Ibrutinib and Rituximab Compared With Fludarabine Phosphate, Cyclophosphamide, and Rituximab in Treating Patients With Untreated Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

Anemia Clinical Trial

Official title:

A Randomized Phase III Study of Ibrutinib (PCI-32765)-Based Therapy vs Standard Fludarabine, Cyclophosphamide, and Rituximab (FCR) Chemoimmunotherapy in Untreated Younger Patients With Chronic Lymphocytic Leukemia (CLL)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02048813
• Other study ID #: NCI-2014-00118
• Secondary ID: NCI-2014-00118E1
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: February 20, 2014
• Est. completion date: December 31, 2024

Study information

• Verified date: February 2024
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This phase III trial studies ibrutinib and rituximab to see how well they work compared to fludarabine phosphate, cyclophosphamide, and rituximab in treating patients with untreated chronic lymphocytic leukemia or small lymphocytic lymphoma. Ibrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Chemotherapy drugs, such as fludarabine phosphate and cyclophosphamide, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Rituximab is a monoclonal antibody. It binds to a protein called CD20, which is found on B cells (a type of white blood cell) and some types of cancer cells. This may help the immune system kill cancer cells. It is not yet known whether fludarabine phosphate, cyclophosphamide, and rituximab may work better than ibrutinib and rituximab in treating patients with untreated chronic lymphocytic leukemia or small lymphocytic lymphoma.

Description:

PRIMARY OBJECTIVE: I. To evaluate the ability of ibrutinib-based induction therapy to prolong progression free survival (PFS) compared to standard fludarabine phosphate, cyclophosphamide, and rituximab (FCR) chemoimmunotherapy for younger patients with chronic lymphocytic leukemia (CLL). SECONDARY OBJECTIVES: I. Evaluate overall survival (OS) of patients based on treatment arm. II. Monitor and assess toxicity of treatment with ibrutinib-based induction relative to standard FCR chemotherapy. III. To compare quality of life (QOL) in CLL patients during the first 6 months of treatment among patients receiving ibrutinib-based induction therapy relative to standard FCR chemoimmunotherapy. IV. To compare QOL over the long-term in CLL patients receiving continuous therapy using ibrutinib to that of CLL patients who completed FCR therapy. V. Determine the effect of pretreatment clinical and biological characteristics (e.g. disease stage, immunoglobulin heavy chain variable region gene [IGHV] mutation status, fluorescent in situ hybridization [FISH]) on clinical outcomes (e.g. complete response, PFS) of the different arms. VI. Determine if the minimal residual disease (MRD) status as assessed by flow cytometry at different time points during and after treatment is an effective surrogate marker for prolonged PFS and overall survival. VII. Compare the genetic abnormalities and dynamics of intra-clonal architecture of CLL patients before and after treatment with chemoimmunotherapy (CIT) and non-CIT approaches and explore relationships with treatment resistance. VIII. Explore the effects of FCR and ibrutinib-based therapy on T-cell immune function. IX. Conduct confirmatory validation genotyping of single nucleotide polymorphisms (SNPs) associated with the efficacy and toxicity of fludarabine-based therapy as in a prior Eastern Cooperative Oncology Group (ECOG) genome-wide association study (GWAS) analysis in the E2997 trial. X. Evaluate the ability of prognostic model that incorporates clinical and biologic characters to predict a response to therapy and clinical outcome (PFS, OS). XI. Evaluate signaling networks downstream of the B-cell receptor in patients receiving ibrutinib-based therapy. XII. Collect relapse samples to study mechanisms of resistance to both FCR and ibrutinib-based therapy. OUTLINE: Patients are randomized to 1 of 2 treatment arms. ARM A: Patients receive ibrutinib orally (PO) once daily (QD) on days 1-28. Beginning cycle 2, patients also receive rituximab intravenously (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. ARM B: 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. After completion of study treatment, patients are followed up for 10 years.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 529
• Est. completion date: December 31, 2024
• Est. primary completion date: October 24, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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)

Related Conditions & MeSH terms

• Anemia
• Chronic Lymphocytic Leukemia
• Leukemia
• Leukemia, Lymphocytic, Chronic, B-Cell
• Leukemia, Lymphoid
• Lymphoma
• Small Lymphocytic Lymphoma

Intervention

Drug:
• Cyclophosphamide
Given IV
• Fludarabine Phosphate
Given IV
• Ibrutinib
Given PO

Other:
• Laboratory Biomarker Analysis
Correlative studies
• Pharmacogenomic Study
Correlative studies
• Quality-of-Life Assessment
Ancillary studies

