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

May 28, 2026 updated by: National Cancer Institute (NCI)

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)

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.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed 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 for a maximum of 10 years.

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.

Study Type

Interventional

Enrollment (Actual)

529

Phase

Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

United States
- Alabama
  - Birmingham, Alabama, United States, 35233
    - University of Alabama at Birmingham Cancer Center
- Alaska
  - Anchorage, Alaska, United States, 98508
    - Anchorage Associates in Radiation Medicine
  - Anchorage, Alaska, United States, 99508
    - Alaska Breast Care and Surgery LLC
  - Anchorage, Alaska, United States, 99508
    - Alaska Oncology and Hematology LLC
  - Anchorage, Alaska, United States, 99508
    - Alaska Women's Cancer Care
  - Anchorage, Alaska, United States, 99508
    - Anchorage Oncology Centre
  - Anchorage, Alaska, United States, 99508
    - Katmai Oncology Group
  - Anchorage, Alaska, United States, 99508
    - Providence Alaska Medical Center
  - Anchorage, Alaska, United States, 99504
    - Anchorage Radiation Therapy Center
  - Anchorage, Alaska, United States, 99508
    - Alaska Regional Hospital
  - Fairbanks, Alaska, United States, 99701
    - Fairbanks Memorial Hospital
- Arizona
  - Scottsdale, Arizona, United States, 85259
    - Mayo Clinic in Arizona
- Arkansas
  - Hot Springs, Arkansas, United States, 71913
    - CHI Saint Vincent Cancer Center Hot Springs
  - Jonesboro, Arkansas, United States, 72401
    - NEA Baptist Memorial Hospital and Fowler Family Cancer Center - Jonesboro
  - Little Rock, Arkansas, United States, 72205
    - University of Arkansas for Medical Sciences
- California
  - Anaheim, California, United States, 92806
    - Kaiser Permanente-Anaheim
  - Antioch, California, United States, 94531
    - Kaiser Permanente-Deer Valley Medical Center
  - Arroyo Grande, California, United States, 93420
    - PCR Oncology
  - Auburn, California, United States, 95602
    - Sutter Auburn Faith Hospital
  - Auburn, California, United States, 95603
    - Sutter Cancer Centers Radiation Oncology Services-Auburn
  - Baldwin Park, California, United States, 91706
    - Kaiser Permanente-Baldwin Park
  - Bellflower, California, United States, 90706
    - Kaiser Permanente-Bellflower
  - Berkeley, California, United States, 94704
    - Alta Bates Summit Medical Center-Herrick Campus
  - Burbank, California, United States, 91505
    - Providence Saint Joseph Medical Center/Disney Family Cancer Center
  - Burlingame, California, United States, 94010
    - Mills-Peninsula Medical Center
  - Cameron Park, California, United States, 95682
    - Sutter Cancer Centers Radiation Oncology Services-Cameron Park
  - Castro Valley, California, United States, 94546
    - Eden Hospital Medical Center
  - Chico, California, United States, 95973
    - Adventist Health Cancer Care Center Chico
  - Concord, California, United States, 94520
    - John Muir Medical Center-Concord
  - Davis, California, United States, 95616
    - Sutter Davis Hospital
  - Fontana, California, United States, 92335
    - Kaiser Permanente-Fontana
  - Fremont, California, United States, 94538
    - Kaiser Permanente-Fremont
  - Fresno, California, United States, 93720
    - Kaiser Permanente-Fresno
  - Greenbrae, California, United States, 94904
    - Marin Cancer Care Inc
  - Greenbrae, California, United States, 94904
    - Marin General Hospital
  - Harbor City, California, United States, 90710
    - Kaiser Permanente South Bay
  - Irvine, California, United States, 92618
    - Kaiser Permanente-Irvine
  - Los Angeles, California, United States, 90027
    - Kaiser Permanente Los Angeles Medical Center
  - Los Angeles, California, United States, 90034
    - Kaiser Permanente West Los Angeles
  - Modesto, California, United States, 95355
    - Memorial Medical Center
  - Modesto, California, United States, 95356
    - Kaiser Permanente-Modesto
  - Mountain View, California, United States, 94040
    - Palo Alto Medical Foundation-Camino Division
  - Mountain View, California, United States, 94040
    - Palo Alto Medical Foundation-Gynecologic Oncology
  - Novato, California, United States, 94945
    - Sutter Cancer Research Consortium
  - Oakland, California, United States, 94611
    - Kaiser Permanente-Oakland
  - Orange, California, United States, 92868
    - UC Irvine Health/Chao Family Comprehensive Cancer Center
  - Palo Alto, California, United States, 94304
    - Stanford Cancer Institute Palo Alto
  - Palo Alto, California, United States, 94301
    - Palo Alto Medical Foundation Health Care
  - Panorama City, California, United States, 91402
    - Kaiser Permanente - Panorama City
  - Redwood City, California, United States, 94063
    - Kaiser Permanente-Redwood City
  - Richmond, California, United States, 94801
    - Kaiser Permanente-Richmond
  - Riverside, California, United States, 92505
    - Kaiser Permanente-Riverside
  - Roseville, California, United States, 95661
    - Kaiser Permanente-Roseville
  - Roseville, California, United States, 95661
    - Sutter Cancer Centers Radiation Oncology Services-Roseville
  - Roseville, California, United States, 95661
    - Sutter Roseville Medical Center
  - Sacramento, California, United States, 95816
    - Sutter Medical Center Sacramento
  - Sacramento, California, United States, 95823
    - Kaiser Permanente-South Sacramento
  - Sacramento, California, United States, 95825
    - Kaiser Permanente Sacramento Medical Center
  - San Diego, California, United States, 92120
    - Kaiser Permanente-San Diego Zion
  - San Diego, California, United States, 92108
    - Kaiser Permanente-San Diego Mission
  - San Francisco, California, United States, 94115
    - Kaiser Permanente-San Francisco
  - San Francisco, California, United States, 94115
    - California Pacific Medical Center-Pacific Campus
  - San Jose, California, United States, 95119
    - Kaiser Permanente-Santa Teresa-San Jose
  - San Jose, California, United States, 95124
    - Stanford Cancer Center South Bay
  - San Leandro, California, United States, 94577
    - Kaiser Permanente San Leandro
  - San Luis Obispo, California, United States, 93401
    - Pacific Central Coast Health Center-San Luis Obispo
  - San Marcos, California, United States, 92078
    - Kaiser Permanente-San Marcos
  - San Rafael, California, United States, 94903
    - Kaiser Permanente-San Rafael
  - Santa Clara, California, United States, 95051
    - Kaiser Permanente Medical Center - Santa Clara
  - Santa Cruz, California, United States, 95065
    - Palo Alto Medical Foundation-Santa Cruz
  - Santa Rosa, California, United States, 95403
    - Kaiser Permanente-Santa Rosa
  - Santa Rosa, California, United States, 95403
    - Sutter Pacific Medical Foundation
  - South San Francisco, California, United States, 94080
    - Kaiser Permanente-South San Francisco
  - Stockton, California, United States, 95210
    - Kaiser Permanente-Stockton
  - Sunnyvale, California, United States, 94086
    - Palo Alto Medical Foundation-Sunnyvale
  - Vacaville, California, United States, 95688
    - Kaiser Permanente Medical Center-Vacaville
  - Vallejo, California, United States, 94589
    - Kaiser Permanente-Vallejo
  - Vallejo, California, United States, 94589
    - Sutter Solano Medical Center/Cancer Center
  - Walnut Creek, California, United States, 94596
    - Kaiser Permanente-Walnut Creek
  - Walnut Creek, California, United States, 94598
    - John Muir Medical Center-Walnut Creek
  - Woodland Hills, California, United States, 91367
    - Kaiser Permanente-Woodland Hills
- Colorado
  - Aurora, Colorado, United States, 80012
    - Rocky Mountain Cancer Centers-Aurora
  - Aurora, Colorado, United States, 80012
    - The Medical Center of Aurora
  - Boulder, Colorado, United States, 80303
    - Boulder Community Foothills Hospital
  - Boulder, Colorado, United States, 80304
    - Rocky Mountain Cancer Centers-Boulder
  - Colorado Springs, Colorado, United States, 80907
    - Penrose-Saint Francis Healthcare
  - Colorado Springs, Colorado, United States, 80907
    - Rocky Mountain Cancer Centers-Penrose
  - Denver, Colorado, United States, 80205
    - Kaiser Permanente-Franklin
  - Denver, Colorado, United States, 80218
    - Presbyterian - Saint Lukes Medical Center - Health One
  - Denver, Colorado, United States, 80220
    - Rose Medical Center
  - Denver, Colorado, United States, 80218
    - Rocky Mountain Cancer Centers-Midtown
  - Denver, Colorado, United States, 80220
    - Rocky Mountain Cancer Centers-Rose
  - Denver, Colorado, United States, 80204
    - Denver Health Medical Center
  - Denver, Colorado, United States, 80218
    - Colorado Blood Cancer Institute
  - Denver, Colorado, United States, 80222
    - Western States Cancer Research NCORP
  - Denver, Colorado, United States, 80206
    - National Jewish Health-Main Campus
  - Denver, Colorado, United States, 80218
    - Saint Joseph Hospital - Cancer Centers of Colorado
  - Denver, Colorado, United States, 80210
    - AdventHealth Porter
  - Durango, Colorado, United States, 81301
    - Mercy Medical Center
  - Durango, Colorado, United States, 81301
    - CommonSpirit Cancer Center Mercy
  - Englewood, Colorado, United States, 80113
    - Mountain Blue Cancer Care Center - Swedish
  - Englewood, Colorado, United States, 80113
    - Swedish Medical Center
  - Golden, Colorado, United States, 80401
    - Mountain Blue Cancer Care Center
  - Golden, Colorado, United States, 80401
    - National Jewish Health-Western Hematology Oncology
  - Greeley, Colorado, United States, 80631
    - Banner North Colorado Medical Center
  - Greenwood Village, Colorado, United States, 80111
    - Rocky Mountain Cancer Centers-Greenwood Village
  - Lafayette, Colorado, United States, 80026
    - Kaiser Permanente-Rock Creek
  - Lakewood, Colorado, United States, 80228
    - Rocky Mountain Cancer Centers-Lakewood
  - Lakewood, Colorado, United States, 80228
    - CommonSpirit Saint Anthony Hospital Cancer Center
  - Littleton, Colorado, United States, 80120
    - Rocky Mountain Cancer Centers-Littleton
  - Littleton, Colorado, United States, 80122
    - AdventHealth Littleton
  - Lone Tree, Colorado, United States, 80124
    - Kaiser Permanente-Lone Tree
  - Lone Tree, Colorado, United States, 80124
    - Sky Ridge Medical Center
  - Lone Tree, Colorado, United States, 80124
    - Rocky Mountain Cancer Centers-Sky Ridge
  - Longmont, Colorado, United States, 80501
    - Longmont United Hospital
  - Longmont, Colorado, United States, 80501
    - Rocky Mountain Cancer Centers-Longmont
  - Loveland, Colorado, United States, 80539
    - Banner North Colorado Medical Center - Loveland Campus
  - Parker, Colorado, United States, 80138
    - Rocky Mountain Cancer Centers-Parker
  - Parker, Colorado, United States, 80138
    - AdventHealth Parker
  - Pueblo, Colorado, United States, 81004
    - Saint Mary Corwin Medical Center
  - Pueblo, Colorado, United States, 81008
    - Rocky Mountain Cancer Centers - Pueblo
  - Thornton, Colorado, United States, 80260
    - Rocky Mountain Cancer Centers-Thornton
  - Wheat Ridge, Colorado, United States, 80401
    - Intermountain Health Lutheran Hospital
- Connecticut
  - Derby, Connecticut, United States, 06418
    - Smilow Cancer Hospital-Derby Care Center
  - Fairfield, Connecticut, United States, 06824
