Rituximab and Bendamustine Hydrochloride, Rituximab and Ibrutinib, or Ibrutinib Alone in Treating Older Patients With Previously Untreated Chronic Lymphocytic Leukemia

Stage IV Chronic Lymphocytic Leukemia Clinical Trial

Official title:

A Randomized Phase III Study of Bendamustine Plus Rituximab Versus Ibrutinib Plus Rituximab Versus Ibrutinib Alone in Untreated Older Patients (>/= 65 Years of Age) With Chronic Lymphocytic Leukemia (CLL)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01886872
• Other study ID #: NCI-2013-01220
• Secondary ID: NCI-2013-01220AL
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: December 9, 2013
• Est. completion date: January 30, 2025

Study information

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

Clinical Trial Summary

This randomized phase III trial studies rituximab with bendamustine hydrochloride or ibrutinib to see how well they work compared to ibrutinib alone in treating older patients with previously untreated chronic lymphocytic leukemia. Monoclonal antibodies, such as rituximab, may block cancer growth in different ways by targeting certain cells. Drugs used in chemotherapy, such as bendamustine hydrochloride, 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. Ibrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. It is not yet known whether rituximab with bendamustine hydrochloride may work better than rituximab and ibrutinib or ibrutinib alone in treating chronic lymphocytic leukemia.

Description:

PRIMARY OBJECTIVE:

I. To determine whether progression free survival (PFS) is superior after therapy with bendamustine hydrochloride (bendamustine) in combination with rituximab, ibrutinib alone, or ibrutinib in combination with rituximab in patients age 65 or older with previously untreated chronic lymphocytic leukemia (CLL).

SECONDARY OBJECTIVES:

I. To determine 2-year PFS in each of the three treatment arms. II. To determine which treatment arm produces superior overall survival (OS). III. To determine the complete response (CR) rate, complete and nodular partial response (CR/nPR) rate, and overall response (PR+nPR+CR) rate (ORR) among the three treatment arms and compare these arms.

IV. To determine the impact of minimal residual disease (MRD)-negative disease at time of CR documentation and at 2 years on PFS and OS in each of the treatment arms.

V. To determine duration of response after each of the three treatments and compare these treatment arms.

VI. To determine toxicity and tolerability of the three treatment regimens. VII. To determine response and PFS of patients initially on the bendamustine in combination with rituximab arm who cross over to ibrutinib.

OTHER PRE-SPECIFIED OBJECTIVES:

I. To determine whether baseline cytogenetic markers, Zap-70 methylation, IgVH mutational status, or select deoxyribonucleic acid (DNA) mutations predict outcomes or time to response in these three arms.

II. To determine whether local fluorescence in situ hybridization (FISH) results for del(11q22.3) and del(17p13.1) are consistent with central analysis.

III. To determine whether baseline micro ribonucleic acid (RNA) and gene expression markers are correlated with clinical outcomes of interest (e.g. progression-free and alive at 2 years versus not), as well as to explore changes in microRNA expression from baseline to post-treatment time points, with a focus on those with persistent lymphocytosis and relapse.

IV. To determine whether eradication of MRD predicts longer duration of response with standard therapy and ibrutinib-based regimens.

V. To describe the baseline functional status, comorbid medical conditions, and number of medications of older CLL patients who meet criteria for therapy.

VI. To determine how functional status changes with therapy using baseline to 3-month evaluation and end-of-study/2-year evaluation; to determine whether this change is different among the treatment groups.

VII. To determine whether geriatric assessment variables known to be associated with chemotherapy toxicity in other disease groups can also predict therapy-associated toxicity in the CLL population.

VIII. To assess whether the FCGR3A polymorphism (rs396991) is correlated with depth of response (MRD status) to ibrutinib plus rituximab after 6 cycles, with secondary endpoints CR rate, rapidity of response, and progression-free survival (PFS).

IX. To assess whether C1QA polymorphism (rs172378) is correlated with MRD status, CR rate, rapidity of response, and PFS.

OUTLINE: Patients are randomized to 1 of 3 treatment arms.

ARM I: Patients receive rituximab intravenously (IV) on day 1 (day 0 course 1) and bendamustine hydrochloride IV over 30 minutes on days 1-2. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients experiencing disease progression may crossover to Arm II.

ARM II: Patients receive ibrutinib orally (PO) daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

ARM III: Patients receive ibrutinib as in Arm II. Patients receive rituximab IV on days 1, 8, 15, and 22 of course 2 and on day 1 of courses 3-6. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 6 months for up to 10 years.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 547
• Est. completion date: January 30, 2025
• Est. primary completion date: August 7, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 65 Years and older

Eligibility

Inclusion Criteria:

• PRE-REGISTRATION (STEP 0)

• All patients are REQUIRED to be pre-registered to A041202 in order to submit peripheral blood to the Alliance Hematologic Malignancy Biorepository (HEME) for central Zap-70 methylation. This specimen submission is mandatory prior to registration as results will be used for stratification

• REGISTRATION (STEP 1)

• Patients must be diagnosed with CLL in accordance with International Workshop on Chronic Lymphocytic Leukemia (IWCLL) 2008 criteria that includes all of the following:

• >= 5 x 10^9 B lymphocytes (5000/uL) in the peripheral blood

• On morphologic review, the leukemic cells must be small mature lymphocytes, and prolymphocytes must not exceed 55% of the blood lymphocytes