Biological:
• Rituximab
Given IV

Locations

Country	Name	City	State
United States	Providence Regional Cancer System-Aberdeen	Aberdeen	Washington
United States	Bixby Medical Center	Adrian	Michigan
United States	Hickman Cancer Center	Adrian	Michigan
United States	Cleveland Clinic Akron General	Akron	Ohio
United States	New York Oncology Hematology PC - Albany Medical Center	Albany	New York
United States	Phoebe Putney Memorial Hospital	Albany	Georgia
United States	University of New Mexico Cancer Center	Albuquerque	New Mexico
United States	Lehigh Valley Hospital-Cedar Crest	Allentown	Pennsylvania
United States	The Don and Sybil Harrington Cancer Center	Amarillo	Texas
United States	Mary Greeley Medical Center	Ames	Iowa
United States	McFarland Clinic - Ames	Ames	Iowa
United States	Community Hospital of Anaconda	Anaconda	Montana
United States	Cancer Care Center at Island Hospital	Anacortes	Washington
United States	Kaiser Permanente-Anaheim	Anaheim	California
United States	Alaska Breast Care and Surgery LLC	Anchorage	Alaska
United States	Alaska Oncology and Hematology LLC	Anchorage	Alaska
United States	Alaska Regional Hospital	Anchorage	Alaska
United States	Alaska Women's Cancer Care	Anchorage	Alaska
United States	Anchorage Associates in Radiation Medicine	Anchorage	Alaska
United States	Anchorage Oncology Centre	Anchorage	Alaska
United States	Anchorage Radiation Therapy Center	Anchorage	Alaska
United States	Katmai Oncology Group	Anchorage	Alaska
United States	Providence Alaska Medical Center	Anchorage	Alaska
United States	Ascension Saint Vincent Anderson	Anderson	Indiana
United States	Michigan Cancer Research Consortium NCORP	Ann Arbor	Michigan
United States	Trinity Health Saint Joseph Mercy Hospital Ann Arbor	Ann Arbor	Michigan
United States	Langlade Hospital and Cancer Center	Antigo	Wisconsin
United States	Kaiser Permanente-Deer Valley Medical Center	Antioch	California
United States	PCR Oncology	Arroyo Grande	California
United States	AdventHealth Infusion Center Asheville	Asheville	North Carolina
United States	Messino Cancer Centers	Asheville	North Carolina
United States	Mission Hospital	Asheville	North Carolina
United States	Emory University Hospital/Winship Cancer Institute	Atlanta	Georgia
United States	Hematology Oncology Associates of Central New York-Auburn	Auburn	New York
United States	MultiCare Auburn Medical Center	Auburn	Washington
United States	Sutter Auburn Faith Hospital	Auburn	California
United States	Sutter Cancer Centers Radiation Oncology Services-Auburn	Auburn	California
United States	Harold Alfond Center for Cancer Care	Augusta	Maine
United States	Rocky Mountain Cancer Centers-Aurora	Aurora	Colorado
United States	Rush - Copley Medical Center	Aurora	Illinois
United States	The Medical Center of Aurora	Aurora	Colorado
United States	Virginia Mason Bainbridge Island Medical Center	Bainbridge Island	Washington
United States	Kaiser Permanente-Baldwin Park	Baldwin Park	California
United States	Saint Agnes Hospital	Baltimore	Maryland
United States	University of Maryland/Greenebaum Cancer Center	Baltimore	Maryland
United States	Eastern Maine Medical Center	Bangor	Maine
United States	Flaget Memorial Hospital	Bardstown	Kentucky
United States	Ochsner Health Center-Summa	Baton Rouge	Louisiana
United States	UHHS-Chagrin Highlands Medical Center	Beachwood	Ohio
United States	UPMC-Heritage Valley Health System Beaver	Beaver	Pennsylvania
United States	Overlake Medical Center	Bellevue	Washington
United States	Swedish Cancer Institute-Eastside Oncology Hematology	Bellevue	Washington
United States	Kaiser Permanente-Bellflower	Bellflower	California
United States	PeaceHealth Saint Joseph Medical Center	Bellingham	Washington
United States	Strecker Cancer Center-Belpre	Belpre	Ohio
United States	Sanford Joe Lueken Cancer Center	Bemidji	Minnesota
United States	Saint Charles Health System	Bend	Oregon
United States	Alta Bates Summit Medical Center-Herrick Campus	Berkeley	California
United States	Central Vermont Medical Center/National Life Cancer Treatment	Berlin	Vermont
United States	Lehigh Valley Hospital - Muhlenberg	Bethlehem	Pennsylvania
United States	Beverly Hospital	Beverly	Massachusetts
United States	Billings Clinic Cancer Center	Billings	Montana
United States	Montana Cancer Consortium NCORP	Billings	Montana
United States	Saint Vincent Healthcare	Billings	Montana
United States	University of Alabama at Birmingham Cancer Center	Birmingham	Alabama
United States	Sanford Bismarck Medical Center	Bismarck	North Dakota
United States	Illinois CancerCare-Bloomington	Bloomington	Illinois
United States	OSF Saint Joseph Medical Center	Bloomington	Illinois
United States	Prisma Health Cancer Institute - Spartanburg	Boiling Springs	South Carolina
United States	Saint Alphonsus Cancer Care Center-Boise	Boise	Idaho
United States	Saint Luke's Cancer Institute - Boise	Boise	Idaho
United States	Central Care Cancer Center - Bolivar	Bolivar	Missouri
United States	Parkland Health Center-Bonne Terre	Bonne Terre	Missouri
United States	McFarland Clinic - Boone	Boone	Iowa
United States	Eastern Cooperative Oncology Group	Boston	Massachusetts
United States	Tufts Medical Center	Boston	Massachusetts
United States	Boulder Community Hospital	Boulder	Colorado
United States	Rocky Mountain Cancer Centers-Boulder	Boulder	Colorado
United States	Toledo Clinic Cancer Centers-Bowling Green	Bowling Green	Ohio
United States	Bozeman Health Deaconess Hospital	Bozeman	Montana
United States	Essentia Health Saint Joseph's Medical Center	Brainerd	Minnesota
United States	Cox Cancer Center Branson	Branson	Missouri
United States	Harrison HealthPartners Hematology and Oncology-Bremerton	Bremerton	Washington
United States	Lafayette Family Cancer Center-EMMC	Brewer	Maine
United States	United Hospital Center	Bridgeport	West Virginia
United States	Bristol Regional Medical Center	Bristol	Tennessee
United States	Henry Ford Cancer Institute-Downriver	Brownstown	Michigan
United States	Bryn Mawr Hospital	Bryn Mawr	Pennsylvania
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	Providence Saint Joseph Medical Center/Disney Family Cancer Center	Burbank	California
United States	Highline Medical Center-Main Campus	Burien	Washington
United States	Mills-Peninsula Medical Center	Burlingame	California
United States	Aurora Cancer Care-Southern Lakes VLCC	Burlington	Wisconsin
United States	Lahey Hospital and Medical Center	Burlington	Massachusetts
United States	University of Vermont and State Agricultural College	Burlington	Vermont
United States	University of Vermont Medical Center	Burlington	Vermont
United States	Fairview Ridges Hospital	Burnsville	Minnesota
United States	Saint James Community Hospital and Cancer Treatment Center	Butte	Montana
United States	Sutter Cancer Centers Radiation Oncology Services-Cameron Park	Cameron Park	California
United States	Illinois CancerCare-Canton	Canton	Illinois
United States	Saint Francis Medical Center	Cape Girardeau	Missouri
United States	Southeast Cancer Center	Cape Girardeau	Missouri
United States	Memorial Hospital of Carbondale	Carbondale	Illinois
United States	Illinois CancerCare-Carthage	Carthage	Illinois
United States	Rocky Mountain Oncology	Casper	Wyoming
United States	Eden Hospital Medical Center	Castro Valley	California
United States	Dayton Physicians LLC-Miami Valley South	Centerville	Ohio
United States	Miami Valley Hospital South	Centerville	Ohio
United States	Centralia Oncology Clinic	Centralia	Illinois
United States	Providence Regional Cancer System-Centralia	Centralia	Washington
United States	Christiana Care Health System-Concord Health Center	Chadds Ford	Pennsylvania
United States	Cancer Center of Kansas - Chanute	Chanute	Kansas
United States	Geauga Hospital	Chardon	Ohio
United States	Memorial Hospital	Chattanooga	Tennessee
United States	Cheyenne Regional Medical Center-West	Cheyenne	Wyoming
United States	Northwestern University	Chicago	Illinois
United States	University of Chicago Comprehensive Cancer Center	Chicago	Illinois
United States	Adventist Health Cancer Care Center Chico	Chico	California
United States	Adena Regional Medical Center	Chillicothe	Ohio
United States	Marshfield Clinic-Chippewa Center	Chippewa Falls	Wisconsin
United States	Bethesda North Hospital	Cincinnati	Ohio
United States	Good Samaritan Hospital - Cincinnati	Cincinnati	Ohio
United States	Oncology Hematology Care Inc-Anderson	Cincinnati	Ohio
United States	Oncology Hematology Care Inc-Blue Ash	Cincinnati	Ohio
United States	Oncology Hematology Care Inc-Eden Park	Cincinnati	Ohio
United States	Oncology Hematology Care Inc-Kenwood	Cincinnati	Ohio
United States	Oncology Hematology Care Inc-Mercy West	Cincinnati	Ohio
United States	TriHealth Cancer Institute-Anderson	Cincinnati	Ohio
United States	TriHealth Cancer Institute-Westside	Cincinnati	Ohio