    - Smilow Cancer Hospital Care Center-Fairfield
  - Hartford, Connecticut, United States, 06105
    - Smilow Cancer Hospital Care Center at Saint Francis
  - Middletown, Connecticut, United States, 06457
    - Middlesex Hospital
  - New Haven, Connecticut, United States, 06520
    - Yale University
  - New Haven, Connecticut, United States, 06510
    - Smilow Cancer Center/Yale-New Haven Hospital
  - North Haven, Connecticut, United States, 06473
    - Yale-New Haven Hospital North Haven Medical Center
  - Orange, Connecticut, United States, 06477
    - Smilow Cancer Hospital-Orange Care Center
  - Torrington, Connecticut, United States, 06790
    - Smilow Cancer Hospital-Torrington Care Center
  - Trumbull, Connecticut, United States, 06611
    - Smilow Cancer Hospital Care Center-Trumbull
  - Waterbury, Connecticut, United States, 06708
    - Smilow Cancer Hospital-Waterbury Care Center
- Delaware
  - Lewes, Delaware, United States, 19958
    - Beebe Medical Center
  - Newark, Delaware, United States, 19713
    - Helen F Graham Cancer Center
  - Newark, Delaware, United States, 19713
    - Delaware Clinical and Laboratory Physicians PA
  - Newark, Delaware, United States, 19713
    - Medical Oncology Hematology Consultants PA
  - Newark, Delaware, United States, 19718
    - Christiana Care Health System-Christiana Hospital
  - Rehoboth Beach, Delaware, United States, 19971
    - Beebe Health Campus
  - Seaford, Delaware, United States, 19973
    - TidalHealth Nanticoke / Allen Cancer Center
  - Wilmington, Delaware, United States, 19801
    - Christiana Care Health System-Wilmington Hospital
- Florida
  - Jacksonville, Florida, United States, 32207
    - Baptist MD Anderson Cancer Center
  - Lakeland, Florida, United States, 33805
    - Lakeland Regional Health Hollis Cancer Center
  - Orlando, Florida, United States, 32806
    - Orlando Health Cancer Institute
- Georgia
  - Albany, Georgia, United States, 31701
    - Phoebe Putney Memorial Hospital
  - Atlanta, Georgia, United States, 30322
    - Emory University Hospital/Winship Cancer Institute
  - Columbus, Georgia, United States, 31904
    - John B Amos Cancer Center
  - Macon, Georgia, United States, 31201
    - Central Georgia Gynecologic Oncology
  - Macon, Georgia, United States, 31201
    - Atrium Health Navicent
  - Savannah, Georgia, United States, 31405
    - Lewis Cancer and Research Pavilion at Saint Joseph's/Candler
- Hawaii
  - Honolulu, Hawaii, United States, 96819
    - Kaiser Permanente Moanalua Medical Center
- Idaho
  - Boise, Idaho, United States, 83706
    - Saint Alphonsus Cancer Care Center-Boise
  - Boise, Idaho, United States, 83712
    - Saint Luke's Cancer Institute - Boise
  - Coeur d'Alene, Idaho, United States, 83814
    - Kootenai Health - Coeur d'Alene
  - Fruitland, Idaho, United States, 83619
    - Saint Luke's Cancer Institute - Fruitland
  - Meridian, Idaho, United States, 83642
    - Saint Luke's Cancer Institute - Meridian
  - Nampa, Idaho, United States, 83687
    - Saint Luke's Cancer Institute - Nampa
  - Post Falls, Idaho, United States, 83854
    - Kootenai Clinic Cancer Services - Post Falls
  - Sandpoint, Idaho, United States, 83864
    - Kootenai Clinic Cancer Services - Sandpoint
  - Twin Falls, Idaho, United States, 83301
    - Saint Luke's Cancer Institute - Twin Falls
- Illinois
  - Aurora, Illinois, United States, 60504
    - Rush-Copley Medical Center
  - Bloomington, Illinois, United States, 61704
    - Illinois CancerCare-Bloomington
  - Bloomington, Illinois, United States, 61701
    - OSF Saint Joseph Medical Center
  - Canton, Illinois, United States, 61520
    - Illinois CancerCare-Canton
  - Carbondale, Illinois, United States, 62902
    - Memorial Hospital of Carbondale
  - Carthage, Illinois, United States, 62321
    - Illinois CancerCare-Carthage
  - Centralia, Illinois, United States, 62801
    - Centralia Oncology Clinic
  - Chicago, Illinois, United States, 60611
    - Northwestern University
  - Chicago, Illinois, United States, 60637
    - University of Chicago Comprehensive Cancer Center
  - Danville, Illinois, United States, 61832
    - Carle at The Riverfront
  - Decatur, Illinois, United States, 62526
    - Decatur Memorial Hospital
  - Decatur, Illinois, United States, 62526
    - Cancer Care Specialists of Illinois - Decatur
  - Effingham, Illinois, United States, 62401
    - Crossroads Cancer Center
  - Effingham, Illinois, United States, 62401
    - Carle Physician Group-Effingham
  - Elk Grove Village, Illinois, United States, 60007
    - Ascension Alexian Brothers - Elk Grove Village
  - Eureka, Illinois, United States, 61530
    - Illinois CancerCare-Eureka
  - Evanston, Illinois, United States, 60201
    - NorthShore University HealthSystem-Evanston Hospital
  - Galesburg, Illinois, United States, 61401
    - Western Illinois Cancer Treatment Center
  - Galesburg, Illinois, United States, 61401
    - Illinois CancerCare-Galesburg
  - Geneva, Illinois, United States, 60134
    - Northwestern Medicine Cancer Center Delnor
  - Glenview, Illinois, United States, 60026
    - NorthShore University HealthSystem-Glenbrook Hospital
  - Highland Park, Illinois, United States, 60035
    - NorthShore University HealthSystem-Highland Park Hospital
  - Highland Park, Illinois, United States, 60035
    - Hematology Oncology Associates of Illinois-Highland Park
  - Joliet, Illinois, United States, 60435
    - Duly Health and Care Joliet
  - Kankakee, Illinois, United States, 60901
    - Presence Saint Mary's Hospital
  - Kewanee, Illinois, United States, 61443
    - Illinois CancerCare-Kewanee Clinic
  - Libertyville, Illinois, United States, 60048
    - AMG Libertyville - Oncology
  - Macomb, Illinois, United States, 61455
    - Illinois CancerCare-Macomb
  - Mattoon, Illinois, United States, 61938
    - Carle Physician Group-Mattoon/Charleston
  - Maywood, Illinois, United States, 60153
    - Loyola University Medical Center
  - Moline, Illinois, United States, 61265
    - Trinity Medical Center
  - Mount Vernon, Illinois, United States, 62864
    - SSM Health Good Samaritan
  - New Lenox, Illinois, United States, 60451
    - UC Comprehensive Cancer Center at Silver Cross
  - Niles, Illinois, United States, 60714
    - Illinois Cancer Specialists-Niles
  - Normal, Illinois, United States, 61761
    - Carle Cancer Institute Normal
  - O'Fallon, Illinois, United States, 62269
    - Cancer Care Center of O'Fallon
  - Oak Lawn, Illinois, United States, 60453-2699
    - Advocate Christ Medical Center
  - Ottawa, Illinois, United States, 61350
    - Illinois CancerCare-Ottawa Clinic
  - Ottawa, Illinois, United States, 61350
    - Radiation Oncology of Northern Illinois
  - Pekin, Illinois, United States, 61554
    - Illinois CancerCare-Pekin
  - Pekin, Illinois, United States, 61554
    - OSF Saint Francis Radiation Oncology at Pekin
  - Peoria, Illinois, United States, 61636
    - Methodist Medical Center of Illinois
  - Peoria, Illinois, United States, 61637
    - OSF Saint Francis Medical Center
  - Peoria, Illinois, United States, 61615
    - Illinois CancerCare-Peoria
  - Peoria, Illinois, United States, 61615
    - OSF Saint Francis Radiation Oncology at Peoria Cancer Center
  - Peru, Illinois, United States, 61354
    - Illinois CancerCare-Peru
  - Peru, Illinois, United States, 61354
    - Valley Radiation Oncology
  - Princeton, Illinois, United States, 61356
    - Illinois CancerCare-Princeton
  - Rockford, Illinois, United States, 61114
    - UW Health Carbone Cancer Center Rockford
  - Skokie, Illinois, United States, 60076
    - Hematology Oncology Associates of Illinois - Skokie
  - Skokie, Illinois, United States, 60076
    - North Shore Medical Center
  - Springfield, Illinois, United States, 62702
    - Southern Illinois University School of Medicine
  - Springfield, Illinois, United States, 62702
    - Springfield Clinic
  - Springfield, Illinois, United States, 62702
    - Central Illinois Hematology Oncology Center
  - Springfield, Illinois, United States, 62781
    - Springfield Memorial Hospital
  - Urbana, Illinois, United States, 61801
    - Carle Cancer Center
  - Urbana, Illinois, United States, 61801
    - The Carle Foundation Hospital
  - Warrenville, Illinois, United States, 60555
    - Northwestern Medicine Cancer Center Warrenville
  - Yorkville, Illinois, United States, 60560
    - Rush-Copley Healthcare Center
- Indiana
  - Anderson, Indiana, United States, 46016
    - Ascension Saint Vincent Anderson
  - Michigan City, Indiana, United States, 46360
    - Franciscan Saint Anthony Health-Michigan City
  - Michigan City, Indiana, United States, 46360
    - Woodland Cancer Care Center
  - Mishawaka, Indiana, United States, 46545
    - Memorial Regional Cancer Center Day Road
  - Richmond, Indiana, United States, 47374
    - Reid Health
  - South Bend, Indiana, United States, 46601
    - Memorial Hospital of South Bend
- Iowa
  - Ames, Iowa, United States, 50010
    - Mary Greeley Medical Center
  - Ames, Iowa, United States, 50010
    - McFarland Clinic - Ames
  - Boone, Iowa, United States, 50036
    - McFarland Clinic - Boone
  - Clive, Iowa, United States, 50325
    - Mercy Cancer Center-West Lakes
  - Clive, Iowa, United States, 50325
    - UI Health Care Mission Cancer and Blood - West Des Moines Clinic
  - Council Bluffs, Iowa, United States, 51503
    - Alegent Health Mercy Hospital
  - Creston, Iowa, United States, 50801
    - Greater Regional Medical Center
  - Des Moines, Iowa, United States, 50314
    - Mercy Medical Center - Des Moines
  - Des Moines, Iowa, United States, 50314
    - UI Health Care Mission Cancer and Blood - Laurel Clinic
  - Fort Dodge, Iowa, United States, 50501
    - McFarland Clinic - Trinity Cancer Center
  - Jefferson, Iowa, United States, 50129
    - McFarland Clinic - Jefferson
  - Marshalltown, Iowa, United States, 50158
    - McFarland Clinic - Marshalltown
  - Mason City, Iowa, United States, 50401
    - Mercy Medical Center - North Iowa
  - Sioux City, Iowa, United States, 51101
    - Siouxland Regional Cancer Center
  - Sioux City, Iowa, United States, 51102
    - Mercy Medical Center-Sioux City
  - Sioux City, Iowa, United States, 51104
    - Saint Luke's Regional Medical Center
  - Spencer, Iowa, United States, 51301
    - Abben Cancer Center
  - Waterloo, Iowa, United States, 50702
    - MercyOne Waterloo Cancer Center
  - West Des Moines, Iowa, United States, 50266
    - Mercy Medical Center-West Lakes
- Kansas
  - Chanute, Kansas, United States, 66720
    - Cancer Center of Kansas - Chanute
  - Dodge City, Kansas, United States, 67801
    - Cancer Center of Kansas - Dodge City
  - El Dorado, Kansas, United States, 67042
    - Cancer Center of Kansas - El Dorado
  - Fort Scott, Kansas, United States, 66701
    - Cancer Center of Kansas - Fort Scott
  - Independence, Kansas, United States, 67301
    - Cancer Center of Kansas-Independence
  - Kingman, Kansas, United States, 67068
    - Cancer Center of Kansas-Kingman
  - Lawrence, Kansas, United States, 66044
    - Lawrence Memorial Hospital
  - Lenexa, Kansas, United States, 66219
    - Kansas Institute of Medicine Cancer and Blood Center
  - Lenexa, Kansas, United States, 66219
    - Minimally Invasive Surgery Hospital
  - Liberal, Kansas, United States, 67905
    - Cancer Center of Kansas-Liberal
  - Newton, Kansas, United States, 67114
    - Cancer Center of Kansas - Newton
  - Overland Park, Kansas, United States, 66209
    - Menorah Medical Center
  - Overland Park, Kansas, United States, 66213
    - Saint Luke's South Hospital
  - Parsons, Kansas, United States, 67357
