaret
- University of Pittsburgh Cancer Institute (UPCI)
- UPMC-Shadyside Hospital
- UPMC Jefferson Regional Radiation Oncology
- UPMC-Passavant Hospital
- UPMC-Saint Clair Hospital Cancer Center
- Geisinger Cancer Services-Pottsville
- Hematology and Oncology Associates of North East Pennsylvania
- UPMC Cancer Center at UPMC Northwest
- Geisinger Medical Group
- UPMC Uniontown Hospital Radiation Oncology
- Associates In Hematology Oncology PC-Upland
- UPMC Washington Hospital Radiation Oncology
- Chester County Hospital
- Reading Hospital
- Geisinger Wyoming Valley/Henry Cancer Center
- UPMC Susquehanna
- Lankenau Medical Center
- WellSpan Health-York Cancer Center
- WellSpan Health-York Hospital
- Memorial Hospital of Rhode Island
- Rhode Island Hospital
- Miriam Hospital
- AnMed Health Cancer Center
- Prisma Health Cancer Institute - Spartanburg
- Roper Hospital
- Charleston Oncology - Roper
- Lowcountry Hematology Oncology PA-North Charleston
- Bon Secours Saint Francis Hospital
- Charleston Oncology - Saint Francis
- Lowcountry Hematology Oncology PA-West Ashley
- Medical University of South Carolina
- Prisma Health Cancer Institute - Easley
- McLeod Regional Medical Center
- Gibbs Cancer Center-Gaffney
- Greenville Health System Cancer Institute-Andrews
- Saint Francis Hospital
- 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
- Carolina Blood and Cancer Care Associates PA-Lancaster
- Lowcountry Hematology Oncology PA-Mount Pleasant
- Carolina Blood and Cancer Care Associates PA
- Prisma Health Cancer Institute - Seneca
- Spartanburg Medical Center
- MGC Hematology Oncology-Union
- Lexington Medical Center
- Rapid City Regional Hospital
- Sanford Cancer Center Oncology Clinic
- Avera Cancer Institute
- Sanford USD Medical Center - Sioux Falls
- Bristol Regional Medical Center
- Wellmont Medical Associates Oncology and Hematology-Bristol
- Erlanger Medical Center
- Memorial Hospital
- Pulmonary Medicine Center of Chattanooga-Hixson
- Ballad Health Cancer Care - Kingsport
- Wellmont Holston Valley Hospital and Medical Center
- Memorial GYN Plus
- The Don and Sybil Harrington Cancer Center
- Parkland Memorial Hospital
- UT Southwestern/Simmons Cancer Center-Dallas
- Cancer Therapy and Research Center at The UT Health Science Center at San Antonio
- University Hospital
- University of Texas Health Science Center at San Antonio
- Southwestern Vermont Medical Center
- Central Vermont Medical Center/National Life Cancer Treatment
- University of Vermont and State Agricultural College
- White River Junction Veteran Administration Medical Center
- University of Virginia Cancer Center
- Fredericksburg Oncology Inc
- Hematology Oncology Associates of Fredericksburg Inc
- Virginia Oncology Associates-Hampton
- Centra Lynchburg Hematology-Oncology Clinic Inc
- Southwest VA Regional Cancer Center
- Virginia Cancer Institute
- Virginia Commonwealth University/Massey Cancer Center
- VCU Community Memorial Health Center
- Shenandoah Oncology PC
- Providence Regional Cancer System-Aberdeen
- Cancer Care Center at Island Hospital
- Swedish Cancer Institute-Eastside Oncology Hematology
- 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
- Saint Francis Hospital
- Swedish Cancer Institute-Issaquah
- Providence Regional Cancer System-Lacey
- Saint Clare Hospital
- PeaceHealth Saint John Medical Center
- Harrison HealthPartners Hematology and Oncology-Poulsbo
- Minor and James Medical PLLC
- Pacific Gynecology Specialists
- Swedish Medical Center-Ballard Campus
- Kaiser Permanente Washington
- Swedish Medical Center-First Hill
- Providence Regional Cancer System-Shelton
- MultiCare Deaconess Cancer and Blood Specialty Center - Valley
- MultiCare Deaconess Cancer and Blood Specialty Center - Downtown
