Ibrutinib and Rituximab Compared With Fludarabine Phosphate, Cyclophosphamide, and Rituximab in Treating Patients With Untreated Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma
Anemia, Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma
About this trial
This is an interventional treatment trial for Anemia
Eligibility Criteria
Inclusion Criteria:
Diagnosis of CLL according to the National Cancer Institute (NCI)/Internal 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 x 10^9/L
Immunophenotype consistent with CLL defined as:
- The predominant population of lymphocytes share both B-cell antigens (cluster of differentiation [CD]19, 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 FISH analysis for t(11;14)(immunoglobulin heavy locus [IgH]/cyclin D1 [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, Bruton's tyrosine kinase (BTK) inhibitor therapy, 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 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
- ECOG performance status between 0-2
- Life expectancy of >= 12 months
- Ability to tolerate FCR based therapy
- 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 =< 2.5 x upper limit of normal (ULN) (obtained =< 14 days prior to registration) unless due to Gilbert's disease; for those with a total bilirubin > 2.5 x ULN, a direct bilirubin should be performed and must be < 1.5 mg/dL for Gilbert's to be diagnosed
- If value is higher due to hepatic involvement by CLL, patient is eligible
Serum glutamic oxaloacetic transaminase (SGOT) (aspartate transaminase [AST])/serum glutamate-pyruvate transaminase (SGPT) (alanine transaminase [ALT]) =< 3.0 x the institutional ULN (obtained =< 14 days prior to registration)
- 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)
- If value is higher due to hepatic involvement by CLL, patient is eligible
- 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) used for treatment of non-hematologic medical condition (e.g. chronic adrenal insufficiency) is permitted
- No previous use of corticosteroids for autoimmune complications that have developed since the initial diagnosis of CLL; 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, they must not 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 the last 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
Patients with human immunodeficiency virus (HIV) infection may be eligible provided they meet the following criteria:
- CD4-positive cell count >= lower limit of institutional normal
- HIV viral load < 10,000 copies HIV ribonucleic acid (RNA)/mL (if not on anti-HIV therapy) OR < 50 copies HIV RNA/mL (if on anti-HIV therapy)
- No evidence of hepatitis B or C infection
- No evidence of resistant strains of HIV
- No history of acquired immune deficiency syndrome (AIDS)-defining condition
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
- Serologic status reflecting active hepatitis B or C infection; patients that are positive for hepatitis B core antibody, hepatitis B surface antigen (HBsAg), or hepatitis C antibody must have a negative polymerase chain reaction (PCR) prior to enrollment (PCR positive patients will be excluded)
- Patients are not eligible if they require treatment with a strong cytochrome P450 (CYP) family 3, subfamily A (3A) inhibitor
- 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 an investigational agent whose genotoxic, mutagenic, and teratogenic effects on the developing fetus and newborn are unknown; female patients of childbearing potential must have a negative serum pregnancy test within 2 weeks prior to registration to rule out pregnancy; female patients who are of non-reproductive potential are those who are post-menopausal by history (i.e. no menses for >= 1 year); OR history of hysterectomy; OR history of bilateral tubal ligation; OR history of bilateral oophorectomy)
- Women of childbearing potential and sexually active males must be strongly advised to use an accepted and effective method of contraception or to abstain from sexual intercourse for 90 days after the last dose of study drug
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 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)
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 Regional Hospital
- Alaska Women's Cancer Care
- Anchorage Oncology Centre
- Katmai Oncology Group
- Providence Alaska Medical Center
- Fairbanks Memorial Hospital
- Mayo Clinic in Arizona
- CHI Saint Vincent Cancer Center Hot Springs
- NEA Baptist Memorial Hospital and Fowler Family Cancer Center - Jonesboro
- University of Arkansas for Medical Sciences
- 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
- Eden Hospital Medical Center
- Adventist Health Cancer Care Center Chico
- John Muir Medical Center-Concord Campus
- Sutter Davis Hospital
- 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