    - Cancer Center of Kansas - Parsons
  - Prairie Village, Kansas, United States, 66208
    - Kansas City NCI Community Oncology Research Program
  - Pratt, Kansas, United States, 67124
    - Cancer Center of Kansas - Pratt
  - Salina, Kansas, United States, 67401
    - Cancer Center of Kansas - Salina
  - Topeka, Kansas, United States, 66606
    - Cotton O'Neil Cancer Center / Stormont Vail Health
  - Wellington, Kansas, United States, 67152
    - Cancer Center of Kansas - Wellington
  - Wichita, Kansas, United States, 67214
    - Ascension Via Christi Hospitals Wichita
  - Wichita, Kansas, United States, 67208
    - Cancer Center of Kansas-Wichita Medical Arts Tower
  - Wichita, Kansas, United States, 67214
    - Cancer Center of Kansas - Wichita
  - Wichita, Kansas, United States, 67208
    - Associates In Womens Health
  - Winfield, Kansas, United States, 67156
    - Cancer Center of Kansas - Winfield
- Kentucky
  - Bardstown, Kentucky, United States, 40004
    - Flaget Memorial Hospital
  - Corbin, Kentucky, United States, 40701
    - Commonwealth Cancer Center-Corbin
  - Crestview Hills, Kentucky, United States, 41017
    - Oncology Hematology Care Inc-Crestview
  - Lexington, Kentucky, United States, 40504
    - Saint Joseph Radiation Oncology Resource Center
  - Lexington, Kentucky, United States, 40509
    - Saint Joseph Hospital East
  - Louisville, Kentucky, United States, 40202
    - Jewish Hospital
  - Louisville, Kentucky, United States, 40245
    - UofL Health Medical Center Northeast
  - Louisville, Kentucky, United States, 40215
    - Saints Mary and Elizabeth Hospital
  - Shepherdsville, Kentucky, United States, 40165
    - Jewish Hospital Medical Center South
- Louisiana
  - Baton Rouge, Louisiana, United States, 70809
    - Ochsner Health Center-Summa
  - Kenner, Louisiana, United States, 70065
    - Ochsner Medical Center Kenner
  - Monroe, Louisiana, United States, 71202
    - Ochsner LSU Health Monroe Medical Center
  - New Orleans, Louisiana, United States, 70121
    - Ochsner Medical Center Jefferson
  - Shreveport, Louisiana, United States, 71103
    - LSU Health Sciences Center at Shreveport
  - Shreveport, Louisiana, United States, 71105
    - CHRISTUS Highland Medical Center
- Maine
  - Augusta, Maine, United States, 04330
    - Harold Alfond Center for Cancer Care
  - Bangor, Maine, United States, 04401
    - Eastern Maine Medical Center
  - Brewer, Maine, United States, 04412
    - Lafayette Family Cancer Center-EMMC
  - Rockport, Maine, United States, 04856
    - Penobscot Bay Medical Center
- Maryland
  - Baltimore, Maryland, United States, 21201
    - University of Maryland/Greenebaum Cancer Center
  - Baltimore, Maryland, United States, 21229
    - Saint Agnes Hospital
- Massachusetts
  - Beverly, Massachusetts, United States, 01915
    - Beverly Hospital
  - Boston, Massachusetts, United States, 02111
    - Tufts Medical Center
  - Boston, Massachusetts, United States, 02215
    - Eastern Cooperative Oncology Group
  - Burlington, Massachusetts, United States, 01805
    - Lahey Hospital and Medical Center
  - Gloucester, Massachusetts, United States, 01930
    - Addison Gilbert Hospital
  - Springfield, Massachusetts, United States, 01199
    - Baystate Medical Center
  - Winchester, Massachusetts, United States, 01890
    - Beth Israel Deaconess Medical Center/Winchester Center for Cancer Care
  - Worcester, Massachusetts, United States, 01655
    - UMass Memorial Medical Center - University Campus
- Michigan
  - Adrian, Michigan, United States, 49221
    - Bixby Medical Center
  - Adrian, Michigan, United States, 49221
    - Hickman Cancer Center
  - Ann Arbor, Michigan, United States, 48106
    - Michigan Cancer Research Consortium NCORP
  - Ann Arbor, Michigan, United States, 48106
    - Trinity Health Saint Joseph Mercy Hospital Ann Arbor
  - Brownstown, Michigan, United States, 48183
    - Henry Ford Cancer Institute-Downriver
  - Clinton Township, Michigan, United States, 48038
    - Henry Ford Macomb Hospital-Clinton Township
  - Dearborn, Michigan, United States, 48126
    - Henry Ford Medical Center-Fairlane
  - Dearborn, Michigan, United States, 48124
    - Corewell Health Dearborn Hospital
  - Detroit, Michigan, United States, 48202
    - Henry Ford Hospital
  - Detroit, Michigan, United States, 48201
    - Wayne State University/Karmanos Cancer Institute
  - Detroit, Michigan, United States, 48236
    - Henry Ford Health Saint John Hospital
  - Escanaba, Michigan, United States, 49829
    - OSF Saint Francis Hospital and Medical Group
  - Farmington Hills, Michigan, United States, 48334
    - Weisberg Cancer Treatment Center
  - Farmington Hills, Michigan, United States, 48336
    - Corewell Health Farmington Hills Hospital
  - Flint, Michigan, United States, 48503
    - Hurley Medical Center
  - Flint, Michigan, United States, 48503
    - Genesys Hurley Cancer Institute
  - Grosse Pointe, Michigan, United States, 48230
    - William Beaumont Hospital-Grosse Pointe
  - Jackson, Michigan, United States, 49201
    - Allegiance Health
  - Kalamazoo, Michigan, United States, 49007
    - West Michigan Cancer Center
  - Lansing, Michigan, United States, 48912
    - University of Michigan Health - Sparrow Lansing
  - Livonia, Michigan, United States, 48154
    - Trinity Health Saint Mary Mercy Livonia Hospital
  - Monroe, Michigan, United States, 48162
    - Mercy Memorial Hospital
  - Monroe, Michigan, United States, 48162
    - Toledo Clinic Cancer Centers-Monroe
  - Monroe, Michigan, United States, 48162
    - Monroe Cancer Center
  - Novi, Michigan, United States, 48377
    - Henry Ford Medical Center-Columbus
  - Novi, Michigan, United States, 48374
    - Henry Ford Health Providence Novi Hospital
  - Pontiac, Michigan, United States, 48341
    - Trinity Health Saint Joseph Mercy Oakland Hospital
  - Port Huron, Michigan, United States, 48060
    - Lake Huron Medical Center
  - Roseville, Michigan, United States, 48066
    - Michigan Cancer Specialists
  - Royal Oak, Michigan, United States, 48073
    - Cancer Care Associates PC
  - Royal Oak, Michigan, United States, 48073
    - Comprehensive Medical Center PLLC
  - Royal Oak, Michigan, United States, 48073
    - Oakland Medical Group
  - Royal Oak, Michigan, United States, 48067
    - Oakland Colon Rectal Associates
  - Royal Oak, Michigan, United States, 48073
    - Hematology Oncology Consultants PC-Royal Oak
  - Royal Oak, Michigan, United States, 48073
    - Corewell Health William Beaumont University Hospital
  - Saginaw, Michigan, United States, 48601
    - MyMichigan Medical Center Saginaw
  - Southfield, Michigan, United States, 48075
    - Henry Ford Health Providence Southfield Hospital
  - Sterling Heights, Michigan, United States, 48312
    - Premier Hematology Oncology Care
  - Sterling Heights, Michigan, United States, 48314
    - Mitchell Folbe MD PC
  - Troy, Michigan, United States, 48084
    - Michigan Institute of Urology-Town Center
  - Troy, Michigan, United States, 48085
    - Claudia BR Herke MD PC
  - Troy, Michigan, United States, 48098
    - Hematology Oncology Consultants PC-Troy
  - Troy, Michigan, United States, 48085
    - Corewell Health Beaumont Troy Hospital
  - Warren, Michigan, United States, 48093
    - Henry Ford Health Warren Hospital
  - West Bloomfield, Michigan, United States, 48322
    - Henry Ford West Bloomfield Hospital
- Minnesota
  - Bemidji, Minnesota, United States, 56601
    - Sanford Joe Lueken Cancer Center
  - Brainerd, Minnesota, United States, 56401
    - Essentia Health Saint Joseph's Medical Center
  - Burnsville, Minnesota, United States, 55337
    - Fairview Ridges Hospital
  - Coon Rapids, Minnesota, United States, 55433
    - Mercy Hospital
  - Duluth, Minnesota, United States, 55805
    - Essentia Health Cancer Center
  - Duluth, Minnesota, United States, 55805
    - Essentia Health Saint Mary's Medical Center
  - Duluth, Minnesota, United States, 55805
    - Miller-Dwan Hospital
  - Edina, Minnesota, United States, 55435
    - Fairview Southdale Hospital
  - Fergus Falls, Minnesota, United States, 56537
    - Lake Region Healthcare Corporation-Cancer Care
  - Fridley, Minnesota, United States, 55432
    - Unity Hospital
  - Hutchinson, Minnesota, United States, 55350
    - Hutchinson Area Health Care
  - Maplewood, Minnesota, United States, 55109
    - Saint John's Hospital - Healtheast
  - Maplewood, Minnesota, United States, 55109
    - Minnesota Oncology Hematology PA-Maplewood
  - Minneapolis, Minnesota, United States, 55415
    - Hennepin County Medical Center
  - Minneapolis, Minnesota, United States, 55407
    - Abbott-Northwestern Hospital
  - Minneapolis, Minnesota, United States, 55454
    - Health Partners Inc
  - New Ulm, Minnesota, United States, 56073
    - New Ulm Medical Center
  - Robbinsdale, Minnesota, United States, 55422
    - North Memorial Medical Health Center
  - Rochester, Minnesota, United States, 55905
    - Mayo Clinic in Rochester
  - Saint Louis Park, Minnesota, United States, 55416
    - Park Nicollet Clinic - Saint Louis Park
  - Saint Louis Park, Minnesota, United States, 55416
    - Metro Minnesota Community Oncology Research Consortium
  - Saint Paul, Minnesota, United States, 55101
    - Regions Hospital
  - Saint Paul, Minnesota, United States, 55102
    - United Hospital
  - Shakopee, Minnesota, United States, 55379
    - Saint Francis Regional Medical Center
  - Stillwater, Minnesota, United States, 55082
    - Lakeview Hospital
  - Waconia, Minnesota, United States, 55387
    - Ridgeview Medical Center
  - Willmar, Minnesota, United States, 56201
    - Rice Memorial Hospital
  - Woodbury, Minnesota, United States, 55125
    - Minnesota Oncology Hematology PA-Woodbury
- Missouri
  - Bolivar, Missouri, United States, 65613
    - Central Care Cancer Center - Bolivar
  - Bonne Terre, Missouri, United States, 63628
    - Parkland Health Center-Bonne Terre
  - Branson, Missouri, United States, 65616
    - Cox Cancer Center Branson
  - Cape Girardeau, Missouri, United States, 63703
    - Saint Francis Medical Center
  - Cape Girardeau, Missouri, United States, 63703
    - Mercy Cancer Center - Cape Girardeau
  - City of Saint Peters, Missouri, United States, 63376
    - Siteman Cancer Center at Saint Peters Hospital
  - Creve Coeur, Missouri, United States, 63141
    - Siteman Cancer Center at West County Hospital
  - Independence, Missouri, United States, 64057
    - Centerpoint Medical Center LLC
  - Jefferson City, Missouri, United States, 65109
    - MU Health Care Goldschmidt Cancer Center
  - Joplin, Missouri, United States, 64804
    - Freeman Health System
  - Joplin, Missouri, United States, 64804
    - Mercy Hospital Joplin
  - Kansas City, Missouri, United States, 64111
    - Saint Luke's Hospital of Kansas City
  - Kansas City, Missouri, United States, 64132
    - Research Medical Center
  - Kansas City, Missouri, United States, 64118
    - Heartland Hematology and Oncology Associates Incorporated
  - Lee's Summit, Missouri, United States, 64086
    - Saint Luke's East - Lee's Summit
  - Liberty, Missouri, United States, 64068
    - Liberty Hospital
  - Rolla, Missouri, United States, 65401
    - Mercy Clinic-Rolla-Cancer and Hematology
  - Rolla, Missouri, United States, 65401
    - Phelps Health Delbert Day Cancer Institute
  - Saint Joseph, Missouri, United States, 64506
    - Heartland Regional Medical Center
  - Sainte Genevieve, Missouri, United States, 63670
    - Sainte Genevieve County Memorial Hospital
  - Springfield, Missouri, United States, 65807
    - CoxHealth South Hospital