United States	University of Cincinnati Cancer Center-UC Medical Center	Cincinnati	Ohio
United States	Clackamas Radiation Oncology Center	Clackamas	Oregon
United States	Providence Cancer Institute Clackamas Clinic	Clackamas	Oregon
United States	Case Western Reserve University	Cleveland	Ohio
United States	MetroHealth Medical Center	Cleveland	Ohio
United States	Sampson Radiation Oncology	Clinton	North Carolina
United States	Southeastern Medical Oncology Center-Clinton	Clinton	North Carolina
United States	Henry Ford Macomb Hospital-Clinton Township	Clinton Township	Michigan
United States	Mercy Cancer Center-West Lakes	Clive	Iowa
United States	Mission Cancer and Blood - West Des Moines	Clive	Iowa
United States	Big Horn Basin Cancer Center	Cody	Wyoming
United States	Billings Clinic-Cody	Cody	Wyoming
United States	Kootenai Health - Coeur d'Alene	Coeur d'Alene	Idaho
United States	Penrose-Saint Francis Healthcare	Colorado Springs	Colorado
United States	Rocky Mountain Cancer Centers-Penrose	Colorado Springs	Colorado
United States	Columbus NCI Community Oncology Research Program	Columbus	Ohio
United States	Columbus Oncology and Hematology Associates Inc	Columbus	Ohio
United States	Doctors Hospital	Columbus	Ohio
United States	Grant Medical Center	Columbus	Ohio
United States	John B Amos Cancer Center	Columbus	Georgia
United States	Mount Carmel East Hospital	Columbus	Ohio
United States	Mount Carmel Health Center West	Columbus	Ohio
United States	Riverside Methodist Hospital	Columbus	Ohio
United States	The Mark H Zangmeister Center	Columbus	Ohio
United States	John Muir Medical Center-Concord	Concord	California
United States	Mercy Hospital	Coon Rapids	Minnesota
United States	Bay Area Hospital	Coos Bay	Oregon
United States	Commonwealth Cancer Center-Corbin	Corbin	Kentucky
United States	Alegent Health Mercy Hospital	Council Bluffs	Iowa
United States	Greater Regional Medical Center	Creston	Iowa
United States	Oncology Hematology Care Inc-Crestview	Crestview Hills	Kentucky
United States	Siteman Cancer Center at West County Hospital	Creve Coeur	Missouri
United States	Parkland Memorial Hospital	Dallas	Texas
United States	UT Southwestern/Simmons Cancer Center-Dallas	Dallas	Texas
United States	Carle at The Riverfront	Danville	Illinois
United States	Danville Regional Medical Center	Danville	Virginia
United States	Geisinger Medical Center	Danville	Pennsylvania
United States	Sutter Davis Hospital	Davis	California
United States	Dayton NCI Community Oncology Research Program	Dayton	Ohio
United States	Dayton Physician LLC - Englewood	Dayton	Ohio
United States	Dayton Veterans Affairs Medical Center	Dayton	Ohio
United States	Good Samaritan Hospital - Dayton	Dayton	Ohio
United States	Miami Valley Hospital	Dayton	Ohio
United States	Miami Valley Hospital North	Dayton	Ohio
United States	Beaumont Hospital - Dearborn	Dearborn	Michigan
United States	Henry Ford Medical Center-Fairlane	Dearborn	Michigan
United States	Cancer Care Specialists of Illinois - Decatur	Decatur	Illinois
United States	Decatur Memorial Hospital	Decatur	Illinois
United States	Delaware Health Center-Grady Cancer Center	Delaware	Ohio
United States	Delaware Radiation Oncology	Delaware	Ohio
United States	Grady Memorial Hospital	Delaware	Ohio
United States	Colorado Blood Cancer Institute	Denver	Colorado
United States	Denver Health Medical Center	Denver	Colorado
United States	Kaiser Permanente-Franklin	Denver	Colorado
United States	National Jewish Health-Main Campus	Denver	Colorado
United States	Porter Adventist Hospital	Denver	Colorado
United States	Presbyterian - Saint Lukes Medical Center - Health One	Denver	Colorado
United States	Rocky Mountain Cancer Centers-Midtown	Denver	Colorado
United States	Rocky Mountain Cancer Centers-Rose	Denver	Colorado
United States	Rose Medical Center	Denver	Colorado
United States	SCL Health Saint Joseph Hospital	Denver	Colorado
United States	Western States Cancer Research NCORP	Denver	Colorado
United States	Smilow Cancer Hospital-Derby Care Center	Derby	Connecticut
United States	Mercy Medical Center - Des Moines	Des Moines	Iowa
United States	Mission Cancer and Blood - Laurel	Des Moines	Iowa
United States	Ascension Saint John Hospital	Detroit	Michigan
United States	Henry Ford Hospital	Detroit	Michigan
United States	Wayne State University/Karmanos Cancer Institute	Detroit	Michigan
United States	Cancer Center of Kansas - Dodge City	Dodge City	Kansas
United States	Wentworth-Douglass Hospital	Dover	New Hampshire
United States	Essentia Health Cancer Center	Duluth	Minnesota
United States	Essentia Health Saint Mary's Medical Center	Duluth	Minnesota
United States	Miller-Dwan Hospital	Duluth	Minnesota
United States	Mercy Medical Center	Durango	Colorado
United States	Southwest Oncology PC	Durango	Colorado
United States	Prisma Health Cancer Institute - Easley	Easley	South Carolina
United States	Veterans Adminstration New Jersey Health Care System	East Orange	New Jersey
United States	HSHS Sacred Heart Hospital	Eau Claire	Wisconsin
United States	Marshfield Clinic Cancer Center at Sacred Heart	Eau Claire	Wisconsin
United States	Fairview Southdale Hospital	Edina	Minnesota
United States	Swedish Cancer Institute-Edmonds	Edmonds	Washington
United States	Carle Physician Group-Effingham	Effingham	Illinois
United States	Crossroads Cancer Center	Effingham	Illinois
United States	Cancer Center of Kansas - El Dorado	El Dorado	Kansas
United States	Ascension Alexian Brothers - Elk Grove Village	Elk Grove Village	Illinois
United States	Mercy Cancer Center-Elyria	Elyria	Ohio
United States	Mountain Blue Cancer Care Center - Swedish	Englewood	Colorado
United States	Swedish Medical Center	Englewood	Colorado
United States	Saint Elizabeth Hospital	Enumclaw	Washington
United States	UPMC Hillman Cancer Center Erie	Erie	Pennsylvania
United States	OSF Saint Francis Hospital and Medical Group	Escanaba	Michigan
United States	Illinois CancerCare-Eureka	Eureka	Illinois
United States	NorthShore University HealthSystem-Evanston Hospital	Evanston	Illinois
United States	Providence Regional Cancer Partnership	Everett	Washington
United States	Fairbanks Memorial Hospital	Fairbanks	Alaska
United States	Oncology Hematology Care Inc-Healthplex	Fairfield	Ohio
United States	Smilow Cancer Hospital Care Center-Fairfield	Fairfield	Connecticut
United States	Essentia Health Cancer Center-South University Clinic	Fargo	North Dakota
United States	Sanford Broadway Medical Center	Fargo	North Dakota
United States	Sanford Clinic North-Fargo	Fargo	North Dakota
United States	Sanford Roger Maris Cancer Center	Fargo	North Dakota
United States	Beaumont Hospital - Farmington Hills	Farmington Hills	Michigan
United States	Weisberg Cancer Treatment Center	Farmington Hills	Michigan
United States	Saint Francis Hospital	Federal Way	Washington
United States	Virginia Mason Federal Way Medical Center	Federal Way	Washington
United States	Lake Region Healthcare Corporation-Cancer Care	Fergus Falls	Minnesota
United States	Armes Family Cancer Center	Findlay	Ohio
United States	Blanchard Valley Hospital	Findlay	Ohio
United States	Orion Cancer Care	Findlay	Ohio
United States	Genesys Hurley Cancer Institute	Flint	Michigan
United States	Hurley Medical Center	Flint	Michigan
United States	Aurora Health Center-Fond du Lac	Fond Du Lac	Wisconsin
United States	Kaiser Permanente-Fontana	Fontana	California
United States	McFarland Clinic - Trinity Cancer Center	Fort Dodge	Iowa
United States	Cancer Center of Kansas - Fort Scott	Fort Scott	Kansas
United States	Atrium Medical Center-Middletown Regional Hospital	Franklin	Ohio
United States	Dayton Physicians LLC-Atrium	Franklin	Ohio
United States	Fredericksburg Oncology Inc	Fredericksburg	Virginia
United States	Hematology Oncology Associates of Fredericksburg Inc	Fredericksburg	Virginia
United States	Kaiser Permanente-Fremont	Fremont	California
United States	Kaiser Permanente-Fresno	Fresno	California
United States	Unity Hospital	Fridley	Minnesota
United States	Saint Luke's Cancer Institute - Fruitland	Fruitland	Idaho
United States	Gibbs Cancer Center-Gaffney	Gaffney	South Carolina
United States	Illinois CancerCare-Galesburg	Galesburg	Illinois
United States	Western Illinois Cancer Treatment Center	Galesburg	Illinois
United States	Northwestern Medicine Cancer Center Delnor	Geneva	Illinois
United States	Aurora Health Care Germantown Health Center	Germantown	Wisconsin
United States	MultiCare Gig Harbor Medical Park	Gig Harbor	Washington
United States	Tacoma/Valley Radiation Oncology Centers-Gig Harbor	Gig Harbor	Washington
United States	Glens Falls Hospital	Glens Falls	New York
United States	NorthShore University HealthSystem-Glenbrook Hospital	Glenview	Illinois
United States	Addison Gilbert Hospital	Gloucester	Massachusetts
United States	Mountain Blue Cancer Care Center	Golden	Colorado