- 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
- UC Irvine Health/Chao Family Comprehensive Cancer Center
- 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
- Kaiser Permanente-San Diego Mission
- Kaiser Permanente-San Diego Zion
- 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
- Pacific Central Coast Health Center-San Luis Obispo
- 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
- 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
- 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
- National Jewish Health-Main Campus
- 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
- 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
- Smilow Cancer Hospital-Derby Care Center
- Smilow Cancer Hospital Care Center-Fairfield
- Smilow Cancer Hospital Care Center at Saint Francis
- Middlesex Hospital
- 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-Torrington Care Center
- Smilow Cancer Hospital Care Center-Trumbull
- Smilow Cancer Hospital-Waterbury Care Center
- 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
- Baptist MD Anderson Cancer Center
- Lakeland Regional Health Hollis Cancer Center
- Orlando Health Cancer Institute
- Phoebe Putney Memorial Hospital
- Emory University Hospital/Winship Cancer Institute
- John B Amos Cancer Center
- Central Georgia Gynecologic Oncology
- Medical Center of Central Georgia
- Lewis Cancer and Research Pavilion at Saint Joseph's/Candler
- Kaiser Permanente Moanalua Medical Center
- 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 Chicago Comprehensive Cancer Center
- Carle at The Riverfront
- Cancer Care Specialists of Illinois - Decatur
- Decatur Memorial Hospital
- 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
- 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
- Trinity Medical Center
- Good Samaritan Regional Health Center
- UC Comprehensive Cancer Center at Silver Cross
- Illinois Cancer Specialists-Niles
- Carle Cancer Institute Normal
- Cancer Care Center of O'Fallon
- Advocate Christ Medical Center
- Illinois CancerCare-Ottawa Clinic
- Radiation Oncology of Northern Illinois
- 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
- Hematology Oncology Associates of Illinois - Skokie
- 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
- Ascension Saint Vincent Anderson
- Franciscan Saint Anthony Health-Michigan City
- Woodland Cancer Care Center
- Memorial Regional Cancer Center Day Road
- Reid Health
- Memorial Hospital of South Bend
- Mary Greeley Medical Center
- McFarland Clinic - Ames
- McFarland Clinic - Boone
- Medical Oncology and Hematology Associates-West Des Moines
- Mercy Cancer Center-West Lakes
- Alegent Health Mercy Hospital
- Greater Regional Medical Center
- Mercy Medical Center - Des Moines
- Mission Cancer and Blood - Laurel
- McFarland Clinic - Trinity Cancer Center
- 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
- Cancer Center of Kansas - Fort Scott
- Cancer Center of Kansas-Independence
- Cancer Center of Kansas-Kingman
- Lawrence Memorial Hospital
- Kansas Institute of Medicine Cancer and Blood Center
- Minimally Invasive Surgery Hospital
- Cancer Center of Kansas-Liberal
- Cancer Center of Kansas - Newton
- Menorah Medical Center
- Saint Luke's South Hospital
- Cancer Center of Kansas - Parsons
- Kansas City NCI Community Oncology Research Program
- Cancer Center of Kansas - Pratt
- Cancer Center of Kansas - Salina
- Cotton O'Neil Cancer Center / Stormont Vail Health
- 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
- Ochsner Health Center-Summa
- Ochsner Medical Center Kenner
- Ochsner LSU Health Monroe Medical Center
- Ochsner Medical Center Jefferson
- LSU Health Sciences Center at Shreveport
- CHRISTUS Highland Medical Center
- Harold Alfond Center for Cancer Care
- Eastern Maine Medical Center
- Lafayette Family Cancer Center-EMMC
- Penobscot Bay Medical Center
- University of Maryland/Greenebaum Cancer Center
- Saint Agnes Hospital
- Beverly Hospital
- Tufts Medical Center
- Eastern Cooperative Oncology Group
- Lahey Hospital and Medical Center
- Addison Gilbert Hospital
- 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
- Henry Ford Cancer Institute-Downriver
- 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
- Green Bay Oncology - Escanaba
- Weisberg Cancer Treatment Center
- Beaumont Hospital - Farmington Hills
- Genesys Hurley Cancer Institute
- Hurley Medical Center
- William Beaumont Hospital-Grosse Pointe
- Green Bay Oncology - Iron Mountain
- Allegiance Health
- West Michigan Cancer Center
- Sparrow Hospital
- Trinity Health Saint Mary Mercy Livonia Hospital
- Mercy Memorial Hospital
- Monroe Cancer Center
- Toledo Clinic Cancer Centers-Monroe
- Ascension Providence Hospitals - Novi
- Henry Ford Medical Center-Columbus
- Saint Joseph Mercy Oakland
- Lake Huron Medical Center
- 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