  - Springfield, Missouri, United States, 65804
    - Mercy Hospital Springfield
  - St Louis, Missouri, United States, 63110
    - Washington University School of Medicine
  - St Louis, Missouri, United States, 63129
    - Siteman Cancer Center-South County
  - St Louis, Missouri, United States, 63131
    - Missouri Baptist Medical Center
  - St Louis, Missouri, United States, 63109
    - Mercy Infusion Center - Chippewa
  - St Louis, Missouri, United States, 63141
    - Mercy Hospital Saint Louis
  - Sullivan, Missouri, United States, 63080
    - Missouri Baptist Sullivan Hospital
  - Sunset Hills, Missouri, United States, 63127
    - BJC Outpatient Center at Sunset Hills
- Montana
  - Anaconda, Montana, United States, 59711
    - Community Hospital of Anaconda
  - Billings, Montana, United States, 59101
    - Billings Clinic Cancer Center
  - Billings, Montana, United States, 59101
    - Saint Vincent Healthcare
  - Billings, Montana, United States, 59102
    - Montana Cancer Consortium NCORP
  - Bozeman, Montana, United States, 59715
    - Bozeman Health Deaconess Hospital
  - Butte, Montana, United States, 59701
    - Saint James Community Hospital and Cancer Treatment Center
  - Great Falls, Montana, United States, 59405
    - Great Falls Clinic
  - Great Falls, Montana, United States, 59405
    - Benefis Sletten Cancer Institute
  - Helena, Montana, United States, 59601
    - Saint Peter's Community Hospital
  - Kalispell, Montana, United States, 59901
    - Logan Health Medical Center
  - Missoula, Montana, United States, 59802
    - Saint Patrick Hospital - Community Hospital
  - Missoula, Montana, United States, 59804
    - Community Medical Center
- Nebraska
  - Grand Island, Nebraska, United States, 68803
    - Nebraska Cancer Specialists/Oncology Hematology West PC
  - Kearney, Nebraska, United States, 68847
    - CHI Health Good Samaritan
  - Kearney, Nebraska, United States, 68845
    - Fred and Pamela Buffett Cancer Center - Kearney
  - Lincoln, Nebraska, United States, 68506
    - Nebraska Hematology and Oncology
  - Lincoln, Nebraska, United States, 68510
    - Nebraska Cancer Research Center
  - Lincoln, Nebraska, United States, 68510
    - Saint Elizabeth Regional Medical Center
  - Lincoln, Nebraska, United States, 68516
    - Cancer Partners of Nebraska
  - Norfolk, Nebraska, United States, 68701
    - Faith Regional Health Services Carson Cancer Center
  - North Platte, Nebraska, United States, 69101
    - Great Plains Health Callahan Cancer Center
  - Omaha, Nebraska, United States, 68198
    - University of Nebraska Medical Center
  - Omaha, Nebraska, United States, 68124
    - Alegent Health Bergan Mercy Medical Center
  - Omaha, Nebraska, United States, 68122
    - Alegent Health Immanuel Medical Center
  - Omaha, Nebraska, United States, 68130
    - Alegent Health Lakeside Hospital
  - Omaha, Nebraska, United States, 68131
    - Creighton University Medical Center
  - Omaha, Nebraska, United States, 68106
    - Missouri Valley Cancer Consortium
  - Omaha, Nebraska, United States, 68124
    - Nebraska Cancer Specialists - Omaha
  - Omaha, Nebraska, United States, 68130
    - Oncology Hematology West PC
  - Omaha, Nebraska, United States, 68122
    - Hematology and Oncology Consultants PC
  - Papillion, Nebraska, United States, 68046
    - Midlands Community Hospital
  - Scottsbluff, Nebraska, United States, 69361
    - Regional West Medical Center Cancer Center
- Nevada
  - Henderson, Nevada, United States, 89052
    - Comprehensive Cancer Centers of Nevada - Henderson
  - Henderson, Nevada, United States, 89052
    - Cancer and Blood Specialists-Henderson
  - Henderson, Nevada, United States, 89052
    - Las Vegas Cancer Center-Henderson
  - Henderson, Nevada, United States, 89074
    - Comprehensive Cancer Centers of Nevada-Southeast Henderson
  - Henderson, Nevada, United States, 89074
    - Oncology Las Vegas - Henderson
  - Las Vegas, Nevada, United States, 89144
    - Summerlin Hospital Medical Center
  - Las Vegas, Nevada, United States, 89106
    - Radiation Oncology Centers of Nevada Central
  - Las Vegas, Nevada, United States, 89119
    - Radiation Oncology Centers of Nevada Southeast
  - Las Vegas, Nevada, United States, 89128
    - Comprehensive Cancer Centers of Nevada - Northwest
  - Las Vegas, Nevada, United States, 89144
    - Comprehensive Cancer Centers of Nevada-Summerlin
  - Las Vegas, Nevada, United States, 89148
    - Comprehensive Cancer Centers of Nevada
  - Las Vegas, Nevada, United States, 89169
    - Comprehensive Cancer Centers of Nevada - Central Valley
  - Las Vegas, Nevada, United States, 89106
    - Cancer and Blood Specialists-Shadow
  - Las Vegas, Nevada, United States, 89109
    - HealthCare Partners Medical Group Oncology/Hematology-Maryland Parkway
  - Las Vegas, Nevada, United States, 89113
    - HealthCare Partners Medical Group Oncology/Hematology-San Martin
  - Las Vegas, Nevada, United States, 89121
    - Cancer Therapy and Integrative Medicine
  - Las Vegas, Nevada, United States, 89128
    - Cancer and Blood Specialists-Tenaya
  - Las Vegas, Nevada, United States, 89128
    - HealthCare Partners Medical Group Oncology/Hematology-Tenaya
  - Las Vegas, Nevada, United States, 89148-2405
    - Las Vegas Cancer Center-Medical Center
  - Las Vegas, Nevada, United States, 89149
    - HealthCare Partners Medical Group Oncology/Hematology-Centennial Hills
  - Las Vegas, Nevada, United States, 89120
    - Nevada Cancer Research Foundation NCORP
  - Las Vegas, Nevada, United States, 89128
    - Oncology Las Vegas - Tenaya
  - Las Vegas, Nevada, United States, 89183
    - OptumCare Cancer Care at Fort Apache
  - Reno, Nevada, United States, 89503
    - Saint Mary's Regional Medical Center
- New Hampshire
  - Dover, New Hampshire, United States, 03820
    - Wentworth-Douglass Hospital
- New Jersey
  - East Orange, New Jersey, United States, 07018-1095
    - Veterans Adminstration New Jersey Health Care System
  - Newark, New Jersey, United States, 07112
    - Newark Beth Israel Medical Center
- New Mexico
  - Albuquerque, New Mexico, United States, 87106
    - University of New Mexico Cancer Center
- New York
  - Albany, New York, United States, 12208
    - New York Oncology Hematology PC - Albany Medical Center
  - Auburn, New York, United States, 13021
    - Hematology Oncology Associates of Central New York-Auburn
  - Buffalo, New York, United States, 14263
    - Roswell Park Cancer Institute
  - Camillus, New York, United States, 13031
    - Hematology Oncology Associates of CNY at Camillus
  - Glens Falls, New York, United States, 12801
    - Glens Falls Hospital
  - Lake Success, New York, United States, 11042
    - Northwell Health/Center for Advanced Medicine
  - Liverpool, New York, United States, 13088
    - Hematology Oncology Associates of Central New York-Liverpool
  - Manhasset, New York, United States, 11030
    - North Shore University Hospital
  - Middletown, New York, United States, 10940
    - Garnet Health Medical Center
  - New Hyde Park, New York, United States, 11040
    - Long Island Jewish Medical Center
  - Rochester, New York, United States, 14642
    - University of Rochester
  - Rome, New York, United States, 13440
    - Hematology Oncology Associates of Central New York-Rome
  - Syracuse, New York, United States, 13210
    - State University of New York Upstate Medical University
- North Carolina
  - Asheville, North Carolina, United States, 28801
    - Mission Hospital
  - Asheville, North Carolina, United States, 28806
    - Messino Cancer Centers
  - Asheville, North Carolina, United States, 28803
    - AdventHealth Infusion Center Asheville
  - Clinton, North Carolina, United States, 28328
    - Southeastern Medical Oncology Center-Clinton
  - Clinton, North Carolina, United States, 28328
    - Sampson Radiation Oncology
  - Goldsboro, North Carolina, United States, 27534
    - Southeastern Medical Oncology Center-Goldsboro
  - Goldsboro, North Carolina, United States, 27534
    - Wayne Memorial Hospital
  - Goldsboro, North Carolina, United States, 27534
    - Wayne Radiation Oncology
  - Hendersonville, North Carolina, United States, 28791
    - Margaret R Pardee Memorial Hospital
  - Hendersonville, North Carolina, United States, 28792
    - AdventHealth Hendersonville
  - Jacksonville, North Carolina, United States, 28546
    - Southeastern Medical Oncology Center-Jacksonville
  - Jacksonville, North Carolina, United States, 28546
    - Onslow Memorial Hospital
  - Kinston, North Carolina, United States, 28501
    - ECU Health Oncology Kinston
  - Winston-Salem, North Carolina, United States, 27157
    - Wake Forest University Health Sciences
- North Dakota
  - Bismarck, North Dakota, United States, 58501
    - Sanford Bismarck Medical Center
  - Fargo, North Dakota, United States, 58122
    - Sanford Roger Maris Cancer Center
  - Fargo, North Dakota, United States, 58103
    - Essentia Health Cancer Center-South University Clinic
  - Fargo, North Dakota, United States, 58122
    - Sanford Broadway Medical Center
- Ohio
  - Akron, Ohio, United States, 44307
    - Cleveland Clinic Akron General
  - Beachwood, Ohio, United States, 44122
    - UHHS-Chagrin Highlands Medical Center
  - Belpre, Ohio, United States, 45714
    - Strecker Cancer Center-Belpre
  - Bowling Green, Ohio, United States, 43402
    - Toledo Clinic Cancer Centers-Bowling Green
  - Centerville, Ohio, United States, 45459
    - Miami Valley Hospital South
  - Centerville, Ohio, United States, 45459
    - Dayton Physicians LLC-Miami Valley South
  - Chardon, Ohio, United States, 44024
    - Geauga Hospital
  - Chillicothe, Ohio, United States, 45601
    - Adena Regional Medical Center
  - Cincinnati, Ohio, United States, 45219
    - University of Cincinnati Cancer Center-UC Medical Center
  - Cincinnati, Ohio, United States, 45220
    - Good Samaritan Hospital - Cincinnati
  - Cincinnati, Ohio, United States, 45242
    - Bethesda North Hospital
  - Cincinnati, Ohio, United States, 45242
    - Oncology Hematology Care Inc-Blue Ash
  - Cincinnati, Ohio, United States, 45202
    - Oncology Hematology Care Inc-Eden Park
  - Cincinnati, Ohio, United States, 45211
    - Oncology Hematology Care Inc-Mercy West
  - Cincinnati, Ohio, United States, 45230
    - Oncology Hematology Care Inc-Anderson
  - Cincinnati, Ohio, United States, 45236
    - Oncology Hematology Care Inc-Kenwood
  - Cincinnati, Ohio, United States, 45247
    - TriHealth Cancer Institute-Westside
  - Cincinnati, Ohio, United States, 45255
    - TriHealth Cancer Institute-Anderson
  - Cleveland, Ohio, United States, 44106
    - Case Western Reserve University
  - Cleveland, Ohio, United States, 44109
    - MetroHealth Medical Center
  - Columbus, Ohio, United States, 43214
    - Riverside Methodist Hospital
  - Columbus, Ohio, United States, 43219
    - The Mark H Zangmeister Center
  - Columbus, Ohio, United States, 43214
    - Columbus Oncology and Hematology Associates Inc
  - Columbus, Ohio, United States, 43228
    - Doctors Hospital
  - Columbus, Ohio, United States, 43213
    - Mount Carmel East Hospital
  - Columbus, Ohio, United States, 43215
    - Grant Medical Center
  - Columbus, Ohio, United States, 43222
    - Mount Carmel Health Center West
  - Columbus, Ohio, United States, 43215
    - Columbus NCI Community Oncology Research Program
  - Dayton, Ohio, United States, 45406
    - Good Samaritan Hospital - Dayton
  - Dayton, Ohio, United States, 45409
    - Miami Valley Hospital
  - Dayton, Ohio, United States, 45415
    - Miami Valley Hospital North
  - Dayton, Ohio, United States, 45459