• CLL cells on immunophenotype (performed locally) must reveal a clonal B-cell population, which express the B cell surface markers of CD19 and CD20, as well as the T-cell antigen CD5; patients with bright surface immunoglobulin expression or lack of CD23 expression in > 10% of cells must lack t(11;14) translocation by interphase cytogenetics

• Patients must be intermediate or high-risk Rai stage CLL

• Intermediate risk (formerly Rai stage I/II) is defined by lymphocytosis plus enlarged lymph nodes at any site, with or without hepatomegaly or splenomegaly

• High risk (formerly Rai stage III/IV) is defined by lymphocytosis with or without enlarged nodes and spleen plus disease-related anemia (hemoglobin < 11 g/dL) or thrombocytopenia (platelet count < 100 x 10^9/L) that is not attributable to autoimmune hemolytic anemia or thrombocytopenia

• Patients must meet criteria for treatment as defined by IWCLL 2008 guidelines which includes at least one of the following criteria:

• Evidence of marrow failure as manifested by the development or worsening of anemia or thrombocytopenia (not attributable to autoimmune hemolytic anemia or thrombocytopenia)

• Massive (>= 6 cm below the costal margin), progressive or symptomatic splenomegaly

• Massive nodes (>= 10 cm) or progressive or symptomatic lymphadenopathy

• Autoimmune anemia and/or thrombocytopenia that is poorly responsive to standard therapy

• Constitutional symptoms, which include any of the following:

• Unintentional weight loss of 10% or more within 6 months

• Significant fatigue

• Fevers > 100.5 degrees F for 2 weeks or more without evidence of infection

• Night sweats > 1 month without evidence of infection

• Age >= 65 years

• Eastern Cooperative Oncology Group (ECOG) performance status 0-2

• Patients with active hepatitis B defined by hepatitis B surface antigen positivity or core antibody positivity in the presence of hepatitis B DNA are not eligible for this study; patients with a positive hepatitis B core antibody but with negative hepatitis B DNA may participate, but must have hepatitis serologies and hepatitis B DNA monitored periodically by the treating physician

• Intravenous immunoglobulin (IVIG) can cause a false positive hepatitis B serology; if patients receiving routine IVIG have core antibody or surface antigen positivity without evidence of active viremia (negative hepatitis B DNA) they may still participate in the study, but should have hepatitis serologies and hepatitis B DNA monitored periodically by the treating physician

• Patients with class III or class IV heart failure by New York Heart Association, those with unstable angina, and those with uncontrolled arrhythmia are not eligible

• Patients who have had a myocardial infarction, intracranial bleed, or stroke within the past 6 months are not eligible

• Patients with known human immunodeficiency virus (HIV) are eligible if their CD4 count is >= 350 cells/mm^3 and if they are not taking prohibited CYP-interacting medications

• Patients may not have had major surgery within 10 days of enrollment, or minor surgery within 7 days of enrollment; examples of minor surgery include dental surgery, insertion of a venous access device, skin biopsy, or aspiration of a joint; the decision about whether a surgery is major or minor can be made at the discretion of the treating physician

• Absolute neutrophil count (ANC) >= 1,000/uL unless due to bone marrow involvement

• Aspartate aminotransferase (AST) or alanine aminotransferase (AST) =< 2.5 x upper limits of normal except if due to disease infiltration of the liver

• Bilirubin =< 1.5 x upper limits of normal (unless due to liver involvement, hemolysis, or Gilbert's disease)

• Creatinine clearance >= 40 mL/min

• To be calculated by modified Cockcroft-Gault formula

• Platelet count (untransfused) >= 30,000/uL

Exclusion Criteria:

• Prior treatment

• Patients must not have had prior therapy for CLL (except palliative steroids or treatment of autoimmune complications of CLL with rituximab or steroids)

• Treatment with rituximab and/or high dose corticosteroids for autoimmune complications of CLL must be complete at least 4 weeks prior to enrollment; palliative steroids must be at a dose not higher than 20 mg/day of prednisone or equivalent corticosteroid at the time of registration

• Patients must not be receiving active systemic anticoagulation with heparin or warfarin; patients must be off warfarin therapy for at least 30 days prior to enrollment

• Patients must not have any history of Richter's transformation or prolymphocytic leukemia (prolymphocytes in blood > 55%)

• Patients must not require more than 20 mg prednisone or equivalent corticosteroid daily

• Patients must not have uncontrolled active systemic infection requiring intravenous antibiotics

• Patients must not have continued requirement for therapy with a strong cytochrome P450 3A4/5 (CYP3A4/5) inhibitor or inducer

• Patients must not have a known allergy to mannitol

• Patients must not have prior significant hypersensitivity to rituximab (not including infusion reactions)

Related Conditions & MeSH terms

• Leukemia
• Leukemia, Lymphocytic, Chronic, B-Cell
• Leukemia, Lymphoid
• Stage I Chronic Lymphocytic Leukemia
• Stage II Chronic Lymphocytic Leukemia
• Stage III Chronic Lymphocytic Leukemia
• Stage IV Chronic Lymphocytic Leukemia