United States	National Jewish Health-Western Hematology Oncology	Golden	Colorado
United States	Southeastern Medical Oncology Center-Goldsboro	Goldsboro	North Carolina
United States	Wayne Memorial Hospital	Goldsboro	North Carolina
United States	Wayne Radiation Oncology	Goldsboro	North Carolina
United States	Aurora Cancer Care-Grafton	Grafton	Wisconsin
United States	Nebraska Cancer Specialists/Oncology Hematology West PC	Grand Island	Nebraska
United States	Benefis Sletten Cancer Institute	Great Falls	Montana
United States	Great Falls Clinic	Great Falls	Montana
United States	Banner North Colorado Medical Center	Greeley	Colorado
United States	Aurora BayCare Medical Center	Green Bay	Wisconsin
United States	Bellin Memorial Hospital	Green Bay	Wisconsin
United States	Green Bay Oncology at Saint Vincent Hospital	Green Bay	Wisconsin
United States	Green Bay Oncology Limited at Saint Mary's Hospital	Green Bay	Wisconsin
United States	Saint Vincent Hospital Cancer Center at Saint Mary's	Green Bay	Wisconsin
United States	Saint Vincent Hospital Cancer Center Green Bay	Green Bay	Wisconsin
United States	Marin Cancer Care Inc	Greenbrae	California
United States	Marin General Hospital	Greenbrae	California
United States	UPMC Cancer Centers - Arnold Palmer Pavilion	Greensburg	Pennsylvania
United States	Dayton Physicians LLC-Wayne	Greenville	Ohio
United States	Greenville Health System Cancer Institute-Andrews	Greenville	South Carolina
United States	Prisma Health Cancer Institute - Butternut	Greenville	South Carolina
United States	Prisma Health Cancer Institute - Eastside	Greenville	South Carolina
United States	Prisma Health Cancer Institute - Faris	Greenville	South Carolina
United States	Prisma Health Greenville Memorial Hospital	Greenville	South Carolina
United States	Saint Francis Cancer Center	Greenville	South Carolina
United States	Saint Francis Hospital	Greenville	South Carolina
United States	Wayne Hospital	Greenville	Ohio
United States	Rocky Mountain Cancer Centers-Greenwood Village	Greenwood Village	Colorado
United States	Gibbs Cancer Center-Pelham	Greer	South Carolina
United States	Prisma Health Cancer Institute - Greer	Greer	South Carolina
United States	William Beaumont Hospital-Grosse Pointe	Grosse Pointe	Michigan
United States	Kaiser Permanente - Harbor City	Harbor City	California
United States	Smilow Cancer Hospital Care Center at Saint Francis	Hartford	Connecticut
United States	Geisinger Medical Center-Cancer Center Hazleton	Hazleton	Pennsylvania
United States	Saint Peter's Community Hospital	Helena	Montana
United States	Cancer and Blood Specialists-Henderson	Henderson	Nevada
United States	Comprehensive Cancer Centers of Nevada - Henderson	Henderson	Nevada
United States	Comprehensive Cancer Centers of Nevada-Southeast Henderson	Henderson	Nevada
United States	GenesisCare USA - Henderson	Henderson	Nevada
United States	Las Vegas Cancer Center-Henderson	Henderson	Nevada
United States	AdventHealth Hendersonville	Hendersonville	North Carolina
United States	Hendersonville Hematology and Oncology at Pardee	Hendersonville	North Carolina
United States	Margaret R Pardee Memorial Hospital	Hendersonville	North Carolina
United States	Penn State Milton S Hershey Medical Center	Hershey	Pennsylvania
United States	Hematology Oncology Associates of Illinois-Highland Park	Highland Park	Illinois
United States	NorthShore University HealthSystem-Highland Park Hospital	Highland Park	Illinois
United States	Pulmonary Medicine Center of Chattanooga-Hixson	Hixson	Tennessee
United States	Kaiser Permanente Moanalua Medical Center	Honolulu	Hawaii
United States	CHI Saint Vincent Cancer Center Hot Springs	Hot Springs	Arkansas
United States	Hutchinson Area Health Care	Hutchinson	Minnesota
United States	Cancer Center of Kansas-Independence	Independence	Kansas
United States	Centerpoint Medical Center LLC	Independence	Missouri
United States	Green Bay Oncology - Iron Mountain	Iron Mountain	Michigan
United States	Kaiser Permanente-Irvine	Irvine	California
United States	Swedish Cancer Institute-Issaquah	Issaquah	Washington
United States	Allegiance Health	Jackson	Michigan
United States	Baptist MD Anderson Cancer Center	Jacksonville	Florida
United States	Onslow Memorial Hospital	Jacksonville	North Carolina
United States	Southeastern Medical Oncology Center-Jacksonville	Jacksonville	North Carolina
United States	Mercyhealth Hospital and Cancer Center - Janesville	Janesville	Wisconsin
United States	McFarland Clinic - Jefferson	Jefferson	Iowa
United States	MU Health Care Goldschmidt Cancer Center	Jefferson City	Missouri
United States	Wellmont Medical Associates Oncology and Hematology-Johnson City	Johnson City	Tennessee
United States	UPMC-Johnstown/John P. Murtha Regional Cancer Center	Johnstown	Pennsylvania
United States	Duly Health and Care Joliet	Joliet	Illinois
United States	NEA Baptist Memorial Hospital and Fowler Family Cancer Center - Jonesboro	Jonesboro	Arkansas
United States	Freeman Health System	Joplin	Missouri
United States	Mercy Hospital Joplin	Joplin	Missouri
United States	West Michigan Cancer Center	Kalamazoo	Michigan
United States	Kalispell Regional Medical Center	Kalispell	Montana
United States	Presence Saint Mary's Hospital	Kankakee	Illinois
United States	Heartland Hematology and Oncology Associates Incorporated	Kansas City	Missouri
United States	Research Medical Center	Kansas City	Missouri
United States	Saint Luke's Hospital of Kansas City	Kansas City	Missouri
United States	CHI Health Good Samaritan	Kearney	Nebraska
United States	Heartland Hematology and Oncology	Kearney	Nebraska
United States	Ochsner Medical Center Kenner	Kenner	Louisiana
United States	Northwest Cancer Clinic	Kennewick	Washington
United States	Aurora Cancer Care-Kenosha South	Kenosha	Wisconsin
United States	Greater Dayton Cancer Center	Kettering	Ohio
United States	Kettering Medical Center	Kettering	Ohio
United States	Illinois CancerCare-Kewanee Clinic	Kewanee	Illinois
United States	Cancer Center of Kansas-Kingman	Kingman	Kansas
United States	Ballad Health Cancer Care - Kingsport	Kingsport	Tennessee
United States	Wellmont Holston Valley Hospital and Medical Center	Kingsport	Tennessee
United States	ECU Health Oncology Kinston	Kinston	North Carolina
United States	Gundersen Lutheran Medical Center	La Crosse	Wisconsin
United States	Providence Regional Cancer System-Lacey	Lacey	Washington
United States	Marshfield Medical Center - Ladysmith	Ladysmith	Wisconsin
United States	Kaiser Permanente-Rock Creek	Lafayette	Colorado
United States	Northwell Health/Center for Advanced Medicine	Lake Success	New York
United States	Lakeland Regional Health Hollis Cancer Center	Lakeland	Florida
United States	Rocky Mountain Cancer Centers-Lakewood	Lakewood	Colorado
United States	Saint Anthony Hospital	Lakewood	Colorado
United States	Saint Clare Hospital	Lakewood	Washington
United States	Fairfield Medical Center	Lancaster	Ohio
United States	Lancaster General Hospital	Lancaster	Pennsylvania
United States	Lancaster Radiation Oncology	Lancaster	Ohio
United States	University of Michigan Health - Sparrow Lansing	Lansing	Michigan
United States	Cancer and Blood Specialists-Shadow	Las Vegas	Nevada
United States	Cancer and Blood Specialists-Tenaya	Las Vegas	Nevada
United States	Cancer Therapy and Integrative Medicine	Las Vegas	Nevada
United States	Comprehensive Cancer Centers of Nevada	Las Vegas	Nevada
United States	Comprehensive Cancer Centers of Nevada - Central Valley	Las Vegas	Nevada
United States	Comprehensive Cancer Centers of Nevada - Northwest	Las Vegas	Nevada
United States	Comprehensive Cancer Centers of Nevada-Summerlin	Las Vegas	Nevada
United States	GenesisCare USA - Fort Apache	Las Vegas	Nevada
United States	GenesisCare USA - Las Vegas	Las Vegas	Nevada
United States	GenesisCare USA - Vegas Tenaya	Las Vegas	Nevada
United States	HealthCare Partners Medical Group Oncology/Hematology-Centennial Hills	Las Vegas	Nevada
United States	HealthCare Partners Medical Group Oncology/Hematology-Maryland Parkway	Las Vegas	Nevada
United States	HealthCare Partners Medical Group Oncology/Hematology-San Martin	Las Vegas	Nevada
United States	HealthCare Partners Medical Group Oncology/Hematology-Tenaya	Las Vegas	Nevada
United States	Las Vegas Cancer Center-Medical Center	Las Vegas	Nevada
United States	Nevada Cancer Research Foundation NCORP	Las Vegas	Nevada
United States	OptumCare Cancer Care at Fort Apache	Las Vegas	Nevada
United States	Radiation Oncology Centers of Nevada Central	Las Vegas	Nevada
United States	Radiation Oncology Centers of Nevada Southeast	Las Vegas	Nevada
United States	Summerlin Hospital Medical Center	Las Vegas	Nevada
United States	Lawrence Memorial Hospital	Lawrence	Kansas
United States	Cancer Centers of Southwest Oklahoma Research	Lawton	Oklahoma
United States	Saint Luke's East - Lee's Summit	Lee's Summit	Missouri