    - Dayton NCI Community Oncology Research Program
  - Dayton, Ohio, United States, 45428
    - Dayton Veterans Affairs Medical Center
  - Dayton, Ohio, United States, 45415
    - Dayton Physician LLC - Englewood
  - Delaware, Ohio, United States, 43015
    - Delaware Health Center-Grady Cancer Center
  - Delaware, Ohio, United States, 43015
    - Delaware Radiation Oncology
  - Delaware, Ohio, United States, 43015
    - Grady Memorial Hospital
  - Elyria, Ohio, United States, 44035
    - Mercy Cancer Center-Elyria
  - Fairfield, Ohio, United States, 45014
    - Oncology Hematology Care Inc-Healthplex
  - Findlay, Ohio, United States, 45840
    - Blanchard Valley Hospital
  - Findlay, Ohio, United States, 45840
    - Armes Family Cancer Center
  - Findlay, Ohio, United States, 45840
    - Orion Cancer Care
  - Franklin, Ohio, United States, 45005-1066
    - Atrium Medical Center-Middletown Regional Hospital
  - Franklin, Ohio, United States, 45005
    - Dayton Physicians LLC-Atrium
  - Greenville, Ohio, United States, 45331
    - Wayne Hospital
  - Greenville, Ohio, United States, 45331
    - Dayton Physicians LLC-Wayne
  - Kettering, Ohio, United States, 45429
    - Kettering Medical Center
  - Kettering, Ohio, United States, 45409
    - Greater Dayton Cancer Center
  - Lancaster, Ohio, United States, 43130
    - Fairfield Medical Center
  - Lancaster, Ohio, United States, 43130
    - Lancaster Radiation Oncology
  - Lima, Ohio, United States, 45804
    - Lima Memorial Hospital
  - Mansfield, Ohio, United States, 44903
    - OhioHealth Mansfield Hospital
  - Marietta, Ohio, United States, 45750
    - Marietta Memorial Hospital
  - Marion, Ohio, United States, 43302
    - OhioHealth Marion General Hospital
  - Maumee, Ohio, United States, 43537
    - Toledo Clinic Cancer Centers-Maumee
  - Maumee, Ohio, United States, 43537
    - Toledo Radiation Oncology at Northwest Ohio Onocolgy Center
  - Mayfield Heights, Ohio, United States, 44124
    - UH Seidman Cancer Center at Landerbrook Health Center
  - Mentor, Ohio, United States, 44060
    - UH Seidman Cancer Center at Lake Health Mentor Campus
  - Middleburg Heights, Ohio, United States, 44130
    - UH Seidman Cancer Center at Southwest General Hospital
  - Middletown, Ohio, United States, 45042
    - Dayton Physicians LLC-Signal Point
  - Mount Vernon, Ohio, United States, 43050
    - Knox Community Hospital
  - Newark, Ohio, United States, 43055
    - Licking Memorial Hospital
  - Newark, Ohio, United States, 43055
    - Newark Radiation Oncology
  - Oregon, Ohio, United States, 43616
    - Saint Charles Hospital
  - Oregon, Ohio, United States, 43616
    - Toledo Clinic Cancer Centers-Oregon
  - Parma, Ohio, United States, 44129
    - University Hospitals Parma Medical Center
  - Portsmouth, Ohio, United States, 45662
    - Southern Ohio Medical Center
  - Sidney, Ohio, United States, 45365
    - Dayton Physicians LLC-Wilson
  - Springfield, Ohio, United States, 45504
    - Springfield Regional Cancer Center
  - Springfield, Ohio, United States, 45504
    - Springfield Regional Medical Center
  - Sylvania, Ohio, United States, 43560
    - ProMedica Flower Hospital
  - Tiffin, Ohio, United States, 44883
    - Mercy Hospital of Tiffin
  - Toledo, Ohio, United States, 43623
    - Mercy Health - Saint Anne Hospital
  - Toledo, Ohio, United States, 43623
    - Toledo Clinic Cancer Centers-Toledo
  - Toledo, Ohio, United States, 43614
    - University of Toledo
  - Toledo, Ohio, United States, 43617
    - Toledo Community Hospital Oncology Program CCOP
  - Toledo, Ohio, United States, 43608
    - Mercy Health - Saint Vincent Hospital
  - Troy, Ohio, United States, 45373
    - Upper Valley Medical Center
  - Troy, Ohio, United States, 45373
    - Dayton Physicians LLC - Troy
  - Wadsworth, Ohio, United States, 44281
    - University Hospitals Sharon Health Center
  - Wauseon, Ohio, United States, 43567
    - Fulton County Health Center
  - West Chester, Ohio, United States, 45069
    - University of Cincinnati Cancer Center-West Chester
  - Westerville, Ohio, United States, 43081
    - Saint Ann's Hospital
  - Westlake, Ohio, United States, 44145
    - UH Seidman Cancer Center at Saint John Medical Center
  - Wright-Patterson Air Force Base, Ohio, United States, 45433
    - Wright-Patterson Medical Center
  - Zanesville, Ohio, United States, 43701
    - Genesis Healthcare System Cancer Care Center
- Oklahoma
  - Lawton, Oklahoma, United States, 73505
    - Cancer Centers of Southwest Oklahoma Research
  - Oklahoma City, Oklahoma, United States, 73104
    - University of Oklahoma Health Sciences Center
- Oregon
  - Bend, Oregon, United States, 97701
    - Saint Charles Health System
  - Clackamas, Oregon, United States, 97015
    - Clackamas Radiation Oncology Center
  - Clackamas, Oregon, United States, 97015
    - Providence Cancer Institute Clackamas Clinic
  - Coos Bay, Oregon, United States, 97420
    - Bay Area Hospital
  - Milwaukie, Oregon, United States, 97222
    - Providence Milwaukie Hospital
  - Newberg, Oregon, United States, 97132
    - Providence Newberg Medical Center
  - Oregon City, Oregon, United States, 97045
    - Providence Willamette Falls Medical Center
  - Portland, Oregon, United States, 97213
    - Providence Portland Medical Center
  - Portland, Oregon, United States, 97225
    - Providence Saint Vincent Medical Center
  - Portland, Oregon, United States, 97227
    - Kaiser Permanente Northwest
- Pennsylvania
  - Allentown, Pennsylvania, United States, 18103
    - Lehigh Valley Hospital-Cedar Crest
  - Beaver, Pennsylvania, United States, 15009
    - UPMC-Heritage Valley Health System Beaver
  - Bethlehem, Pennsylvania, United States, 18017
    - Lehigh Valley Hospital - Muhlenberg
  - Bryn Mawr, Pennsylvania, United States, 19010
    - Bryn Mawr Hospital
  - Chadds Ford, Pennsylvania, United States, 19317
    - Christiana Care Health System-Concord Health Center
  - Danville, Pennsylvania, United States, 17822
    - Geisinger Medical Center
  - Erie, Pennsylvania, United States, 16505
    - UPMC Hillman Cancer Center Erie
  - Greensburg, Pennsylvania, United States, 15601
    - UPMC Cancer Centers - Arnold Palmer Pavilion
  - Hazleton, Pennsylvania, United States, 18201
    - Geisinger Medical Center-Cancer Center Hazleton
  - Hershey, Pennsylvania, United States, 17033-0850
    - Penn State Milton S Hershey Medical Center
  - Johnstown, Pennsylvania, United States, 15901
    - UPMC-Johnstown/John P. Murtha Regional Cancer Center
  - Lancaster, Pennsylvania, United States, 17602
    - Lancaster General Hospital
  - Lewisburg, Pennsylvania, United States, 17837
    - Geisinger Medical Oncology-Lewisburg
  - Lewistown, Pennsylvania, United States, 17044
    - Lewistown Hospital
  - McKeesport, Pennsylvania, United States, 15132
    - UPMC Cancer Center at UPMC McKeesport
  - Media, Pennsylvania, United States, 19063
    - Riddle Memorial Hospital
  - Moon Township, Pennsylvania, United States, 15108
    - UPMC Hillman Cancer Center in Coraopolis
  - Paoli, Pennsylvania, United States, 19301
    - Paoli Memorial Hospital
  - Philadelphia, Pennsylvania, United States, 19107
    - Thomas Jefferson University Hospital
  - Philadelphia, Pennsylvania, United States, 19104
    - University of Pennsylvania/Abramson Cancer Center
  - Philadelphia, Pennsylvania, United States, 19102
    - Drexel University School of Medicine
  - Pittsburgh, Pennsylvania, United States, 15213
    - UPMC-Magee Womens Hospital
  - Pittsburgh, Pennsylvania, United States, 15232
    - University of Pittsburgh Cancer Institute (UPCI)
  - Pittsburgh, Pennsylvania, United States, 15232
    - UPMC-Shadyside Hospital
  - Pittsburgh, Pennsylvania, United States, 15213
    - UPMC-Presbyterian Hospital
  - Pittsburgh, Pennsylvania, United States, 15215
    - UPMC-Saint Margaret
  - Pittsburgh, Pennsylvania, United States, 15236
    - UPMC Jefferson Regional Radiation Oncology
  - Pittsburgh, Pennsylvania, United States, 15237
    - UPMC-Passavant Hospital
  - Pittsburgh, Pennsylvania, United States, 15243
    - UPMC-Saint Clair Hospital Cancer Center
  - Pottstown, Pennsylvania, United States, 19464
    - Pottstown Hospital
  - Pottsville, Pennsylvania, United States, 17901
    - Geisinger Cancer Services-Pottsville
  - Scranton, Pennsylvania, United States, 18508
    - Hematology and Oncology Associates of North East Pennsylvania
  - Seneca, Pennsylvania, United States, 16346
    - UPMC Cancer Center at UPMC Northwest
  - State College, Pennsylvania, United States, 16801
    - Geisinger Medical Group
  - Uniontown, Pennsylvania, United States, 15401
    - UPMC Uniontown Hospital Radiation Oncology
  - Washington, Pennsylvania, United States, 15301
    - UPMC Washington Hospital Radiation Oncology
  - West Reading, Pennsylvania, United States, 19611
    - Reading Hospital
  - Wilkes-Barre, Pennsylvania, United States, 18711
    - Geisinger Wyoming Valley/Henry Cancer Center
  - Williamsport, Pennsylvania, United States, 17701
    - UPMC Susquehanna
  - Wynnewood, Pennsylvania, United States, 19096
    - Lankenau Medical Center
- South Carolina
  - Boiling Springs, South Carolina, United States, 29316
    - Prisma Health Cancer Institute - Spartanburg
  - Easley, South Carolina, United States, 29640
    - Prisma Health Cancer Institute - Easley
  - Gaffney, South Carolina, United States, 29341
    - Gibbs Cancer Center-Gaffney
  - Greenville, South Carolina, United States, 29605
    - Prisma Health Cancer Institute - Faris
  - Greenville, South Carolina, United States, 29607
    - Saint Francis Cancer Center
  - Greenville, South Carolina, United States, 29615
    - Prisma Health Cancer Institute - Eastside
  - Greenville, South Carolina, United States, 29605
    - Prisma Health Cancer Institute - Butternut
  - Greenville, South Carolina, United States, 29601
    - Saint Francis Hospital
  - Greenville, South Carolina, United States, 29605
    - Prisma Health Greenville Memorial Hospital
  - Greenville, South Carolina, United States, 29601
    - Greenville Health System Cancer Institute-Andrews
  - Greer, South Carolina, United States, 29650
    - Prisma Health Cancer Institute - Greer
  - Greer, South Carolina, United States, 29651
    - Gibbs Cancer Center-Pelham
  - Seneca, South Carolina, United States, 29672
    - Prisma Health Cancer Institute - Seneca
  - Spartanburg, South Carolina, United States, 29303
    - Spartanburg Medical Center
  - Union, South Carolina, United States, 29379
    - SMC Center for Hematology Oncology Union
- South Dakota
  - Rapid City, South Dakota, United States, 57701
    - Rapid City Regional Hospital
  - Sioux Falls, South Dakota, United States, 57105
    - Avera Cancer Institute
  - Sioux Falls, South Dakota, United States, 57117-5134
    - Sanford USD Medical Center - Sioux Falls
  - Sioux Falls, South Dakota, United States, 57104
    - Sanford Cancer Center Oncology Clinic
- Tennessee
  - Bristol, Tennessee, United States, 37620
    - Bristol Regional Medical Center
  - Chattanooga, Tennessee, United States, 37404
    - Memorial Hospital
  - Hixson, Tennessee, United States, 37343
    - Pulmonary Medicine Center of Chattanooga-Hixson
  - Johnson City, Tennessee, United States, 37604
    - Wellmont Medical Associates Oncology and Hematology-Johnson City
  - Kingsport, Tennessee, United States, 37660
    - Ballad Health Cancer Care - Kingsport
  - Kingsport, Tennessee, United States, 37660
    - Wellmont Holston Valley Hospital and Medical Center
  - Nashville, Tennessee, United States, 37208
    - Meharry Medical College