Intervention

Drug:
• Bendamustine Hydrochloride
Given IV
• Ibrutinib
Given PO

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

Biological:
• Rituximab
Given IV

Locations

Country	Name	City	State
Canada	Tom Baker Cancer Centre	Calgary	Alberta
Canada	CSSS Champlain-Charles Le Moyne	Greenfield Park	Quebec
Canada	QEII Health Sciences Centre/Nova Scotia Health Authority	Halifax	Nova Scotia
Canada	Juravinski Cancer Centre at Hamilton Health Sciences	Hamilton	Ontario
Canada	Kingston Health Sciences Centre	Kingston	Ontario
Canada	London Regional Cancer Program	London	Ontario
Canada	The Moncton Hospital	Moncton	New Brunswick
Canada	CHUM - Centre Hospitalier de l'Universite de Montreal	Montreal	Quebec
Canada	CHUM - Hopital Notre-Dame	Montreal	Quebec
Canada	Jewish General Hospital	Montreal	Quebec
Canada	McGill University Department of Oncology	Montreal	Quebec
Canada	Stronach Regional Health Centre at Southlake	Newmarket	Ontario
Canada	Lakeridge Health Oshawa	Oshawa	Ontario
Canada	Ottawa Hospital and Cancer Center-General Campus	Ottawa	Ontario
Canada	Allan Blair Cancer Centre	Regina	Saskatchewan
Canada	Saskatoon Cancer Centre	Saskatoon	Saskatchewan
Canada	Health Sciences North	Sudbury	Ontario
Canada	Humber River Hospital	Toronto	Ontario
Canada	Michael Garron Hospital	Toronto	Ontario
Canada	Odette Cancer Centre- Sunnybrook Health Sciences Centre	Toronto	Ontario
Canada	University Health Network-Princess Margaret Hospital	Toronto	Ontario
United States	Pali Momi Medical Center	'Aiea	Hawaii
United States	Queen's Cancer Center - Pearlridge	'Aiea	Hawaii
United States	The Cancer Center of Hawaii-Pali Momi	'Aiea	Hawaii
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	Presbyterian Kaseman Hospital	Albuquerque	New Mexico
United States	University of New Mexico Cancer Center	Albuquerque	New Mexico
United States	Lehigh Valley Hospital-Cedar Crest	Allentown	Pennsylvania
United States	AdventHealth Altamonte	Altamonte Springs	Florida
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	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 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	AnMed Health Cancer Center	Anderson	South Carolina
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	Hope Women's Cancer Centers-Asheville	Asheville	North Carolina
United States	Messino Cancer Centers	Asheville	North Carolina
United States	Mission Hospital	Asheville	North Carolina
United States	Mountain Radiation Oncology PA	Asheville	North Carolina
United States	Emory University Hospital/Winship Cancer Institute	Atlanta	Georgia
United States	Northside Hospital	Atlanta	Georgia
United States	Hematology Oncology Associates of Central New York-Auburn	Auburn	New York
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	Kaiser Permanente-Baldwin Park	Baldwin Park	California
United States	Greater Baltimore Medical Center	Baltimore	Maryland
United States	MedStar Franklin Square Medical Center/Weinberg Cancer Institute	Baltimore	Maryland
United States	Saint Agnes Hospital	Baltimore	Maryland
United States	Sinai Hospital of Baltimore	Baltimore	Maryland
United States	Eastern Maine Medical Center	Bangor	Maine
United States	Flaget Memorial Hospital	Bardstown	Kentucky
United States	Louisiana Hematology Oncology Associates LLC	Baton Rouge	Louisiana
United States	LSU Health Baton Rouge-North Clinic	Baton Rouge	Louisiana
United States	Mary Bird Perkins Cancer Center	Baton Rouge	Louisiana
United States	Ochsner Health Center-Summa	Baton Rouge	Louisiana
United States	Our Lady of the Lake Physician Group	Baton Rouge	Louisiana
United States	Bronson Battle Creek	Battle Creek	Michigan
United States	McLaren Cancer Institute-Bay City	Bay City	Michigan
United States	Cleveland Clinic Cancer Center Beachwood	Beachwood	Ohio
United States	UHHS-Chagrin Highlands Medical Center	Beachwood	Ohio
United States	UPMC-Heritage Valley Health System Beaver	Beaver	Pennsylvania
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	Southwestern Vermont Medical Center	Bennington	Vermont
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	Boston Medical Center	Boston	Massachusetts
United States	Brigham and Women's Hospital	Boston	Massachusetts
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Massachusetts General Hospital Cancer Center	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	Transylvania Regional Hospital	Brevard	North Carolina
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	Wellmont Medical Associates Oncology and Hematology-Bristol	Bristol	Tennessee
United States	Maimonides Medical Center	Brooklyn	New York
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	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	Mercy Hospital	Cedar Rapids	Iowa
United States	Oncology Associates at Mercy Medical Center	Cedar Rapids	Iowa
United States	Physicians' Clinic of Iowa PC	Cedar Rapids	Iowa
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	UNC Lineberger Comprehensive Cancer Center	Chapel Hill	North Carolina
United States	Geauga Hospital	Chardon	Ohio
United States	Bon Secours Saint Francis Hospital	Charleston	South Carolina
United States	Charleston Oncology - Roper	Charleston	South Carolina
United States	Charleston Oncology - Saint Francis	Charleston	South Carolina
United States	Lowcountry Hematology Oncology PA-North Charleston	Charleston	South Carolina
United States	Lowcountry Hematology Oncology PA-West Ashley	Charleston	South Carolina
United States	Medical University of South Carolina	Charleston	South Carolina
United States	Roper Hospital	Charleston	South Carolina
United States	West Virginia University Charleston Division	Charleston	West Virginia
United States	University of Virginia Cancer Center	Charlottesville	Virginia
United States	Erlanger Medical Center	Chattanooga	Tennessee
United States	Memorial Hospital	Chattanooga	Tennessee
United States	Saint Luke's Hospital	Chesterfield	Missouri
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	University of Illinois	Chicago	Illinois
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	McLaren Cancer Institute-Clarkston	Clarkston	Michigan