United States	Kansas Institute of Medicine Cancer and Blood Center	Lenexa	Kansas
United States	Minimally Invasive Surgery Hospital	Lenexa	Kansas
United States	Beebe Medical Center	Lewes	Delaware
United States	Geisinger Medical Oncology-Lewisburg	Lewisburg	Pennsylvania
United States	Lewistown Hospital	Lewistown	Pennsylvania
United States	Saint Joseph Hospital East	Lexington	Kentucky
United States	Saint Joseph Radiation Oncology Resource Center	Lexington	Kentucky
United States	Cancer Center of Kansas-Liberal	Liberal	Kansas
United States	Liberty Radiation Oncology Center	Liberty	Missouri
United States	AMG Libertyville - Oncology	Libertyville	Illinois
United States	Lima Memorial Hospital	Lima	Ohio
United States	Cancer Partners of Nebraska	Lincoln	Nebraska
United States	Nebraska Cancer Research Center	Lincoln	Nebraska
United States	Nebraska Hematology and Oncology	Lincoln	Nebraska
United States	Saint Elizabeth Regional Medical Center	Lincoln	Nebraska
United States	University of Arkansas for Medical Sciences	Little Rock	Arkansas
United States	Littleton Adventist Hospital	Littleton	Colorado
United States	Rocky Mountain Cancer Centers-Littleton	Littleton	Colorado
United States	Hematology Oncology Associates of Central New York-Liverpool	Liverpool	New York
United States	Trinity Health Saint Mary Mercy Livonia Hospital	Livonia	Michigan
United States	Kaiser Permanente-Lone Tree	Lone Tree	Colorado
United States	Rocky Mountain Cancer Centers-Sky Ridge	Lone Tree	Colorado
United States	Sky Ridge Medical Center	Lone Tree	Colorado
United States	Longmont United Hospital	Longmont	Colorado
United States	Rocky Mountain Cancer Centers-Longmont	Longmont	Colorado
United States	PeaceHealth Saint John Medical Center	Longview	Washington
United States	Kaiser Permanente Los Angeles Medical Center	Los Angeles	California
United States	Kaiser Permanente West Los Angeles	Los Angeles	California
United States	Jewish Hospital	Louisville	Kentucky
United States	Saints Mary and Elizabeth Hospital	Louisville	Kentucky
United States	UofL Health Medical Center Northeast	Louisville	Kentucky
United States	Banner McKee Medical Center	Loveland	Colorado
United States	Covenant Medical Center-Lakeside	Lubbock	Texas
United States	Centra Alan B Pearson Regional Cancer Center	Lynchburg	Virginia
United States	Virginia Mason Lynnwood Medical Center	Lynnwood	Washington
United States	Illinois CancerCare-Macomb	Macomb	Illinois
United States	Atrium Health Navicent	Macon	Georgia
United States	Central Georgia Gynecologic Oncology	Macon	Georgia
United States	North Shore University Hospital	Manhasset	New York
United States	Holy Family Memorial Hospital	Manitowoc	Wisconsin
United States	OhioHealth Mansfield Hospital	Mansfield	Ohio
United States	Minnesota Oncology Hematology PA-Maplewood	Maplewood	Minnesota
United States	Saint John's Hospital - Healtheast	Maplewood	Minnesota
United States	Marietta Memorial Hospital	Marietta	Ohio
United States	Aurora Bay Area Medical Group-Marinette	Marinette	Wisconsin
United States	OhioHealth Marion General Hospital	Marion	Ohio
United States	McFarland Clinic - Marshalltown	Marshalltown	Iowa
United States	Marshfield Medical Center	Marshfield	Wisconsin
United States	Marshfield Medical Center-Marshfield	Marshfield	Wisconsin
United States	WVUH-Berkely Medical Center	Martinsburg	West Virginia
United States	Sovah Health Martinsville	Martinsville	Virginia
United States	Mercy Medical Center - North Iowa	Mason City	Iowa
United States	Carle Physician Group-Mattoon/Charleston	Mattoon	Illinois
United States	Toledo Clinic Cancer Centers-Maumee	Maumee	Ohio
United States	Toledo Radiation Oncology at Northwest Ohio Onocolgy Center	Maumee	Ohio
United States	UH Seidman Cancer Center at Landerbrook Health Center	Mayfield Heights	Ohio
United States	Loyola University Medical Center	Maywood	Illinois
United States	UPMC Cancer Center at UPMC McKeesport	McKeesport	Pennsylvania
United States	Riddle Memorial Hospital	Media	Pennsylvania
United States	UH Seidman Cancer Center at Lake Health Mentor Campus	Mentor	Ohio
United States	Saint Luke's Cancer Institute - Meridian	Meridian	Idaho
United States	Franciscan Saint Anthony Health-Michigan City	Michigan City	Indiana
United States	Woodland Cancer Care Center	Michigan City	Indiana
United States	UH Seidman Cancer Center at Southwest General Hospital	Middleburg Heights	Ohio
United States	Dayton Physicians LLC-Signal Point	Middletown	Ohio
United States	Garnet Health Medical Center	Middletown	New York
United States	Middlesex Hospital	Middletown	Connecticut
United States	Aurora Cancer Care-Milwaukee	Milwaukee	Wisconsin
United States	Aurora Saint Luke's Medical Center	Milwaukee	Wisconsin
United States	Aurora Sinai Medical Center	Milwaukee	Wisconsin
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Providence Milwaukie Hospital	Milwaukie	Oregon
United States	Abbott-Northwestern Hospital	Minneapolis	Minnesota
United States	Health Partners Inc	Minneapolis	Minnesota
United States	Hennepin County Medical Center	Minneapolis	Minnesota
United States	Marshfield Clinic-Minocqua Center	Minocqua	Wisconsin
United States	Memorial Regional Cancer Center Day Road	Mishawaka	Indiana
United States	Community Medical Center	Missoula	Montana
United States	Saint Patrick Hospital - Community Hospital	Missoula	Montana
United States	Kaiser Permanente-Modesto	Modesto	California
United States	Memorial Medical Center	Modesto	California
United States	Trinity Medical Center	Moline	Illinois
United States	Mercy Memorial Hospital	Monroe	Michigan
United States	Monroe Cancer Center	Monroe	Michigan
United States	Ochsner LSU Health Monroe Medical Center	Monroe	Louisiana
United States	Toledo Clinic Cancer Centers-Monroe	Monroe	Michigan
United States	UPMC Hillman Cancer Center in Coraopolis	Moon	Pennsylvania
United States	West Virginia University Healthcare	Morgantown	West Virginia
United States	Good Samaritan Regional Health Center	Mount Vernon	Illinois
United States	Knox Community Hospital	Mount Vernon	Ohio
United States	Palo Alto Medical Foundation-Camino Division	Mountain View	California
United States	Palo Alto Medical Foundation-Gynecologic Oncology	Mountain View	California
United States	ProHealth D N Greenwald Center	Mukwonago	Wisconsin
United States	Saint Luke's Cancer Institute - Nampa	Nampa	Idaho
United States	Meharry Medical College	Nashville	Tennessee
United States	Smilow Cancer Center/Yale-New Haven Hospital	New Haven	Connecticut
United States	Yale University	New Haven	Connecticut
United States	Long Island Jewish Medical Center	New Hyde Park	New York
United States	UC Comprehensive Cancer Center at Silver Cross	New Lenox	Illinois
United States	Ochsner Medical Center Jefferson	New Orleans	Louisiana
United States	Cancer Center of Western Wisconsin	New Richmond	Wisconsin
United States	New Ulm Medical Center	New Ulm	Minnesota
United States	Christiana Care Health System-Christiana Hospital	Newark	Delaware
United States	Christiana Gynecologic Oncology LLC	Newark	Delaware
United States	Delaware Clinical and Laboratory Physicians PA	Newark	Delaware
United States	Helen F Graham Cancer Center	Newark	Delaware
United States	Licking Memorial Hospital	Newark	Ohio
United States	Medical Oncology Hematology Consultants PA	Newark	Delaware
United States	Newark Beth Israel Medical Center	Newark	New Jersey
United States	Newark Radiation Oncology	Newark	Ohio
United States	Providence Newberg Medical Center	Newberg	Oregon
United States	Cancer Center of Kansas - Newton	Newton	Kansas
United States	Illinois Cancer Specialists-Niles	Niles	Illinois
United States	Faith Regional Health Services Carson Cancer Center	Norfolk	Nebraska
United States	Carle Cancer Institute Normal	Normal	Illinois
United States	Yale-New Haven Hospital North Haven Medical Center	North Haven	Connecticut
United States	Great Plains Health Callahan Cancer Center	North Platte	Nebraska
United States	Southwest VA Regional Cancer Center	Norton	Virginia
United States	Sutter Cancer Research Consortium	Novato	California
United States	Ascension Providence Hospitals - Novi	Novi	Michigan
United States	Henry Ford Medical Center-Columbus	Novi	Michigan
United States	Cancer Care Center of O'Fallon	O'Fallon	Illinois
United States	Advocate Christ Medical Center	Oak Lawn	Illinois
United States	Kaiser Permanente-Oakland	Oakland	California
United States	ProHealth Oconomowoc Memorial Hospital	Oconomowoc	Wisconsin
United States	Saint Vincent Hospital Cancer Center at Oconto Falls	Oconto Falls	Wisconsin
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	Alegent Health Bergan Mercy Medical Center	Omaha	Nebraska
United States	Alegent Health Immanuel Medical Center	Omaha	Nebraska
United States	Alegent Health Lakeside Hospital	Omaha	Nebraska
United States	Creighton University Medical Center	Omaha	Nebraska
United States	Hematology and Oncology Consultants PC	Omaha	Nebraska