- 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
- 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
- Health Partners Inc
- New Ulm Medical Center
- North Memorial Medical Health Center
- Mayo Clinic in Rochester
- 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
- 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
- Centerpoint Medical Center LLC
- Capital Region Southwest Campus
- Freeman Health System
- Mercy Hospital Joplin
- Saint Luke's Hospital of Kansas City
- Heartland Hematology and Oncology Associates Incorporated
- Research Medical Center
- 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
- Community Hospital of Anaconda
- 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
- 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
- Nebraska Hematology and Oncology
- Nebraska Cancer Research Center
- Saint Elizabeth Regional Medical Center
- Southeast Nebraska Cancer Center - 68th Street Place
- Faith Regional Health Services Carson Cancer Center
- Great Plains Health Callahan Cancer Center
- Missouri Valley Cancer Consortium
- Alegent Health Immanuel Medical Center
- Hematology and Oncology Consultants PC
- Alegent Health Bergan Mercy Medical Center
- Nebraska Cancer Specialists - Omaha
- Alegent Health Lakeside Hospital
- Oncology Hematology West PC
- Creighton University Medical Center
- University of Nebraska Medical Center
- Midlands Community Hospital
- Regional West Medical Center Cancer Center
- 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
- 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
- Wentworth-Douglass Hospital
- Veterans Adminstration New Jersey Health Care System
- Newark Beth Israel Medical Center
- University of New Mexico Cancer Center
- New York Oncology Hematology PC - Albany Medical Center
- Hematology Oncology Associates of Central New York-Auburn
- Roswell Park Cancer Institute
- Glens Falls Hospital
- Northwell Health/Center for Advanced Medicine
- Hematology Oncology Associates of Central New York-Liverpool
- North Shore University Hospital
- Garnet Health Medical Center
- Long Island Jewish Medical Center
- University of Rochester
- Hematology Oncology Associates of Central New York-Rome
- State University of New York Upstate Medical University
- Hematology Oncology Associates of Central New York-Onondaga Hill
- Mission Hospital
- AdventHealth Infusion Center Asheville
- Messino Cancer Centers
- Sampson Radiation Oncology
- Southeastern Medical Oncology Center-Clinton
- Southeastern Medical Oncology Center-Goldsboro
- Wayne Memorial Hospital
- Wayne Radiation Oncology
- Hendersonville Hematology and Oncology at Pardee
- Margaret R Pardee Memorial Hospital
- AdventHealth Hendersonville
- Onslow Memorial Hospital
- Southeastern Medical Oncology Center-Jacksonville
- Vidant Oncology-Kinston
- 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
- Cleveland Clinic Akron General
- UHHS-Chagrin Highlands Medical Center
- Strecker Cancer Center-Belpre
- Toledo Clinic Cancer Centers-Bowling Green
- Dayton Physicians LLC-Miami Valley South
- 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
- Mount Carmel East Hospital
- 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
- Dayton Physician LLC-Miami Valley Hospital North
- Miami Valley Hospital North
- Dayton Veterans Affairs Medical Center
- 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
- Armes Family Cancer Center
- Blanchard Valley Hospital
- Orion Cancer Care
- Atrium Medical Center-Middletown Regional Hospital
- Dayton Physicians LLC-Atrium
- Dayton Physicians LLC-Wayne
- Wayne Hospital
- Greater Dayton Cancer Center
- Kettering Medical Center
- Fairfield Medical Center
- Lancaster Radiation Oncology
- Lima Memorial Hospital
- OhioHealth Mansfield Hospital
- Marietta Memorial Hospital
- OhioHealth Marion General Hospital
- Toledo Clinic Cancer Centers-Maumee
- Toledo Radiation Oncology at Northwest Ohio Onocolgy 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
- Dayton Physicians LLC-Signal Point
- Knox Community Hospital
- Licking Memorial Hospital
- Newark Radiation Oncology
- Saint Charles Hospital
- Toledo Clinic Cancer Centers-Oregon
- University Hospitals Parma Medical Center
- Southern Ohio Medical Center
- Dayton Physicians LLC-Wilson
- Springfield Regional Cancer Center
- Springfield Regional Medical Center
- ProMedica Flower Hospital
- Mercy Hospital of Tiffin
- Saint Vincent Mercy Medical Center
- University of Toledo
- Toledo Community Hospital Oncology Program CCOP
- Mercy Health - Saint Anne Hospital
- Toledo Clinic Cancer Centers-Toledo
- Dayton Physicians LLC - Troy
- Upper Valley Medical Center
- University Hospitals Sharon Health Center
- Fulton County Health Center
- University of Cincinnati Cancer Center-West Chester
- Saint Ann's Hospital
- UH Seidman Cancer Center at Saint John Medical Center
- Wright-Patterson Medical Center