- Evergreen Hematology and Oncology PS
- Franciscan Research Center-Northwest Medical Plaza
- Northwest Medical Specialties PLLC
- 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
- United Hospital Center
- West Virginia University Charleston Division
- Edwards Comprehensive Cancer Center
- Saint Mary's Medical Center
- WVUH-Berkely Medical Center
- West Virginia University Healthcare
- Camden Clark Medical Center
- Langlade Hospital and Cancer Center
- Aurora Cancer Care-Southern Lakes VLCC
- Marshfield Clinic-Chippewa Center
- HSHS Sacred Heart Hospital
- Marshfield Clinic Cancer Center at Sacred Heart
- Aurora Health Center-Fond du Lac
- Aurora Health Care Germantown Health Center
- Aurora Cancer Care-Grafton
- Green Bay Oncology at Saint Vincent Hospital
- Bellin Memorial Hospital
- Saint Vincent Hospital Cancer Center Green Bay
- Green Bay Oncology Limited at Saint Mary's Hospital
- Saint Vincent Hospital Cancer Center at Saint Mary's
- Aurora BayCare Medical Center
- Aurora Cancer Care-Kenosha South
- Gundersen Lutheran Medical Center
- Marshfield Clinic - Ladysmith Center
- Holy Family Memorial Hospital
- Aurora Bay Area Medical Group-Marinette
- Bay Area Medical Center
- Marshfield Medical Center-Marshfield
- Marshfield Medical Center
- Aurora Cancer Care-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
- Aurora Cancer Care-Racine
- Ascension Saint Mary's Hospital
- Saint Mary's Hospital
- Marshfield Medical Center-Rice Lake
- HSHS Saint Nicholas Hospital
- Vince Lombardi Cancer Clinic-Sheboygan
- Ascension Saint Michael's Hospital
- Green Bay Oncology - Sturgeon Bay
- Aurora Medical Center in Summit
- Vince Lombardi Cancer Clinic-Two Rivers
- Aurora Cancer Care-Waukesha
- ProHealth Waukesha Memorial Hospital
- UW Cancer Center at ProHealth Care
- Aspirus Regional Cancer Center
- Marshfield Clinic-Wausau Center
- Aurora Cancer Care-Milwaukee West
- Aurora West Allis Medical Center
- Ascension Saint Clare's Hospital
- Diagnostic and Treatment Center
- Marshfield Medical Center - Weston
- Aspirus Cancer Care - Wisconsin Rapids
- Marshfield Clinic - Wisconsin Rapids Center
- Rocky Mountain Oncology
- Cheyenne Regional Medical Center-West
- Big Horn Basin Cancer Center
- Billings Clinic-Cody
- Welch Cancer Center
- Tom Baker Cancer Centre
- The Moncton Hospital
- QEII Health Sciences Centre/Nova Scotia Health Authority
- Juravinski Cancer Centre at Hamilton Health Sciences
- Kingston Health Sciences Centre
- London Regional Cancer Program
- Stronach Regional Health Centre at Southlake
- Lakeridge Health Oshawa
- Ottawa Hospital and Cancer Center-General Campus
- Health Sciences North
- Humber River Hospital
- Michael Garron Hospital
- Odette Cancer Centre- Sunnybrook Health Sciences Centre
- University Health Network-Princess Margaret Hospital
- CSSS Champlain-Charles Le Moyne
- CHUM - Hopital Notre-Dame
- McGill University Department of Oncology
- CHUM - Centre Hospitalier de l'Universite de Montreal
- Jewish General Hospital
- Allan Blair Cancer Centre
- Saskatoon Cancer Centre
Arms of the Study
Arm 1
Arm 2
Arm 3
Active Comparator
Experimental
Experimental
Arm I (rituximab, bendamustine hydrochloride)
Arm II (ibrutinib)
Arm III (ibrutinib, rituximab)
Patients receive rituximab IV on day 1 (day 0 course 1) and bendamustine hydrochloride IV over 30 minutes on days 1-2. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients experiencing disease progression may crossover to Arm II.
Patients receive ibrutinib PO daily. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Patients receive ibrutinib as in Arm II. Patients receive rituximab IV on days 1, 8, 15, and 22 of course 2 and on day 1 of courses 3-6. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.