United States	Missouri Valley Cancer Consortium	Omaha	Nebraska
United States	Nebraska Cancer Specialists - Omaha	Omaha	Nebraska
United States	Oncology Hematology West PC	Omaha	Nebraska
United States	University of Nebraska Medical Center	Omaha	Nebraska
United States	Memorial GYN Plus	Ooltewah	Tennessee
United States	Smilow Cancer Hospital-Orange Care Center	Orange	Connecticut
United States	UC Irvine Health/Chao Family Comprehensive Cancer Center	Orange	California
United States	Saint Charles Hospital	Oregon	Ohio
United States	Toledo Clinic Cancer Centers-Oregon	Oregon	Ohio
United States	Providence Willamette Falls Medical Center	Oregon City	Oregon
United States	Orlando Health Cancer Institute	Orlando	Florida
United States	Vince Lombardi Cancer Clinic - Oshkosh	Oshkosh	Wisconsin
United States	Illinois CancerCare-Ottawa Clinic	Ottawa	Illinois
United States	Radiation Oncology of Northern Illinois	Ottawa	Illinois
United States	Menorah Medical Center	Overland Park	Kansas
United States	Saint Luke's South Hospital	Overland Park	Kansas
United States	Palo Alto Medical Foundation Health Care	Palo Alto	California
United States	Stanford Cancer Institute Palo Alto	Palo Alto	California
United States	Kaiser Permanente - Panorama City	Panorama City	California
United States	Paoli Memorial Hospital	Paoli	Pennsylvania
United States	Midlands Community Hospital	Papillion	Nebraska
United States	Parker Adventist Hospital	Parker	Colorado
United States	Rocky Mountain Cancer Centers-Parker	Parker	Colorado
United States	Camden Clark Medical Center	Parkersburg	West Virginia
United States	University Hospitals Parma Medical Center	Parma	Ohio
United States	Cancer Center of Kansas - Parsons	Parsons	Kansas
United States	Illinois CancerCare-Pekin	Pekin	Illinois
United States	OSF Saint Francis Radiation Oncology at Pekin	Pekin	Illinois
United States	Illinois CancerCare-Peoria	Peoria	Illinois
United States	Methodist Medical Center of Illinois	Peoria	Illinois
United States	OSF Saint Francis Medical Center	Peoria	Illinois
United States	OSF Saint Francis Radiation Oncology at Peoria Cancer Center	Peoria	Illinois
United States	Illinois CancerCare-Peru	Peru	Illinois
United States	Valley Radiation Oncology	Peru	Illinois
United States	Drexel University School of Medicine	Philadelphia	Pennsylvania
United States	Thomas Jefferson University Hospital	Philadelphia	Pennsylvania
United States	University of Pennsylvania/Abramson Cancer Center	Philadelphia	Pennsylvania
United States	University of Pittsburgh Cancer Institute (UPCI)	Pittsburgh	Pennsylvania
United States	UPMC Jefferson Regional Radiation Oncology	Pittsburgh	Pennsylvania
United States	UPMC-Magee Womens Hospital	Pittsburgh	Pennsylvania
United States	UPMC-Passavant Hospital	Pittsburgh	Pennsylvania
United States	UPMC-Presbyterian Hospital	Pittsburgh	Pennsylvania
United States	UPMC-Saint Clair Hospital Cancer Center	Pittsburgh	Pennsylvania
United States	UPMC-Saint Margaret	Pittsburgh	Pennsylvania
United States	UPMC-Shadyside Hospital	Pittsburgh	Pennsylvania
United States	Trinity Health Saint Joseph Mercy Oakland Hospital	Pontiac	Michigan
United States	Lake Huron Medical Center	Port Huron	Michigan
United States	Jefferson Healthcare	Port Townsend	Washington
United States	Kaiser Permanente Northwest	Portland	Oregon
United States	Providence Portland Medical Center	Portland	Oregon
United States	Providence Saint Vincent Medical Center	Portland	Oregon
United States	Southern Ohio Medical Center	Portsmouth	Ohio
United States	Kootenai Clinic Cancer Services - Post Falls	Post Falls	Idaho
United States	Pottstown Hospital	Pottstown	Pennsylvania
United States	Geisinger Cancer Services-Pottsville	Pottsville	Pennsylvania
United States	Harrison HealthPartners Hematology and Oncology-Poulsbo	Poulsbo	Washington
United States	Peninsula Cancer Center	Poulsbo	Washington
United States	Kansas City NCI Community Oncology Research Program	Prairie Village	Kansas
United States	Cancer Center of Kansas - Pratt	Pratt	Kansas
United States	Illinois CancerCare-Princeton	Princeton	Illinois
United States	Rocky Mountain Cancer Centers - Pueblo	Pueblo	Colorado
United States	Saint Mary Corwin Medical Center	Pueblo	Colorado
United States	MultiCare Good Samaritan Hospital	Puyallup	Washington
United States	Tacoma/Valley Radiation Oncology Centers-Puyallup	Puyallup	Washington
United States	Aurora Cancer Care-Racine	Racine	Wisconsin
United States	Rapid City Regional Hospital	Rapid City	South Dakota
United States	Kaiser Permanente-Redwood City	Redwood City	California
United States	Beebe Health Campus	Rehoboth Beach	Delaware
United States	Saint Mary's Regional Medical Center	Reno	Nevada
United States	Ascension Saint Mary's Hospital	Rhinelander	Wisconsin
United States	Saint Mary's Hospital	Rhinelander	Wisconsin
United States	Marshfield Medical Center-Rice Lake	Rice Lake	Wisconsin
United States	Kaiser Permanente-Richmond	Richmond	California
United States	Reid Health	Richmond	Indiana
United States	Virginia Cancer Institute	Richmond	Virginia
United States	Virginia Commonwealth University/Massey Cancer Center	Richmond	Virginia
United States	Kaiser Permanente-Riverside	Riverside	California
United States	North Memorial Medical Health Center	Robbinsdale	Minnesota
United States	Mayo Clinic in Rochester	Rochester	Minnesota
United States	University of Rochester	Rochester	New York
United States	UW Health Carbone Cancer Center Rockford	Rockford	Illinois
United States	Penobscot Bay Medical Center	Rockport	Maine
United States	Delbert Day Cancer Institute at PCRMC	Rolla	Missouri
United States	Mercy Clinic-Rolla-Cancer and Hematology	Rolla	Missouri
United States	Hematology Oncology Associates of Central New York-Rome	Rome	New York
United States	Kaiser Permanente-Roseville	Roseville	California
United States	Michigan Cancer Specialists	Roseville	Michigan
United States	Sutter Cancer Centers Radiation Oncology Services-Roseville	Roseville	California
United States	Sutter Roseville Medical Center	Roseville	California
United States	Cancer Care Associates PC	Royal Oak	Michigan
United States	Comprehensive Medical Center PLLC	Royal Oak	Michigan
United States	Hematology Oncology Consultants PC	Royal Oak	Michigan
United States	Oakland Colon Rectal Associates	Royal Oak	Michigan
United States	Oakland Medical Group	Royal Oak	Michigan
United States	William Beaumont Hospital-Royal Oak	Royal Oak	Michigan
United States	Kaiser Permanente - Sacramento	Sacramento	California
United States	Kaiser Permanente-South Sacramento	Sacramento	California
United States	Sutter Medical Center Sacramento	Sacramento	California
United States	Ascension Saint Mary's Hospital	Saginaw	Michigan
United States	Heartland Regional Medical Center	Saint Joseph	Missouri
United States	Mercy Hospital Saint Louis	Saint Louis	Missouri
United States	Missouri Baptist Medical Center	Saint Louis	Missouri
United States	Saint Louis Cancer and Breast Institute-South City	Saint Louis	Missouri
United States	Siteman Cancer Center-South County	Saint Louis	Missouri
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Metro Minnesota Community Oncology Research Consortium	Saint Louis Park	Minnesota
United States	Park Nicollet Clinic - Saint Louis Park	Saint Louis Park	Minnesota
United States	Regions Hospital	Saint Paul	Minnesota
United States	United Hospital	Saint Paul	Minnesota
United States	Siteman Cancer Center at Saint Peters Hospital	Saint Peters	Missouri
United States	Sainte Genevieve County Memorial Hospital	Sainte Genevieve	Missouri
United States	Cancer Center of Kansas - Salina	Salina	Kansas
United States	University Hospital	San Antonio	Texas
United States	University of Texas Health Science Center at San Antonio	San Antonio	Texas
United States	Kaiser Permanente-San Diego Mission	San Diego	California
United States	Kaiser Permanente-San Diego Zion	San Diego	California
United States	California Pacific Medical Center-Pacific Campus	San Francisco	California
United States	Kaiser Permanente-San Francisco	San Francisco	California
United States	Kaiser Permanente-Santa Teresa-San Jose	San Jose	California
United States	Stanford Cancer Center South Bay	San Jose	California
United States	Kaiser Permanente San Leandro	San Leandro	California
United States	Pacific Central Coast Health Center-San Luis Obispo	San Luis Obispo	California
United States	Kaiser Permanente-San Marcos	San Marcos	California
United States	Kaiser Permanente-San Rafael	San Rafael	California
United States	Kootenai Clinic Cancer Services - Sandpoint	Sandpoint	Idaho
United States	Kaiser Permanente Medical Center - Santa Clara	Santa Clara	California
United States	Palo Alto Medical Foundation-Santa Cruz	Santa Cruz	California
United States	Kaiser Permanente-Santa Rosa	Santa Rosa	California
United States	Sutter Pacific Medical Foundation	Santa Rosa	California