United States	Case Western Reserve University	Cleveland	Ohio
United States	Cleveland Clinic Cancer Center/Fairview Hospital	Cleveland	Ohio
United States	Cleveland Clinic Foundation	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	MU Health - University Hospital/Ellis Fischel Cancer Center	Columbia	Missouri
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 Health Center West	Columbus	Ohio
United States	Ohio State University Comprehensive Cancer Center	Columbus	Ohio
United States	Riverside Methodist Hospital	Columbus	Ohio
United States	The Mark H Zangmeister Center	Columbus	Ohio
United States	Huron Valley-Sinai Hospital	Commerce	Michigan
United States	John Muir Medical Center-Concord	Concord	California
United States	New Hampshire Oncology Hematology PA-Concord	Concord	New Hampshire
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	Mary Bird Perkins Cancer Center - Covington	Covington	Louisiana
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	Michiana Hematology Oncology PC-Crown Point	Crown Point	Indiana
United States	UPMC Western Maryland	Cumberland	Maryland
United States	Northside Hospital-Forsyth	Cumming	Georgia
United States	Parkland Memorial Hospital	Dallas	Texas
United States	UT Southwestern/Simmons Cancer Center-Dallas	Dallas	Texas
United States	Danbury Hospital	Danbury	Connecticut
United States	Carle at The Riverfront	Danville	Illinois
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	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	Heartland Cancer Research NCORP	Decatur	Illinois
United States	UM Sylvester Comprehensive Cancer Center at Deerfield Beach	Deerfield Beach	Florida
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	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	Parkland Medical Center	Derry	New Hampshire
United States	Iowa-Wide Oncology Research Coalition NCORP	Des Moines	Iowa
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	Delaware County Memorial Hospital	Drexel Hill	Pennsylvania
United States	City of Hope Comprehensive Cancer Center	Duarte	California
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	Saint Luke's Hospital of Duluth	Duluth	Minnesota
United States	Mercy Medical Center	Durango	Colorado
United States	Southwest Oncology PC	Durango	Colorado
United States	Duke University Medical Center	Durham	North Carolina
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	Pocono Medical Center	East Stroudsburg	Pennsylvania
United States	Hematology Oncology Associates of Central New York-East Syracuse	East Syracuse	New York
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	Elkhart Clinic	Elkhart	Indiana
United States	Elkhart General Hospital	Elkhart	Indiana
United States	Michiana Hematology Oncology PC-Elkhart	Elkhart	Indiana
United States	Mercy Cancer Center-Elyria	Elyria	Ohio
United States	Newman Regional Health	Emporia	Kansas
United States	Englewood Hospital and Medical Center	Englewood	New Jersey
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	Ephrata Cancer Center	Ephrata	Pennsylvania
United States	Ephrata Community Hospital	Ephrata	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	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	Lake Region Healthcare Corporation-Cancer Care	Fergus Falls	Minnesota
United States	Blanchard Valley Hospital	Findlay	Ohio
United States	Simonds-Sinon Regional Cancer Center	Fitchburg	Massachusetts
United States	Genesys Hurley Cancer Institute	Flint	Michigan
United States	Hurley Medical Center	Flint	Michigan
United States	Singh and Arora Hematology Oncology PC	Flint	Michigan
United States	McLeod Regional Medical Center	Florence	South Carolina
United States	Aurora Health Center-Fond du Lac	Fond Du Lac	Wisconsin
United States	Kaiser Permanente-Fontana	Fontana	California
United States	Poudre Valley Hospital	Fort Collins	Colorado
United States	McFarland Clinic - Trinity Cancer Center	Fort Dodge	Iowa
United States	Holy Cross Hospital	Fort Lauderdale	Florida
United States	Cancer Center of Kansas - Fort Scott	Fort Scott	Kansas
United States	Fort Wayne Medical Oncology and Hematology Inc-Parkview	Fort Wayne	Indiana
United States	Angel Medical Center	Franklin	North Carolina
United States	Atrium Medical Center-Middletown Regional Hospital	Franklin	Ohio
United States	Frederick Memorial Hospital	Frederick	Maryland
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	Saint Catherine Hospital	Garden City	Kansas
United States	Northwestern Medicine Cancer Center Delnor	Geneva	Illinois
United States	Aurora Health Care Germantown Health Center	Germantown	Wisconsin
United States	Adams Cancer Center	Gettysburg	Pennsylvania
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	Altru Cancer Center	Grand Forks	North Dakota
United States	Nebraska Cancer Specialists/Oncology Hematology West PC	Grand Island	Nebraska
United States	Cancer Research Consortium of West Michigan NCORP	Grand Rapids	Michigan
United States	Corewell Health Grand Rapids Hospitals - Butterworth Hospital	Grand Rapids	Michigan
United States	Trinity Health Grand Rapids Hospital	Grand Rapids	Michigan
United States	Saint Rose Ambulatory and Surgery Center	Great Bend	Kansas
United States	Benefis Sletten Cancer Institute	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	East Carolina University	Greenville	North Carolina
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	Smilow Cancer Hospital Care Center - Guilford	Guilford	Connecticut
United States	Virginia Oncology Associates-Hampton	Hampton	Virginia
United States	WellSpan Medical Oncology and Hematology	Hanover	Pennsylvania
United States	Kaiser Permanente - Harbor City	Harbor City	California
United States	Smilow Cancer Hospital Care Center at Saint Francis	Hartford	Connecticut
United States	HaysMed	Hays	Kansas
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	Hinsdale Hematology Oncology Associates Incorporated	Hinsdale	Illinois
United States	Pulmonary Medicine Center of Chattanooga-Hixson	Hixson	Tennessee
United States	Hawaii Cancer Care Inc - Waterfront Plaza	Honolulu	Hawaii