  - Ooltewah, Tennessee, United States, 37363
    - Memorial GYN Plus
- Texas
  - Amarillo, Texas, United States, 79106
    - The Don and Sybil Harrington Cancer Center
  - Dallas, Texas, United States, 75235
    - Parkland Memorial Hospital
  - Dallas, Texas, United States, 75390
    - UT Southwestern/Simmons Cancer Center-Dallas
  - Lubbock, Texas, United States, 79410
    - Covenant Medical Center-Lakeside
  - San Antonio, Texas, United States, 78229
    - University Hospital
  - San Antonio, Texas, United States, 78229
    - University of Texas Health Science Center at San Antonio
- Vermont
  - Berlin Corners, Vermont, United States, 05602
    - Central Vermont Medical Center/National Life Cancer Treatment
  - Burlington, Vermont, United States, 05401
    - University of Vermont Medical Center
  - Burlington, Vermont, United States, 05405
    - University of Vermont and State Agricultural College
- Virginia
  - Danville, Virginia, United States, 24541
    - Danville Regional Medical Center
  - Fredericksburg, Virginia, United States, 22401
    - Fredericksburg Oncology Inc
  - Fredericksburg, Virginia, United States, 22408
    - Hematology Oncology Associates of Fredericksburg Inc
  - Lynchburg, Virginia, United States, 24501
    - Centra Alan B Pearson Regional Cancer Center
  - Martinsville, Virginia, United States, 24112
    - Sovah Health Martinsville
  - Norton, Virginia, United States, 24273
    - Ballad Health Cancer Care - Norton
  - Richmond, Virginia, United States, 23229
    - Virginia Cancer Institute
  - Richmond, Virginia, United States, 23298
    - VCU Massey Comprehensive Cancer Center
  - South Hill, Virginia, United States, 23970
    - VCU Community Memorial Health Center
- Washington
  - Aberdeen, Washington, United States, 98520
    - Providence Regional Cancer System-Aberdeen
  - Anacortes, Washington, United States, 98221
    - Cancer Care Center at Island Hospital
  - Auburn, Washington, United States, 98001
    - MultiCare Auburn Medical Center
  - Bainbridge Island, Washington, United States, 98110
    - Virginia Mason Bainbridge Island Medical Center
  - Bellevue, Washington, United States, 98004
    - Overlake Medical Center
  - Bellevue, Washington, United States, 98005
    - Swedish Cancer Institute-Eastside Oncology Hematology
  - Bellingham, Washington, United States, 98225
    - PeaceHealth Saint Joseph Medical Center
  - Burien, Washington, United States, 98166
    - Highline Medical Center-Main Campus
  - Centralia, Washington, United States, 98531
    - Providence Regional Cancer System-Centralia
  - Edmonds, Washington, United States, 98026
    - Swedish Cancer Institute-Edmonds
  - Enumclaw, Washington, United States, 98022
    - Saint Elizabeth Hospital
  - Everett, Washington, United States, 98201
    - Providence Regional Cancer Partnership
  - Federal Way, Washington, United States, 98002
    - Virginia Mason Federal Way Medical Center
  - Federal Way, Washington, United States, 98003
    - Saint Francis Hospital
  - Gig Harbor, Washington, United States, 98332
    - Tacoma/Valley Radiation Oncology Centers-Gig Harbor
  - Gig Harbor, Washington, United States, 98335
    - MultiCare Gig Harbor Medical Park
  - Issaquah, Washington, United States, 98029
    - Swedish Cancer Institute-Issaquah
  - Kennewick, Washington, United States, 99336
    - Northwest Cancer Clinic
  - Lacey, Washington, United States, 98503
    - Providence Regional Cancer System-Lacey
  - Lakewood, Washington, United States, 98499
    - Saint Clare Hospital
  - Longview, Washington, United States, 98632
    - PeaceHealth Saint John Medical Center
  - Lynnwood, Washington, United States, 98036
    - Virginia Mason Lynnwood Medical Center
  - Port Townsend, Washington, United States, 98368
    - Jefferson Healthcare
  - Poulsbo, Washington, United States, 98370
    - Harrison HealthPartners Hematology and Oncology-Poulsbo
  - Poulsbo, Washington, United States, 98370
    - Peninsula Cancer Center
  - Puyallup, Washington, United States, 98372
    - MultiCare Good Samaritan Hospital
  - Puyallup, Washington, United States, 98372
    - Tacoma/Valley Radiation Oncology Centers-Puyallup
  - Seattle, Washington, United States, 98101
    - Virginia Mason Medical Center
  - Seattle, Washington, United States, 98107
    - Swedish Medical Center-Ballard Campus
  - Seattle, Washington, United States, 98122
    - Swedish Medical Center-First Hill
  - Seattle, Washington, United States, 98195
    - University of Washington Medical Center - Montlake
  - Seattle, Washington, United States, 98112
    - Kaiser Permanente Washington
  - Seattle, Washington, United States, 98104
    - Minor and James Medical PLLC
  - Seattle, Washington, United States, 98104
    - Pacific Gynecology Specialists
  - Seattle, Washington, United States, 98109
    - Fred Hutchinson Cancer Center
  - Shelton, Washington, United States, 98584
    - Providence Regional Cancer System-Shelton
  - Silverdale, Washington, United States, 98383
    - Saint Joseph Medical Center Hematology and Oncology - Silverdale
  - Spokane, Washington, United States, 99218
    - Evergreen Hematology and Oncology PS
  - Spokane, Washington, United States, 99204
    - MultiCare Deaconess Cancer and Blood Specialty Center - Downtown
  - Spokane Valley, Washington, United States, 99216
    - MultiCare Deaconess Cancer and Blood Specialty Center - Valley
  - Tacoma, Washington, United States, 98405
    - Northwest Medical Specialties PLLC
  - Tacoma, Washington, United States, 98405
    - MultiCare Tacoma General Hospital
  - Tacoma, Washington, United States, 98405
    - Tacoma/Valley Radiation Oncology Centers-Saint Joe's
  - Tacoma, Washington, United States, 97405
    - Tacoma/Valley Radiation Oncology Centers-Jackson Hall
  - Tacoma, Washington, United States, 98405
    - Franciscan Research Center-Northwest Medical Plaza
  - Tacoma, Washington, United States, 98405
    - Northwest NCI Community Oncology Research Program
  - Vancouver, Washington, United States, 98664
    - PeaceHealth Southwest Medical Center
  - Walla Walla, Washington, United States, 99362
    - Providence Saint Mary Regional Cancer Center
  - Yakima, Washington, United States, 98902
    - North Star Lodge Cancer Center at Yakima Valley Memorial Hospital
  - Yelm, Washington, United States, 98597
    - Providence Regional Cancer System-Yelm
- West Virginia
  - Bridgeport, West Virginia, United States, 26330
    - United Hospital Center
  - Martinsburg, West Virginia, United States, 25401
    - WVUH-Berkely Medical Center
  - Morgantown, West Virginia, United States, 26506
    - West Virginia University Healthcare
  - Parkersburg, West Virginia, United States, 26101
    - Camden Clark Medical Center
- Wisconsin
  - Antigo, Wisconsin, United States, 54409
    - Langlade Hospital and Cancer Center
  - Burlington, Wisconsin, United States, 53105
    - Aurora Cancer Care-Southern Lakes VLCC
  - Chippewa Falls, Wisconsin, United States, 54729
    - Marshfield Clinic-Chippewa Center
  - Eau Claire, Wisconsin, United States, 54701
    - HSHS Sacred Heart Hospital
  - Eau Claire, Wisconsin, United States, 54701
    - Marshfield Clinic Cancer Center at Sacred Heart
  - Fond du Lac, Wisconsin, United States, 54937
    - Aurora Health Center-Fond du Lac
  - Germantown, Wisconsin, United States, 53022
    - Aurora Health Care Germantown Health Center
  - Grafton, Wisconsin, United States, 53024
    - Aurora Cancer Care-Grafton
  - Green Bay, Wisconsin, United States, 54311
    - Aurora BayCare Medical Center
  - Green Bay, Wisconsin, United States, 54301
    - Saint Vincent Hospital Cancer Center Green Bay
  - Green Bay, Wisconsin, United States, 54303
    - Saint Vincent Hospital Cancer Center at Saint Mary's
  - Green Bay, Wisconsin, United States, 54301
    - Bellin Memorial Hospital
  - Green Bay, Wisconsin, United States, 54301-3526
    - Green Bay Oncology at Saint Vincent Hospital
  - Janesville, Wisconsin, United States, 53548
    - Mercyhealth Hospital and Cancer Center - Janesville
  - Kenosha, Wisconsin, United States, 53142
    - Aurora Cancer Care-Kenosha South
  - La Crosse, Wisconsin, United States, 54601
    - Gundersen Lutheran Medical Center
  - Ladysmith, Wisconsin, United States, 54848
    - Marshfield Medical Center - Ladysmith
  - Manitowoc, Wisconsin, United States, 54221
    - Holy Family Memorial Hospital
  - Marinette, Wisconsin, United States, 54143
    - Aurora Bay Area Medical Group-Marinette
  - Marshfield, Wisconsin, United States, 54449
    - Marshfield Medical Center-Marshfield
  - Marshfield, Wisconsin, United States, 54449
    - Marshfield Medical Center
  - Milwaukee, Wisconsin, United States, 53226
    - Medical College of Wisconsin
  - Milwaukee, Wisconsin, United States, 53209
    - Aurora Cancer Care-Milwaukee
  - Milwaukee, Wisconsin, United States, 53215
    - Aurora Saint Luke's Medical Center
  - Milwaukee, Wisconsin, United States, 53233
    - Aurora Sinai Medical Center
  - Minocqua, Wisconsin, United States, 54548
    - Marshfield Medical Center - Minocqua
  - Mukwonago, Wisconsin, United States, 53149
    - ProHealth D N Greenwald Center
  - New Richmond, Wisconsin, United States, 54017
    - Cancer Center of Western Wisconsin
  - Oconomowoc, Wisconsin, United States, 53066
    - ProHealth Oconomowoc Memorial Hospital
  - Oconto Falls, Wisconsin, United States, 54154
    - Saint Vincent Hospital Cancer Center at Oconto Falls
  - Oshkosh, Wisconsin, United States, 54904
    - Vince Lombardi Cancer Clinic - Oshkosh
  - Racine, Wisconsin, United States, 53406
    - Aurora Cancer Care-Racine
  - Rhinelander, Wisconsin, United States, 54501
    - Saint Mary's Hospital
  - Rhinelander, Wisconsin, United States, 54501
    - Aspirus Cancer Care - James Beck Cancer Center
  - Rice Lake, Wisconsin, United States, 54868
    - Marshfield Medical Center-Rice Lake
  - Sheboygan, Wisconsin, United States, 53081
    - Vince Lombardi Cancer Clinic-Sheboygan
  - Sheboygan, Wisconsin, United States, 53081
    - HSHS Saint Nicholas Hospital
  - Stevens Point, Wisconsin, United States, 54481
    - Aspirus Cancer Care - Stevens Point
  - Summit, Wisconsin, United States, 53066
    - Aurora Medical Center in Summit
  - Two Rivers, Wisconsin, United States, 54241
    - Vince Lombardi Cancer Clinic-Two Rivers
  - Waukesha, Wisconsin, United States, 53188
    - UW Cancer Center at ProHealth Care
  - Waukesha, Wisconsin, United States, 53188
    - ProHealth Waukesha Memorial Hospital
  - Waukesha, Wisconsin, United States, 53188
    - Aurora Cancer Care-Waukesha
  - Wausau, Wisconsin, United States, 54401
    - Aspirus Regional Cancer Center
  - Wausau, Wisconsin, United States, 54401
    - Marshfield Clinic-Wausau Center
  - Wauwatosa, Wisconsin, United States, 53226
    - Aurora Cancer Care-Milwaukee West
  - West Allis, Wisconsin, United States, 53227
    - Aurora West Allis Medical Center
  - Weston, Wisconsin, United States, 54476
    - Marshfield Medical Center - Weston
  - Wisconsin Rapids, Wisconsin, United States, 54494
    - Aspirus Cancer Care - Wisconsin Rapids
  - Wisconsin Rapids, Wisconsin, United States, 54494
    - Marshfield Clinic - Wisconsin Rapids Center
- Wyoming
  - Casper, Wyoming, United States, 82609
    - Rocky Mountain Oncology
  - Cheyenne, Wyoming, United States, 82001
    - Cheyenne Regional Medical Center-West
  - Cody, Wyoming, United States, 82414
    - Big Horn Basin Cancer Center
  - Cody, Wyoming, United States, 82414
    - Billings Clinic-Cody
  - Sheridan, Wyoming, United States, 82801
    - Welch Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