United States	Lewis Cancer and Research Pavilion at Saint Joseph's/Candler	Savannah	Georgia
United States	Regional West Medical Center Cancer Center	Scottsbluff	Nebraska
United States	Mayo Clinic in Arizona	Scottsdale	Arizona
United States	Hematology and Oncology Associates of North East Pennsylvania	Scranton	Pennsylvania
United States	TidalHealth Nanticoke / Allen Cancer Center	Seaford	Delaware
United States	FHCC South Lake Union	Seattle	Washington
United States	Fred Hutchinson Cancer Center	Seattle	Washington
United States	Kaiser Permanente Washington	Seattle	Washington
United States	Minor and James Medical PLLC	Seattle	Washington
United States	Pacific Gynecology Specialists	Seattle	Washington
United States	Swedish Medical Center-Ballard Campus	Seattle	Washington
United States	Swedish Medical Center-First Hill	Seattle	Washington
United States	University of Washington Medical Center - Montlake	Seattle	Washington
United States	Virginia Mason Medical Center	Seattle	Washington
United States	Prisma Health Cancer Institute - Seneca	Seneca	South Carolina
United States	UPMC Cancer Center at UPMC Northwest	Seneca	Pennsylvania
United States	Saint Francis Regional Medical Center	Shakopee	Minnesota
United States	HSHS Saint Nicholas Hospital	Sheboygan	Wisconsin
United States	Vince Lombardi Cancer Clinic-Sheboygan	Sheboygan	Wisconsin
United States	Providence Regional Cancer System-Shelton	Shelton	Washington
United States	Jewish Hospital Medical Center South	Shepherdsville	Kentucky
United States	Welch Cancer Center	Sheridan	Wyoming
United States	CHRISTUS Highland Medical Center	Shreveport	Louisiana
United States	LSU Health Sciences Center at Shreveport	Shreveport	Louisiana
United States	Dayton Physicians LLC-Wilson	Sidney	Ohio
United States	Saint Michael Cancer Center	Silverdale	Washington
United States	Mercy Medical Center-Sioux City	Sioux City	Iowa
United States	Saint Luke's Regional Medical Center	Sioux City	Iowa
United States	Siouxland Regional Cancer Center	Sioux City	Iowa
United States	Avera Cancer Institute	Sioux Falls	South Dakota
United States	Sanford Cancer Center Oncology Clinic	Sioux Falls	South Dakota
United States	Sanford USD Medical Center - Sioux Falls	Sioux Falls	South Dakota
United States	Hematology Oncology Associates of Illinois - Skokie	Skokie	Illinois
United States	North Shore Medical Center	Skokie	Illinois
United States	Memorial Hospital of South Bend	South Bend	Indiana
United States	VCU Community Memorial Health Center	South Hill	Virginia
United States	Kaiser Permanente-South San Francisco	South San Francisco	California
United States	Ascension Providence Hospitals - Southfield	Southfield	Michigan
United States	Spartanburg Medical Center	Spartanburg	South Carolina
United States	Abben Cancer Center	Spencer	Iowa
United States	Evergreen Hematology and Oncology PS	Spokane	Washington
United States	MultiCare Deaconess Cancer and Blood Specialty Center - Downtown	Spokane	Washington
United States	MultiCare Deaconess Cancer and Blood Specialty Center - Valley	Spokane Valley	Washington
United States	Baystate Medical Center	Springfield	Massachusetts
United States	Central Illinois Hematology Oncology Center	Springfield	Illinois
United States	CoxHealth South Hospital	Springfield	Missouri
United States	Memorial Medical Center	Springfield	Illinois
United States	Mercy Hospital Springfield	Springfield	Missouri
United States	Southern Illinois University School of Medicine	Springfield	Illinois
United States	Springfield Clinic	Springfield	Illinois
United States	Springfield Regional Cancer Center	Springfield	Ohio
United States	Springfield Regional Medical Center	Springfield	Ohio
United States	Geisinger Medical Group	State College	Pennsylvania
United States	Mitchell Folbe MD PC	Sterling Heights	Michigan
United States	Premier Hematology Oncology Care	Sterling Heights	Michigan
United States	Ascension Saint Michael's Hospital	Stevens Point	Wisconsin
United States	Lakeview Hospital	Stillwater	Minnesota
United States	Kaiser Permanente-Stockton	Stockton	California
United States	Green Bay Oncology - Sturgeon Bay	Sturgeon Bay	Wisconsin
United States	Missouri Baptist Sullivan Hospital	Sullivan	Missouri
United States	Aurora Medical Center in Summit	Summit	Wisconsin
United States	Palo Alto Medical Foundation-Sunnyvale	Sunnyvale	California
United States	BJC Outpatient Center at Sunset Hills	Sunset Hills	Missouri
United States	ProMedica Flower Hospital	Sylvania	Ohio
United States	Hematology Oncology Associates of Central New York-Onondaga Hill	Syracuse	New York
United States	State University of New York Upstate Medical University	Syracuse	New York
United States	Franciscan Research Center-Northwest Medical Plaza	Tacoma	Washington
United States	MultiCare Tacoma General Hospital	Tacoma	Washington
United States	Northwest Medical Specialties PLLC	Tacoma	Washington
United States	Northwest NCI Community Oncology Research Program	Tacoma	Washington
United States	Tacoma/Valley Radiation Oncology Centers-Jackson Hall	Tacoma	Washington
United States	Tacoma/Valley Radiation Oncology Centers-Saint Joe's	Tacoma	Washington
United States	Rocky Mountain Cancer Centers-Thornton	Thornton	Colorado
United States	Mercy Hospital of Tiffin	Tiffin	Ohio
United States	Mercy Health - Saint Anne Hospital	Toledo	Ohio
United States	Mercy Health - Saint Vincent Hospital	Toledo	Ohio
United States	Toledo Clinic Cancer Centers-Toledo	Toledo	Ohio
United States	Toledo Community Hospital Oncology Program CCOP	Toledo	Ohio
United States	University of Toledo	Toledo	Ohio
United States	Cotton O'Neil Cancer Center / Stormont Vail Health	Topeka	Kansas
United States	Smilow Cancer Hospital-Torrington Care Center	Torrington	Connecticut
United States	Claudia BR Herke MD PC	Troy	Michigan
United States	Dayton Physicians LLC - Troy	Troy	Ohio
United States	Hematology Oncology Consultants PC-Troy	Troy	Michigan
United States	Michigan Institute of Urology-Town Center	Troy	Michigan
United States	Upper Valley Medical Center	Troy	Ohio
United States	William Beaumont Hospital - Troy	Troy	Michigan
United States	Smilow Cancer Hospital Care Center-Trumbull	Trumbull	Connecticut
United States	Saint Luke's Cancer Institute - Twin Falls	Twin Falls	Idaho
United States	Vince Lombardi Cancer Clinic-Two Rivers	Two Rivers	Wisconsin
United States	MGC Hematology Oncology-Union	Union	South Carolina
United States	UPMC Uniontown Hospital Radiation Oncology	Uniontown	Pennsylvania
United States	Carle Cancer Center	Urbana	Illinois
United States	The Carle Foundation Hospital	Urbana	Illinois
United States	Kaiser Permanente Medical Center-Vacaville	Vacaville	California
United States	Sutter Cancer Centers Radiation Oncology Services-Vacaville	Vacaville	California
United States	Kaiser Permanente-Vallejo	Vallejo	California
United States	Sutter Solano Medical Center/Cancer Center	Vallejo	California
United States	PeaceHealth Southwest Medical Center	Vancouver	Washington
United States	Ridgeview Medical Center	Waconia	Minnesota
United States	University Hospitals Sharon Health Center	Wadsworth	Ohio
United States	Providence Saint Mary Regional Cancer Center	Walla Walla	Washington
United States	John Muir Medical Center-Walnut Creek	Walnut Creek	California
United States	Kaiser Permanente-Walnut Creek	Walnut Creek	California
United States	Saint John Macomb-Oakland Hospital	Warren	Michigan
United States	Northwestern Medicine Cancer Center Warrenville	Warrenville	Illinois
United States	UPMC Washington Hospital Radiation Oncology	Washington	Pennsylvania
United States	Smilow Cancer Hospital-Waterbury Care Center	Waterbury	Connecticut
United States	MercyOne Waterloo Cancer Center	Waterloo	Iowa
United States	Aurora Cancer Care-Waukesha	Waukesha	Wisconsin
United States	ProHealth Waukesha Memorial Hospital	Waukesha	Wisconsin
United States	UW Cancer Center at ProHealth Care	Waukesha	Wisconsin
United States	Aspirus Regional Cancer Center	Wausau	Wisconsin
United States	Marshfield Clinic-Wausau Center	Wausau	Wisconsin
United States	Fulton County Health Center	Wauseon	Ohio
United States	Aurora Cancer Care-Milwaukee West	Wauwatosa	Wisconsin
United States	Cancer Center of Kansas - Wellington	Wellington	Kansas
United States	Aurora West Allis Medical Center	West Allis	Wisconsin
United States	Henry Ford West Bloomfield Hospital	West Bloomfield	Michigan
United States	University of Cincinnati Cancer Center-West Chester	West Chester	Ohio
United States	Mercy Medical Center-West Lakes	West Des Moines	Iowa
United States	Reading Hospital	West Reading	Pennsylvania
United States	Saint Ann's Hospital	Westerville	Ohio
United States	UH Seidman Cancer Center at Saint John Medical Center	Westlake	Ohio
United States	Ascension Saint Clare's Hospital	Weston	Wisconsin
United States	Diagnostic and Treatment Center	Weston	Wisconsin