United States	Hawaii Cancer Care Inc-Liliha	Honolulu	Hawaii
United States	Kaiser Permanente Moanalua Medical Center	Honolulu	Hawaii
United States	Kapiolani Medical Center for Women and Children	Honolulu	Hawaii
United States	Kuakini Medical Center	Honolulu	Hawaii
United States	Queen's Cancer Center - Kuakini	Honolulu	Hawaii
United States	Queen's Medical Center	Honolulu	Hawaii
United States	Straub Clinic and Hospital	Honolulu	Hawaii
United States	The Cancer Center of Hawaii-Liliha	Honolulu	Hawaii
United States	University of Hawaii Cancer Center	Honolulu	Hawaii
United States	CHI Saint Vincent Cancer Center Hot Springs	Hot Springs	Arkansas
United States	Mary Bird Perkins Cancer Center - Houma	Houma	Louisiana
United States	Edwards Comprehensive Cancer Center	Huntington	West Virginia
United States	Saint Mary's Medical Center	Huntington	West Virginia
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	Cleveland Clinic Cancer Center Independence	Independence	Ohio
United States	Iowa City VA Healthcare System	Iowa City	Iowa
United States	University of Iowa/Holden Comprehensive Cancer Center	Iowa City	Iowa
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	University of Mississippi Medical Center	Jackson	Mississippi
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	McFarland Clinic - Jefferson	Jefferson	Iowa
United States	MU Health Care Goldschmidt Cancer Center	Jefferson City	Missouri
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	Jupiter Medical Center	Jupiter	Florida
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	North Kansas City Hospital	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	The University of Kansas Cancer Center-South	Kansas City	Missouri
United States	University Health Truman Medical Center	Kansas City	Missouri
United States	University of Kansas Cancer Center	Kansas City	Kansas
United States	University of Kansas Cancer Center - North	Kansas City	Missouri
United States	University of Kansas Cancer Center-West	Kansas City	Kansas
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	Aurora Cancer Care-Kenosha South	Kenosha	Wisconsin
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	AdventHealth Kissimmee	Kissimmee	Florida
United States	Community Howard Regional Health	Kokomo	Indiana
United States	Gundersen Lutheran Medical Center	La Crosse	Wisconsin
United States	IU Health La Porte Hospital	La Porte	Indiana
United States	Providence Regional Cancer System-Lacey	Lacey	Washington
United States	LRGHealthcare-Lakes Region General Hospital	Laconia	New Hampshire
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	Rocky Mountain Cancer Centers-Lakewood	Lakewood	Colorado
United States	Saint Anthony Hospital	Lakewood	Colorado
United States	Saint Clare Hospital	Lakewood	Washington
United States	Carolina Blood and Cancer Care Associates PA-Lancaster	Lancaster	South Carolina
United States	Fairfield Medical Center	Lancaster	Ohio
United States	Lancaster Radiation Oncology	Lancaster	Ohio
United States	Karmanos Cancer Institute at McLaren Greater Lansing	Lansing	Michigan
United States	University of Michigan Health - Sparrow Lansing	Lansing	Michigan
United States	McLaren Cancer Institute-Lapeer Region	Lapeer	Michigan
United States	Memorial Medical Center - Las Cruces	Las Cruces	New Mexico
United States	Alliance for Childhood Diseases/Cure 4 the Kids Foundation	Las Vegas	Nevada
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	Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center	Lebanon	New Hampshire
United States	Saint Luke's East - Lee's Summit	Lee's Summit	Missouri
United States	University of Kansas Cancer Center - Lee's Summit	Lee's Summit	Missouri
United States	Beebe Medical Center	Lewes	Delaware
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	Wilcox Memorial Hospital and Kauai Medical Clinic	Lihue	Hawaii
United States	Lima Memorial Hospital	Lima	Ohio
United States	Saint Elizabeth Regional Medical Center	Lincoln	Nebraska
United States	Littleton Adventist Hospital	Littleton	Colorado
United States	Rocky Mountain Cancer Centers-Littleton	Littleton	Colorado
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	Cedars Sinai Medical Center	Los Angeles	California
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	Centra Alan B Pearson Regional Cancer Center	Lynchburg	Virginia
United States	Illinois CancerCare-Macomb	Macomb	Illinois
United States	Dartmouth Cancer Center - Manchester	Manchester	New Hampshire
United States	Solinsky Center for Cancer Care	Manchester	New Hampshire
United States	North Shore University Hospital	Manhasset	New York
United States	Holy Family Memorial Hospital	Manitowoc	Wisconsin
United States	Cleveland Clinic Cancer Center Mansfield	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	Bay Area Medical Center	Marinette	Wisconsin
United States	Mission Hospital McDowell	Marion	North Carolina
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	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	Hillcrest Hospital Cancer Center	Mayfield Heights	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	University of Miami Miller School of Medicine-Sylvester Cancer Center	Miami	Florida
United States	Mount Sinai Medical Center	Miami Beach	Florida
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	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	Minneapolis VA Medical Center	Minneapolis	Minnesota
United States	Marshfield Clinic-Minocqua Center	Minocqua	Wisconsin
United States	Trinity Cancer Care Center	Minot	North Dakota
United States	Memorial Regional Cancer Center Day Road	Mishawaka	Indiana
United States	Michiana Hematology Oncology PC-Mishawaka	Mishawaka	Indiana
United States	Saint Joseph Regional Medical Center-Mishawaka	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	Illinois CancerCare-Monmouth	Monmouth	Illinois
United States	Mercy Memorial Hospital	Monroe	Michigan
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	McLaren Cancer Institute-Macomb	Mount Clemens	Michigan