Description

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
Age ≥ 18 years and ≤ 70
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)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Interventional Model: Parallel Assignment
Masking: None (Open Label)

Number of Arms

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Arm B (rituximab, fludarabine phosphate, cyclophosphamide) 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.	Other: Laboratory Biomarker Analysis Correlative studies Other: Quality-of-Life Assessment Ancillary studies Other Names: Quality of Life Assessment Other: Pharmacogenomic Study Correlative studies Other Names: PHARMACOGENOMIC Drug: Cyclophosphamide Given IV Other Names: Cytoxan CTX (-)-Cyclophosphamide 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate Carloxan Ciclofosfamida Ciclofosfamide Cicloxal Clafen Claphene CP monohydrate CYCLO-cell Cycloblastin Cycloblastine Cyclophospham Cyclophosphamid monohydrate Cyclophosphamide Monohydrate Cyclophosphamidum Cyclophosphan Cyclophosphane Cyclophosphanum Cyclostin Cyclostine Cytophosphan Cytophosphane Fosfaseron Genoxal Genuxal Ledoxina Mitoxan Neosar Revimmune Syklofosfamid WR- 138719 Asta B 518 B-518 WR-138719 B 518 B518 WR 138719 WR138719 Biological: Rituximab Given IV Other Names: Rituxan MabThera ABP 798 BI 695500 C2B8 Monoclonal Antibody Chimeric Anti-CD20 Antibody CT-P10 IDEC-102 IDEC-C2B8 IDEC-C2B8 Monoclonal Antibody Monoclonal Antibody IDEC-C2B8 PF-05280586 Riabni Rituximab ABBS Rituximab ARRX Rituximab Biosimilar ABP 798 Rituximab Biosimilar BI 695500 Rituximab Biosimilar CT-P10 Rituximab Biosimilar GB241 Rituximab Biosimilar IBI301 Rituximab Biosimilar JHL1101 Rituximab Biosimilar PF-05280586 Rituximab Biosimilar RTXM83 Rituximab Biosimilar SAIT101 Rituximab Biosimilar SIBP-02 rituximab biosimilar TQB2303 Rituximab PVVR Rituximab-arrx Rituximab-pvvr RTXM83 Ruxience Truxima Rixathon Ikgdar Mabtas Rituximab-abbs BI-695500 BI695500 Blitzima IDEC 102 IDEC102 PF 05280586 PF05280586 Ritemvia Rituximab-blit Rituximab-rite Rituximab-rixa Rituximab-rixi Riximyo RTXM 83 RTXM-83 ABP-798 ABP798 CT P10 CTP10 GP 2013 GP-2013 GP2013 Rituximab Biosimilar GP2013 Drug: Fludarabine Phosphate Given IV Other Names: 2-F-ara-AMP Beneflur Fludara 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)- SH T 586
Experimental: Arm A (ibrutinib, rituximab) Patients receive ibrutinib PO QD on days 1-28. Beginning cycle 2, patients also receive rituximab IV over 4 hours on days 1 and 2 of cycle 2, and day 1 of cycles 3-7. Treatment repeats every 28 days for 7 cycles in the absence of unacceptable toxicity. In the absence of disease progression, patients may continue ibrutinib PO QD for a maximum of 10 years.	Other: Laboratory Biomarker Analysis Correlative studies Other: Quality-of-Life Assessment Ancillary studies Other Names: Quality of Life Assessment Other: Pharmacogenomic Study Correlative studies Other Names: PHARMACOGENOMIC Biological: Rituximab Given IV Other Names: Rituxan MabThera ABP 798 BI 695500 C2B8 Monoclonal Antibody Chimeric Anti-CD20 Antibody CT-P10 IDEC-102 IDEC-C2B8 IDEC-C2B8 Monoclonal Antibody Monoclonal Antibody IDEC-C2B8 PF-05280586 Riabni Rituximab ABBS Rituximab ARRX Rituximab Biosimilar ABP 798 Rituximab Biosimilar BI 695500 Rituximab Biosimilar CT-P10 Rituximab Biosimilar GB241 Rituximab Biosimilar IBI301 Rituximab Biosimilar JHL1101 Rituximab Biosimilar PF-05280586 Rituximab Biosimilar RTXM83 Rituximab Biosimilar SAIT101 Rituximab Biosimilar SIBP-02 rituximab biosimilar TQB2303 Rituximab PVVR Rituximab-arrx Rituximab-pvvr RTXM83 Ruxience Truxima Rixathon Ikgdar Mabtas Rituximab-abbs BI-695500 BI695500 Blitzima IDEC 102 IDEC102 PF 05280586 PF05280586 Ritemvia Rituximab-blit Rituximab-rite Rituximab-rixa Rituximab-rixi Riximyo RTXM 83 RTXM-83 ABP-798 ABP798 CT P10 CTP10 GP 2013 GP-2013 GP2013 Rituximab Biosimilar GP2013 Drug: Ibrutinib Given PO Other Names: PCI-32765 Imbruvica BTK Inhibitor PCI-32765 CRA-032765 PCI32765 CRA 032765 CRA032765 PCI 32765