United States	Marshfield Medical Center - Weston	Weston	Wisconsin
United States	SCL Health Lutheran Medical Center	Wheat Ridge	Colorado
United States	Ascension Via Christi Hospitals Wichita	Wichita	Kansas
United States	Associates In Womens Health	Wichita	Kansas
United States	Cancer Center of Kansas - Wichita	Wichita	Kansas
United States	Cancer Center of Kansas-Wichita Medical Arts Tower	Wichita	Kansas
United States	Geisinger Wyoming Valley/Henry Cancer Center	Wilkes-Barre	Pennsylvania
United States	UPMC Susquehanna	Williamsport	Pennsylvania
United States	Rice Memorial Hospital	Willmar	Minnesota
United States	Christiana Care Health System-Wilmington Hospital	Wilmington	Delaware
United States	Winchester Hospital	Winchester	Massachusetts
United States	Cancer Center of Kansas - Winfield	Winfield	Kansas
United States	Wake Forest University Health Sciences	Winston-Salem	North Carolina
United States	Aspirus Cancer Care - Wisconsin Rapids	Wisconsin Rapids	Wisconsin
United States	Marshfield Clinic - Wisconsin Rapids Center	Wisconsin Rapids	Wisconsin
United States	Minnesota Oncology Hematology PA-Woodbury	Woodbury	Minnesota
United States	Kaiser Permanente-Woodland Hills	Woodland Hills	California
United States	UMass Memorial Medical Center - University Campus	Worcester	Massachusetts
United States	Wright-Patterson Medical Center	Wright-Patterson Air Force Base	Ohio
United States	Lankenau Medical Center	Wynnewood	Pennsylvania
United States	North Star Lodge Cancer Center at Yakima Valley Memorial Hospital	Yakima	Washington
United States	Providence Regional Cancer System-Yelm	Yelm	Washington
United States	Rush-Copley Healthcare Center	Yorkville	Illinois
United States	Genesis Healthcare System Cancer Care Center	Zanesville	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Distribution of Genetic Abnormalities Before and After Treatment	Genetic abnormalities are assessed at baseline and longitudinally during treatment as well as after treatment. Distribution of genetic abnormalities are reported.	Assessed at baseline, and 3, 6, 12, 15, 18, 24, 36 months
Other	T-cell Counts at 12 Months	T-cell counts will be measured at 12 months.	Assessed at 12 months
Other	Association Between Single Nucleotide Polymorphisms (SNPs) and PFS	PFS was defined as time from randomization to progression or death, whichever occurred first. Progression is characterized by any of the following: = 50% increase from nadir since start of treatment (tx) in the sum of the products of =2 lymph nodes on 2 consecutive examinations 2 weeks apart; = 50% increase from nadir since start of tx in the size of liver and/or spleen; = 50% increase in the absolute number of circulating lymphocytes not due to tumor flare reaction. The absolute lymphocyte count must be = 5x10^9/L to qualify as progression.; Transformation to a more aggressive histology. For patients who achieve a complete response or nodular partial response, progression is defined as recurrence of circulating leukemia cell clone in the peripheral blood and an absolute lymphocyte count > 5x10^9/L and/or recurrence of palpable lymphadenopathy > 1.5 cm by physical exam.; The distribution of PFS by SNPs will be reported.	Assessed every 3 months until progression; after progression, assessed every 3 months for first 2 years, every 6 months for years 3-5
Other	Prognostic Model to Predict PFS	A prognostic model that incorporates clinical and biologic characters to predict PFS will be developed.	Assessed every 3 months until progression; after progression, assessed every 3 months for first 2 years, every 6 months for years 3-5
Other	Signaling Networks Downstream of the B-cell Receptor	Evaluation of signaling networks downstream of the B-cell receptor in patients receiving Ibrutinib-based therapy.	Assessed at baseline and 3, 6, 12, 15, 18, 24, 36 months
Other	Collection of Relapse Samples	Collection of relapse samples to study mechanisms of resistance to protocol treatments.	Assessed at relapse
Primary	Progression-free Survival (PFS) Rate at 3 Years	PFS was defined as the time from randomization to CLL progression or death, whichever occurred first. Progression is characterized by any of the following: = 50% increase from nadir since start of treatment (tx) in the sum of the products of at least 2 lymph nodes on 2 consecutive examinations 2 weeks apart; = 50% increase from nadir since start of tx in the size of liver and/or spleen; = 50% increase in the absolute number of circulating lymphocytes not due to tumor flare reaction. The absolute lymphocyte count must be = 5x10^9/L to qualify as disease progression.; Transformation to a more aggressive histology (e.g. Richter's syndrome or prolymphocytic leukemia with > 55% prolymphocytes). For patients who achieve a complete response or nodular partial response, progression is defined as recurrence of circulating leukemia cell clone in the peripheral blood and an absolute lymphocyte count > 5x10^9/L and/or recurrence of palpable lymphadenopathy > 1.5 cm by physical exam.	Assessed every 3 months until progression up to 4 years and 8 months
Secondary	Overall Survival (OS) Rate at 3 Years	Overall survival was defined as time from randomization to death from any cause or date last known alive. Overall survival rate at 3 years was estimated using the method of Kaplan-Meier.	Assessed every 3 months until progression; after progression, assessed every 3 months for first 2 years, every 6 months for years 3-5, up to 4 years and 8 months
Secondary	The Functional Assessment of Cancer Therapy - Leukemia (FACT-Leu) Trial Outcome Index (TOI) Score at 6 Months	The Functional Assessment of Cancer Therapy - Leukemia (FACT-Leu) Trial Outcome Index (TOI) is comprised of the physical well-being (PWB) and functional well-being (FWB) components of the FACT-General (FACT-G) and the leukemia subscale. The FACT-Leu TOI contains a total of 31 items, with scores ranging from 0 to 124. The higher the score, the better the quality of life (QOL).	Assessed at 6 months
Secondary	The Functional Assessment of Cancer Therapy - Leukemia (FACT-Leu) Trial Outcome Index (TOI) Score at 12 Months	The Functional Assessment of Cancer Therapy - Leukemia (FACT-Leu) Trial Outcome Index (TOI) is comprised of the physical well-being (PWB) and functional well-being (FWB) components of the FACT-General (FACT-G) and the leukemia subscale. The FACT-Leu TOI contains a total of 31 items, with scores ranging from 0 to 124. The higher the score, the better the quality of life (QOL).	Assessed at 12 months
Secondary	The Association Between Baseline Rai Stage and Complete Response (CR) Rate	Patients are classified as stage 0-IV according to the Rai system and categorized into one of the three risk groups: Low risk - Stage 0 Intermediate risk - Stage I or II High risk - Stage III or IV; CR requires all of the following for at least 2 months: Absence of lymphadenopathy by physical examination on 2 occasions at least 4 weeks apart and appropriate radiographic techniques. For patients whose only measurable disease at the time of enrollment is on CT scan, a CT scan is required and all lymph nodes must be = 1.5 cm before classifying the patient a CR.; Absence of hepatomegaly or splenomegaly by physical examination; Absence of constitutional symptoms due to disease; Normal complete blood count; One marrow aspirate and biopsy should be performed 52 weeks after Day 1 of cycle 1 among patients with clinical and laboratory evidence of a CR to document a CR. The marrow sample must be at least normocellular with < 30% of nucleated cells being lymphocytes.	Assessed at baseline, every 3 months for the first 2 years, and every 6 months for years 3-5
Secondary	Progression-free Survival (PFS) by Measurable Residual Disease (MDR) Status at 2 Years	PFS was defined as time from randomization to progression or death. Progression is characterized by any of the following: = 50% increase from nadir since start of treatment (tx) in the sum of the products of = 2 lymph nodes on 2 consecutive exams 2 weeks apart; = 50% increase from nadir since start of tx in the size of liver and/or spleen; = 50% increase in the absolute number of circulating lymphocytes not due to tumor flare reaction. The absolute lymphocyte count must be = 5x10^9/L to qualify as progression.; Transformation to a more aggressive histology. For patients with a complete response or nodular partial response, progression is defined as recurrence of circulating leukemia cell clone in the peripheral blood and an absolute lymphocyte count > 5x10^9/L and/or recurrence of palpable lymphadenopathy >1.5 cm by physical exam.; MRD status was evaluated at 2 years and samples with <=20 monotypic events or an MRD level of <10^-4 were classified as undetectable MRD.	Assessed every 3 months until progression up to 5 years