United States	Lowcountry Hematology Oncology PA-Mount Pleasant	Mount Pleasant	South Carolina
United States	McLaren Cancer Institute-Central Michigan	Mount Pleasant	Michigan
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	Trinity Health Muskegon Hospital	Muskegon	Michigan
United States	Saint Luke's Cancer Institute - Nampa	Nampa	Idaho
United States	Dartmouth Cancer Center - Nashua	Nashua	New Hampshire
United States	The Hospital of Central Connecticut	New Britain	Connecticut
United States	Rutgers Cancer Institute of New Jersey	New Brunswick	New Jersey
United States	Yale University	New Haven	Connecticut
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	NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center	New York	New York
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	Newton-Wellesley Hospital	Newton	Massachusetts
United States	Carle Cancer Institute Normal	Normal	Illinois
United States	Yale-New Haven Hospital North Haven Medical Center	North Haven	Connecticut
United States	Southwest VA Regional Cancer Center	Norton	Virginia
United States	Norwalk Hospital	Norwalk	Connecticut
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	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	Mercy Hospital Oklahoma City	Oklahoma City	Oklahoma
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	Olathe Health Cancer Center	Olathe	Kansas
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	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	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	AdventHealth East Orlando	Orlando	Florida
United States	AdventHealth Medical Group Urology at Orlando	Orlando	Florida
United States	AdventHealth Orlando	Orlando	Florida
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	Ottawa Regional Hospital and Healthcare Center	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	University of Kansas Cancer Center-Overland Park	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	The Valley Hospital - Luckow Pavilion	Paramus	New Jersey
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	Cancer Center of Kansas - Parsons	Parsons	Kansas
United States	Memorial Hospital of Rhode Island	Pawtucket	Rhode Island
United States	Illinois CancerCare-Pekin	Pekin	Illinois
United States	OSF Saint Francis Radiation Oncology at Pekin	Pekin	Illinois
United States	Sacred Heart Hospital	Pensacola	Florida
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	Proctor Hospital	Peoria	Illinois
United States	Illinois CancerCare-Peru	Peru	Illinois
United States	Valley Radiation Oncology	Peru	Illinois
United States	McLaren Cancer Institute-Northern Michigan	Petoskey	Michigan
United States	Fox Chase Cancer Center	Philadelphia	Pennsylvania
United States	Jefferson Torresdale Hospital	Philadelphia	Pennsylvania
United States	Thomas Jefferson University Hospital	Philadelphia	Pennsylvania
United States	Mayo Clinic Hospital in Arizona	Phoenix	Arizona
United States	FirstHealth of the Carolinas-Moore Regional Hospital	Pinehurst	North Carolina
United States	Ascension Via Christi - Pittsburg	Pittsburg	Kansas
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	Penn Medicine Princeton Health	Plainsboro	New Jersey
United States	UM Sylvester Comprehensive Cancer Center at Plantation	Plantation	Florida
United States	Champlain Valley Physicians Hospital Medical Center	Plattsburgh	New York
United States	Michiana Hematology Oncology PC-Plymouth	Plymouth	Indiana
United States	Trinity Health Saint Joseph Mercy Oakland Hospital	Pontiac	Michigan
United States	Lake Huron Medical Center	Port Huron	Michigan
United States	Kaiser Permanente Northwest	Portland	Oregon
United States	Oregon Health and Science University	Portland	Oregon
United States	Providence Portland Medical Center	Portland	Oregon
United States	Providence Saint Vincent Medical Center	Portland	Oregon
United States	Portsmouth Regional Hospital	Portsmouth	New Hampshire
United States	Southern Ohio Medical Center	Portsmouth	Ohio
United States	Kootenai Clinic Cancer Services - Post Falls	Post Falls	Idaho
United States	Geisinger Cancer Services-Pottsville	Pottsville	Pennsylvania
United States	Harrison HealthPartners Hematology and Oncology-Poulsbo	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	Miriam Hospital	Providence	Rhode Island
United States	Rhode Island Hospital	Providence	Rhode Island
United States	Rocky Mountain Cancer Centers - Pueblo	Pueblo	Colorado
United States	Saint Mary Corwin Medical Center	Pueblo	Colorado
United States	Quincy Medical Group-Clinic	Quincy	Illinois
United States	Aurora Cancer Care-Racine	Racine	Wisconsin
United States	Northwest Hospital Center	Randallstown	Maryland
United States	Rapid City Regional Hospital	Rapid City	South Dakota
United States	Kaiser Permanente-Redwood City	Redwood City	California
United States	Corewell Health Reed City Hospital	Reed City	Michigan
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	Valley Health System Ridgewood Campus	Ridgewood	New Jersey
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	Carolina Blood and Cancer Care Associates PA	Rock Hill	South Carolina
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	Coborn Cancer Center at Saint Cloud Hospital	Saint Cloud	Minnesota
United States	Saint Cloud Hospital	Saint Cloud	Minnesota
United States	Saint Helena Hospital	Saint Helena	California
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	Salina Regional Health Center	Salina	Kansas
United States	TidalHealth Peninsula Regional	Salisbury	Maryland
United States	Cancer Therapy and Research Center at The UT Health Science Center at San Antonio	San Antonio	Texas
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 Zion	San Diego	California
United States	Naval Medical Center -San Diego	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	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	North Coast Cancer Care	Sandusky	Ohio
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	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	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	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	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	North Shore Medical Center	Skokie	Illinois