- Genesis Healthcare System Cancer Care Center
- Cancer Centers of Southwest Oklahoma Research
- University of Oklahoma Health Sciences Center
- 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
- 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
- UPMC Hillman Cancer Center Erie
- UPMC Cancer Centers - Arnold Palmer Pavilion
- Geisinger Medical Center-Cancer Center Hazleton
- Penn State Milton S Hershey Medical Center
- UPMC-Johnstown/John P. Murtha Regional Cancer Center
- Lancaster General Hospital
- Geisinger Medical Oncology-Lewisburg
- Lewistown Hospital
- UPMC Cancer Center at UPMC McKeesport
- Riddle Memorial Hospital
- UPMC Hillman Cancer Center in Coraopolis
- Paoli Memorial Hospital
- Drexel University School of Medicine
- University of Pennsylvania/Abramson Cancer Center
- Thomas Jefferson University 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
- Pottstown Hospital
- 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
- UPMC Washington Hospital Radiation Oncology
- Reading Hospital
- Geisinger Wyoming Valley/Henry Cancer Center
- UPMC Susquehanna
- Lankenau Medical Center
- Prisma Health Cancer Institute - Spartanburg
- Prisma Health Cancer Institute - Easley
- 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
- Prisma Health Cancer Institute - Seneca
- Spartanburg Medical Center
- MGC Hematology Oncology-Union
- Rapid City Regional Hospital
- Sanford Cancer Center Oncology Clinic
- Avera Cancer Institute
- Sanford USD Medical Center - Sioux Falls
- Bristol Regional Medical Center
- Memorial Hospital
- Pulmonary Medicine Center of Chattanooga-Hixson
- Wellmont Medical Associates Oncology and Hematology-Johnson City
- Ballad Health Cancer Care - Kingsport
- Wellmont Holston Valley Hospital and Medical Center
- Meharry Medical College
- Memorial GYN Plus
- The Don and Sybil Harrington Cancer Center
- Parkland Memorial Hospital
- UT Southwestern/Simmons Cancer Center-Dallas
- Covenant Medical Center-Lakeside
- University Hospital
- University of Texas Health Science Center at San Antonio
- Central Vermont Medical Center/National Life Cancer Treatment
- University of Vermont Medical Center
- University of Vermont and State Agricultural College
- Danville Regional Medical Center
- Fredericksburg Oncology Inc
- Hematology Oncology Associates of Fredericksburg Inc
- Centra Lynchburg Hematology-Oncology Clinic Inc
- Sovah Health Martinsville
- Southwest VA Regional Cancer Center
- Virginia Cancer Institute
- Virginia Commonwealth University/Massey Cancer Center
- VCU Community Memorial Health Center
- Providence Regional Cancer System-Aberdeen
- Cancer Care Center at Island Hospital
- MultiCare Auburn Medical Center
- Virginia Mason Bainbridge Island Medical Center
- Overlake Medical Center
- 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
- 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
- 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
- Peninsula Cancer Center
- MultiCare Good Samaritan Hospital
- Tacoma/Valley Radiation Oncology Centers-Puyallup
- Virginia Mason Medical Center
- Minor and James Medical PLLC
- Pacific Gynecology Specialists
- Swedish Medical Center-Ballard Campus
- FHCC South Lake Union
- Fred Hutchinson Cancer Research Center
- Kaiser Permanente Washington
- Swedish Medical Center-First Hill
- University of Washington Medical Center - Montlake
- 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
- Tacoma/Valley Radiation Oncology Centers-Jackson Hall
- Franciscan Research Center-Northwest Medical Plaza
- MultiCare Tacoma General Hospital
- Northwest Medical Specialties PLLC
- Northwest NCI Community Oncology Research Program
- 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
- United Hospital 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
- Mercyhealth Hospital and Cancer Center - Janesville
- Aurora Cancer Care-Kenosha South
- Gundersen Lutheran Medical Center
- Marshfield Clinic - Ladysmith Center
- Holy Family Memorial Hospital
- Aurora Bay Area Medical Group-Marinette
- 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
Arms of the Study
Arm 1
Arm 2
Experimental
Active Comparator
Arm A (ibrutinib, rituximab)
Arm B (rituximab, fludarabine phosphate, cyclophosphamide)
Patients receive ibrutinib PO QD on days 1-28. Beginning cycle 2, patients also receive rituximab IV over 4 hours on days 1 and 2 of cycle 2, and day 1 of cycles 3-7. Treatment repeats every 28 days for 7 cycles in the absence of unacceptable toxicity. In the absence of disease progression, patients may continue ibrutinib PO QD.
Patients receive rituximab IV over 4 hours on days 1 and 2 of cycle 1, and day 1 of cycles 2-6. Patients also receive fludarabine phosphate IV over 30 minutes and cyclophosphamide IV over 30 minutes on days 1-3. Treatment repeats every 28 days for 6 cycles in the absence of unacceptable toxicity.