Participant Group / Arm

Intervention / Treatment

Active Comparator: Arm B (rituximab, fludarabine phosphate, cyclophosphamide)

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.

Other: Laboratory Biomarker Analysis

Correlative studies

Other: Quality-of-Life Assessment

Ancillary studies

Other Names:

Quality of Life Assessment

Other: Pharmacogenomic Study

Correlative studies

Other Names:

PHARMACOGENOMIC

Drug: Cyclophosphamide

Given IV

Other Names:

Cytoxan
CTX
(-)-Cyclophosphamide
2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate
Carloxan
Ciclofosfamida
Ciclofosfamide
Cicloxal
Clafen
Claphene
CP monohydrate
CYCLO-cell
Cycloblastin
Cycloblastine
Cyclophospham
Cyclophosphamid monohydrate
Cyclophosphamide Monohydrate
Cyclophosphamidum
Cyclophosphan
Cyclophosphane
Cyclophosphanum
Cyclostin
Cyclostine
Cytophosphan
Cytophosphane
Fosfaseron
Genoxal
Genuxal
Ledoxina
Mitoxan
Neosar
Revimmune
Syklofosfamid
WR- 138719
Asta B 518
B-518
WR-138719
B 518
B518
WR 138719
WR138719

Biological: Rituximab

Given IV

Other Names:

Rituxan
MabThera
ABP 798
BI 695500
C2B8 Monoclonal Antibody
Chimeric Anti-CD20 Antibody
CT-P10
IDEC-102
IDEC-C2B8
IDEC-C2B8 Monoclonal Antibody
Monoclonal Antibody IDEC-C2B8
PF-05280586
Riabni
Rituximab ABBS
Rituximab ARRX
Rituximab Biosimilar ABP 798
Rituximab Biosimilar BI 695500
Rituximab Biosimilar CT-P10
Rituximab Biosimilar GB241
Rituximab Biosimilar IBI301
Rituximab Biosimilar JHL1101
Rituximab Biosimilar PF-05280586
Rituximab Biosimilar RTXM83
Rituximab Biosimilar SAIT101
Rituximab Biosimilar SIBP-02
rituximab biosimilar TQB2303
Rituximab PVVR
Rituximab-arrx
Rituximab-pvvr
RTXM83
Ruxience
Truxima
Rixathon
Ikgdar
Mabtas
Rituximab-abbs
BI-695500
BI695500
Blitzima
IDEC 102
IDEC102
PF 05280586
PF05280586
Ritemvia
Rituximab-blit
Rituximab-rite
Rituximab-rixa
Rituximab-rixi
Riximyo
RTXM 83
RTXM-83
ABP-798
ABP798
CT P10
CTP10
GP 2013
GP-2013
GP2013
Rituximab Biosimilar GP2013

Drug: Fludarabine Phosphate

Given IV

Other Names:

2-F-ara-AMP
Beneflur
Fludara
9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)-
SH T 586

Experimental: Arm A (ibrutinib, rituximab)

Patients receive ibrutinib PO QD on days 1-28. Beginning cycle 2, patients also receive rituximab IV over 4 hours on days 1 and 2 of cycle 2, and day 1 of cycles 3-7. Treatment repeats every 28 days for 7 cycles in the absence of unacceptable toxicity. In the absence of disease progression, patients may continue ibrutinib PO QD for a maximum of 10 years.

Other: Laboratory Biomarker Analysis

Correlative studies

Other: Quality-of-Life Assessment

Ancillary studies

Other Names:

Quality of Life Assessment

Other: Pharmacogenomic Study

Correlative studies

Other Names:

PHARMACOGENOMIC

Biological: Rituximab

Given IV

Other Names:

Rituxan
MabThera
ABP 798
BI 695500
C2B8 Monoclonal Antibody
Chimeric Anti-CD20 Antibody
CT-P10
IDEC-102
IDEC-C2B8
IDEC-C2B8 Monoclonal Antibody
Monoclonal Antibody IDEC-C2B8
PF-05280586
Riabni
Rituximab ABBS
Rituximab ARRX
Rituximab Biosimilar ABP 798
Rituximab Biosimilar BI 695500
Rituximab Biosimilar CT-P10
Rituximab Biosimilar GB241
Rituximab Biosimilar IBI301
Rituximab Biosimilar JHL1101
Rituximab Biosimilar PF-05280586
Rituximab Biosimilar RTXM83
Rituximab Biosimilar SAIT101
Rituximab Biosimilar SIBP-02
rituximab biosimilar TQB2303
Rituximab PVVR
Rituximab-arrx
Rituximab-pvvr
RTXM83
Ruxience
Truxima
Rixathon
Ikgdar
Mabtas
Rituximab-abbs
BI-695500
BI695500
Blitzima
IDEC 102
IDEC102
PF 05280586
PF05280586
Ritemvia
Rituximab-blit
Rituximab-rite
Rituximab-rixa
Rituximab-rixi
Riximyo
RTXM 83
RTXM-83
ABP-798
ABP798
CT P10
CTP10
GP 2013
GP-2013
GP2013
Rituximab Biosimilar GP2013

Drug: Ibrutinib

Given PO

Other Names:

PCI-32765
Imbruvica
BTK Inhibitor PCI-32765
CRA-032765
PCI32765
CRA 032765
CRA032765
PCI 32765

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free Survival (PFS) Rate at 3 Years Time Frame: Assessed every 3 months until progression up to 4 years and 8 months	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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS) Rate at 3 Years Time Frame: 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	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
The Functional Assessment of Cancer Therapy - Leukemia (FACT-Leu) Trial Outcome Index (TOI) Score at 6 Months Time Frame: Assessed 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
The Functional Assessment of Cancer Therapy - Leukemia (FACT-Leu) Trial Outcome Index (TOI) Score at 12 Months Time Frame: Assessed 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
The Association Between Baseline Rai Stage and Complete Response (CR) Rate Time Frame: Assessed at baseline, every 3 months for the first 2 years, and every 6 months for years 3-5	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
Progression-free Survival (PFS) by Measurable Residual Disease (MDR) Status at 2 Years Time Frame: Assessed every 3 months until progression up to 5 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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Distribution of Genetic Abnormalities Before and After Treatment Time Frame: Assessed at baseline, and 3, 6, 12, 15, 18, 24, 36 months	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
T-cell Counts at 12 Months Time Frame: Assessed at 12 months	T-cell counts will be measured at 12 months.	Assessed at 12 months
Association Between Single Nucleotide Polymorphisms (SNPs) and PFS Time Frame: Assessed every 3 months until progression; after progression, assessed every 3 months for first 2 years, every 6 months for years 3-5	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
Prognostic Model to Predict PFS Time Frame: Assessed every 3 months until progression; after progression, assessed every 3 months for first 2 years, every 6 months for years 3-5	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
Signaling Networks Downstream of the B-cell Receptor Time Frame: Assessed at baseline and 3, 6, 12, 15, 18, 24, 36 months	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
Collection of Relapse Samples Time Frame: Assessed at relapse	Collection of relapse samples to study mechanisms of resistance to protocol treatments.	Assessed at relapse

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Cancer Institute (NCI)

Investigators

Principal Investigator: Tait D Shanafelt, ECOG-ACRIN Cancer Research Group

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Related Info

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 10, 2014

Primary Completion (Actual)

October 24, 2018

Study Completion (Estimated)

October 9, 2026

Study Registration Dates

First Submitted

January 27, 2014

First Submitted That Met QC Criteria

January 27, 2014

First Posted (Estimated)

January 29, 2014

Study Record Updates

Last Update Posted (Actual)

May 29, 2026

Last Update Submitted That Met QC Criteria

May 28, 2026

Last Verified

April 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

NCI-2014-00118 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
U10CA180820 (U.S. NIH Grant/Contract)
U24CA196172 (U.S. NIH Grant/Contract)
U10CA021115 (U.S. NIH Grant/Contract)
E1912 (Other Identifier: CTEP)
ECOG-E1912
R01CA193541 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

IPD Plan Description

Individual participant data may be made available upon request as per the ECOG-ACRIN Data Sharing Policy.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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

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)

Study Overview

Status

Conditions

Intervention / Treatment

Detailed Description

Study Type

Enrollment (Actual)

Phase

Contacts and Locations

Study Locations

Participation Criteria

Eligibility Criteria

Ages Eligible for Study

Accepts Healthy Volunteers

Description

Study Plan

How is the study designed?

Design Details

Number of Arms

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure

Measure Description

Time Frame

Secondary Outcome Measures

Outcome Measure

Measure Description

Time Frame

Other Outcome Measures

Outcome Measure

Measure Description

Time Frame

Collaborators and Investigators

Sponsor

Investigators

Publications and helpful links

General Publications

Helpful Links

Study record dates

Study Major Dates

Study Start (Actual)

Primary Completion (Actual)

Study Completion (Estimated)

Study Registration Dates

First Submitted

First Submitted That Met QC Criteria

First Posted (Estimated)

Study Record Updates

Last Update Posted (Actual)

Last Update Submitted That Met QC Criteria

Last Verified

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Plan for Individual participant data (IPD)

IPD Plan Description

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Studies a U.S. FDA-regulated device product

Clinical Trials on Anemia

Clinical Trials on Laboratory Biomarker Analysis

Search Similar Trials

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Medical Conditions

Drug Interventions

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Conditions

Rare Diseases

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