United States	Memorial Hospital of South Bend	South Bend	Indiana
United States	Michiana Hematology Oncology PC-South Bend	South Bend	Indiana
United States	Northern Indiana Cancer Research Consortium	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	D'Amour Center for Cancer Care	Springfield	Massachusetts
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	Blue Ridge Regional Hospital	Spruce Pine	North Carolina
United States	Geisinger Medical Group	State College	Pennsylvania
United States	Iredell Memorial Hospital	Statesville	North Carolina
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	Stony Brook University Medical Center	Stony Brook	New York
United States	Cleveland Clinic Cancer Center Strongsville	Strongsville	Ohio
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	Overlook Hospital	Summit	New Jersey
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	Northwest Medical Specialties PLLC	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	ProMedica Toledo Hospital/Russell J Ebeid Children's 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	University of Kansas Health System Saint Francis Campus	Topeka	Kansas
United States	Smilow Cancer Hospital-Torrington Care Center	Torrington	Connecticut
United States	Munson Medical Center	Traverse City	Michigan
United States	Claudia BR Herke MD PC	Troy	Michigan
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	Banner University Medical Center - Tucson	Tucson	Arizona
United States	University of Arizona Cancer Center-North Campus	Tucson	Arizona
United States	Natalie Warren Bryant Cancer Center at Saint Francis	Tulsa	Oklahoma
United States	Oklahoma Cancer Specialists and Research Institute-Tulsa	Tulsa	Oklahoma
United States	Warren Clinic Oncology-Tulsa	Tulsa	Oklahoma
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	Associates In Hematology Oncology PC-Upland	Upland	Pennsylvania
United States	Carle Cancer Center	Urbana	Illinois
United States	The Carle Foundation Hospital	Urbana	Illinois
United States	Faxton-Saint Luke's Healthcare	Utica	New York
United States	Kaiser Permanente Medical Center-Vacaville	Vacaville	California
United States	Northbay Cancer Center	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	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	South Pointe Hospital	Warrensville Heights	Ohio
United States	Northwestern Medicine Cancer Center Warrenville	Warrenville	Illinois
United States	MedStar Georgetown University Hospital	Washington	District of Columbia
United States	MedStar Washington Hospital Center	Washington	District of Columbia
United States	UPMC Washington Hospital Radiation Oncology	Washington	Pennsylvania
United States	Smilow Cancer Hospital-Waterbury Care Center	Waterbury	Connecticut
United States	Smilow Cancer Hospital Care Center - Waterford	Waterford	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	Chester County Hospital	West Chester	Pennsylvania
United States	University of Cincinnati Cancer Center-West Chester	West Chester	Ohio
United States	Lexington Medical Center	West Columbia	South Carolina
United States	Mercy Medical Center-West Lakes	West Des Moines	Iowa
United States	Veterans Affairs Connecticut Healthcare System-West Haven Campus	West Haven	Connecticut
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	Cleveland Clinic-Weston	Weston	Florida
United States	Diagnostic and Treatment Center	Weston	Wisconsin
United States	Marshfield Medical Center - Weston	Weston	Wisconsin
United States	Michiana Hematology Oncology PC-Westville	Westville	Indiana
United States	Valley Health System-Hematology/Oncology	Westwood	New Jersey
United States	SCL Health Lutheran Medical Center	Wheat Ridge	Colorado
United States	White River Junction Veteran Administration Medical Center	White River Junction	Vermont
United States	Presbyterian Intercommunity Hospital	Whittier	California
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	Shenandoah Oncology PC	Winchester	Virginia
United States	Winchester Hospital	Winchester	Massachusetts
United States	Cancer Center of Kansas - Winfield	Winfield	Kansas
United States	Southeast Clinical Oncology Research Consortium NCORP	Winston-Salem	North Carolina
United States	Wake Forest University Health Sciences	Winston-Salem	North Carolina
United States	AdventHealth Winter Park	Winter Park	Florida
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	Cleveland Clinic Wooster Family Health and Surgery Center	Wooster	Ohio
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	WellSpan Health-York Cancer Center	York	Pennsylvania
United States	WellSpan Health-York Hospital	York	Pennsylvania
United States	York Hospital	York	Maine
United States	Rush-Copley Healthcare Center	Yorkville	Illinois
United States	Yuma Regional Medical Center	Yuma	Arizona
United States	Genesis Healthcare System Cancer Care Center	Zanesville	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Geriatric Functional Status (Optional)	Assessed using the Older Americans' Resources and Services Multidimensional Functional Assessment Questionnaire, Activities of Daily Living, Medical Outcomes Study physical functioning, Karnofsky performance status rated by a health care professional, Karnofsky performance status rated by the patient, timed "Up and Go", and number of falls in the last six months.	Performed at 2.5 years after the last patient enrolled
Primary	Progression Free Survival (PFS)	The Kaplan-Meier method will be used to estimate the progression free survival distributions for each arm, with median estimates provided. Progression is defined as any one of the following: an increase in number of blood lymphocytes by >= 50% with >= 5000 B lymphocytes/mL in patients on Arm A or those on Arms 2 or 3 no longer receiving ibrutinib, >= 50% increase in the products of at least 2 lymph nodes on 2 consecutive determination 2 weeks apart, >= 50% increase in the size of the liver/spleen, transformation to a more aggressive histology, progression of any cytopenia (i.e. decrease of Hb levels > 2g/dL). Progression free survival time will be the time to either progression or death whichever occurs first.	Time from study entry to the time of documented disease progression or death. The analysis was event driven, performed at 2.5 years after the last patient enrolled;up to 4 years.
Secondary	Progression Free Survival (PFS) Rate at 2 Years	The Kaplan-Meier method will be used to estimate the rate of progression free survival at 2 years in each treatment arm. Progression is defined as any one of the following: an increase in number of blood lymphocytes by >= 50%, >= 50% increase in the products of at least 2 lymph nodes on 2 consecutive determination 2 weeks apart, >= 50% increase in the size of the liver/spleen, transformation to a more aggressive histology, progression of any cytopenia (i.e. decrease of Hb levels > 2g/dL). Progression free survival time will be the time to either progression or death whichever occurs first.	Time from study entry to the time of documented disease progression or death, assessed up to 2 years
Secondary	Overall Survival (OS) at 2 Years	The Kaplan-Meier method will be used to estimate the rate of overall survival at 2 years in each treatment arm. OS will be measured from the date of registration to the date of the event (i.e., death) or the date of last follow-up to evaluate that event. Patients who are event-free at their last follow-up evaluation will be censored at that time point.	From the date of registration to the date of death, assessed up to 2 years
Secondary	Duration of Response (DOR) (Complete Response [CR], CCR, Nodular Partial Response [nPR], Partial Response [PR], and PRL)	The Kaplan-Meier method will be used to estimate median DOR. DOR is the time from first objective status to progression or death. CR requires all of the following: absence of lymphadenopathy > 1.5 cm on physical exam/CT scan, no hepatomegaly/splenomegaly on physical exam, no clonal B-cells in the blood, Normal CBC, bone marrow aspirate & biopsy must be normocellular for age. PR requires >= 50% decrease in peripheral lymphocyte count from pre-treatment value, >= 50% reduction in lymphadenopathy, and/or = 50% reduction in splenomegaly/hepatomegaly. CR with exception of having bone marrow lymphoid CLL nodules will be considered a nodular PR (nPR). CR with exception of not having a bone marrow biopsy performed will be considered a clinical CR (CCR). PR with the exception of having less than a 50% reduction in peripheral lymphocyte count will be considered a PR except persistent lymphocytosis (PRL).	From the date of first response until progression or death, performed at 2.5 years after the last patient enrolled; up to 4 years.
Secondary	Percentage of Patients Achieving Any Response to Treatment (Overall Response Rate [ORR] [Complete Response [CR], CCR, Nodular Partial Response [nPR], Partial Response [PR], and PRL])	Complete response (CR) requires all of the following: absence of lymphadenopathy >1.5 cm on physical exam/CT scan, no hepatomegaly/splenomegaly on physical exam, no clonal B-cells in the blood, Normal CBC, bone marrow aspirate & biopsy must be normocellular for age. Partial response (PR) requires >= 50% decrease in peripheral lymphocyte count from pre-treatment value, >= 50% reduction in lymphadenopathy, and/or = 50% reduction in splenomegaly/hepatomegaly. CR with exception of having bone marrow lymphoid CLL nodules will be considered a nodular PR (nPR). CR with exception of not having a bone marrow biopsy performed will be considered a clinical CR (CCR). PR with the exception of having less than a 50% reduction in peripheral lymphocyte count will be considered a PR except persistent lymphocytosis (PRL).Overall response rate and corresponding exact binomial 95% CI provided.	Performed at 2.5 years after the last patient enrolled;up to 4 years.
Secondary	Percentage of Patients Achieving a Biopsy-proven Complete Response (CR)	Complete response (CR) requires all of the following: absence of lymphadenopathy > 1.5 cm on physical exam/CT scan, no hepatomegaly or splenomegaly on physical exam, no clonal B-cells in the blood, Normal CBC, bone marrow aspirate and biopsy must be normocellular for age. Complete response rate and corresponding exact binomial 95% confidence intervals provided.	Performed at 2.5 years after the last patient enrolled; up to 4 years.
Secondary	Percentage of Patients Achieving Complete (CR and CCR) or Nodular Partial Response (nPR)	Complete response (CR) requires all of the following: absence of lymphadenopathy > 1.5 cm on physical exam/CT scan, no hepatomegaly or splenomegaly on physical exam, no clonal B-cells in the blood, Normal CBC, bone marrow aspirate and biopsy must be normocellular for age. CR with exception of having bone marrow lymphoid CLL nodules will be considered a nodular PR (nPR). CR with exception of not having a bone marrow biopsy performed will be considered a clinical CR (CCR). Response rate and corresponding exact binomial 95% confidence intervals provided.	Performed at 2.5 years after the last patient enrolled; up to 4 years.
Secondary	Percentage of Patients Who Attain Minimal Residual Disease (MRD) Negative Status	Estimated using the number of patients who achieve minimal residual disease divided by the total number randomized to that treatment arm. Corresponding exact binomial 95% confidence intervals for MRD rates will be calculated.	Cycle 9 Day 1 Evaluation
Secondary	The Rate of Grade 3, 4, or 5 Treatment-related Non-hematologic Adverse Events (Toxicities)	The rate of grade 3, 4, or 5 treatment-related non-hematologic adverse events (toxicities) by arm; excludes adverse events occurring post-crossover for patients in Arm A	Performed at 2.5 years after the last patient enrolled; up to 4 years.

External Links

•   Data Available: Select individual patient-level data from this trial can be requested from the NCTN/NCORP Data Archive.