A Comparison of Three Chemotherapy Regimens for the Treatment of Patients With Newly Diagnosed Mantle Cell Lymphoma

June 21, 2023 updated by: ECOG-ACRIN Cancer Research Group

A Randomized 3-Arm Phase II Study Comparing 1.) Bendamustine, Rituximab and High Dose Cytarabine (BR/CR) 2.) Bendamustine, Rituximab, High Dose Cytarabine and Acalabrutinib (BR/CR-A), and 3.) Bendamustine, Rituximab and Acalabrutinib (BR-A) in Patients </= 70 Years Old With Untreated Mantle Cell Lymphoma

This phase II trial compares three chemotherapy regimens consisting of bendamustine, rituximab, high dose cytarabine, and acalabrutinib and studies how well they work in treating patients with newly diagnosed mantle cell lymphoma. Drugs used in chemotherapy, such as bendamustine and cytarabine, 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. Monoclonal antibodies, such as rituximab, may interfere with the ability of cancer cells to grow and spread. Acalabrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. This study is being done to find out if one the drug combinations of bendamustine, rituximab, high dose cytarabine, and acalabrutinib is better or worse than the usual approach for mantle cell lymphoma.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

PRIMARY OBJECTIVE:

I. Positron mission tomography (PET)/computed tomography (CT) complete response (CR)/peripheral blood minimal residual disease (MRD) negative rate.

SECONDARY OBJECTIVES:

I. Progression-free survival at 36 months. II. Toxicity rates (incidence of grade 3/4 infections, renal and neurologic toxicities, cumulative dose of cytarabine & acalabrutinib, dose reduction, and treatment discontinuation due to toxicity).

III. Objective response rate (ORR). IV. Overall survival at 36 months. V. Mobilization failure rate (defined as a yield < 2 x 10^6 CD34+ stem cells/kg with a maximum of 4 courses of apheresis).

VI. To compare PET/CT negative rate between the three arms. VII. To evaluate the association between baseline PET quantitative assessment (qPET) and MRD status at end of treatment (EOT).

VIII. To evaluate the association between the change of qPET parameters from baseline to EOT and MRD, and compare this association across all 3 arms.

IX. To determine the incremental prognostic value of baseline qPET to standard risk markers (Mantle Cell Lymphoma International Prognostic Index [MIPI]) in predicting MRD status at EOT.

X. To determine the prognostic value of baseline, interim and EOT PET in predicting progression-free survival (PFS).

EXPLORATORY IMAGING OBJECTIVES:

I. Interim PET status both qualitatively (Deauville) and quantitatively will be correlated with MRD status at EOT (end of induction).

II. Explore the incremental prognostic value of interim qPET to standard risk markers (MIPI) in predicting MRD status at EOT.

III. Explore the incremental prognostic value of interim qPET to Ki67 in predicting MRD status at EOT.

IV. Explore the association of interim and EOT PET with overall survival (OS).

OUTLINE: Patients are randomized to 1 of 3 arms.

ARM A: Patients receive bendamustine intravenously (IV) on days 1 and 2 and rituximab IV on day 1 or 2. Treatment repeats every 28 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity. Beginning cycle 4, patients receive rituximab IV on day 1 and cytarabine IV every 12 hours (Q12 hours) on days 1 and 2. Treatment repeats every 28 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity.

ARM B: Patients receive acalabrutinib orally (PO) twice daily (BID) on days 1-28, bendamustine IV on days 1 and 2, and rituximab IV on day 1 or 2. Treatment repeats every 28 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity. Beginning cycle 4, patients receive acalabrutinib PO BID on days 1-7 and 22-28, rituximab IV on day 1, and cytarabine IV Q12 hours on days 1 and 2. Treatment repeats every 28 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity.

ARM C: Patients receive acalabrutinib PO BID on days 1-28, bendamustine IV on days 1 and 2, and rituximab IV on day 1 or 2. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 3 years, and then every 6 months until year 10.

Study Type

Interventional

Enrollment (Actual)

360

Phase

  • Phase 2

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
    • 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
      • Fairbanks, Alaska, United States, 99701
        • Fairbanks Memorial Hospital
    • Arizona
      • Phoenix, Arizona, United States, 85004
        • Cancer Center at Saint Joseph's
      • Tucson, Arizona, United States, 85719
        • Banner University Medical Center - Tucson
      • Tucson, Arizona, United States, 85719
        • University of Arizona Cancer Center-North Campus
    • Arkansas
      • Fort Smith, Arkansas, United States, 72903
        • Mercy Hospital Fort Smith
      • Hot Springs, Arkansas, United States, 71913
        • CHI Saint Vincent Cancer Center Hot Springs
    • California
      • Anaheim, California, United States, 92806
        • Kaiser Permanente-Anaheim
      • Arroyo Grande, California, United States, 93420
        • Mission Hope Medical Oncology - Arroyo Grande
      • Baldwin Park, California, United States, 91706
        • Kaiser Permanente-Baldwin Park
      • Bellflower, California, United States, 90706
        • Kaiser Permanente-Bellflower
      • Burbank, California, United States, 91505
        • Providence Saint Joseph Medical Center/Disney Family Cancer Center
      • Fontana, California, United States, 92335
        • Kaiser Permanente-Fontana
      • Harbor City, California, United States, 90710
        • Kaiser Permanente - Harbor City
      • 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
      • Ontario, California, United States, 91761
        • Kaiser Permanente-Ontario
      • Orange, California, United States, 92868
        • UC Irvine Health/Chao Family Comprehensive Cancer Center
      • Palm Springs, California, United States, 92262
        • Desert Regional Medical Center
      • Panorama City, California, United States, 91402
        • Kaiser Permanente - Panorama City
      • Riverside, California, United States, 92505
        • Kaiser Permanente-Riverside
      • Sacramento, California, United States, 95816
        • Mercy Cancer Center - Sacramento
      • San Diego, California, United States, 92120
        • Kaiser Permanente-San Diego Zion
      • San Diego, California, United States, 92108
        • Kaiser Permanente-San Diego Mission
      • 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
      • Santa Maria, California, United States, 93444
        • Mission Hope Medical Oncology - Santa Maria
      • Woodland, California, United States, 95695
        • Woodland Memorial Hospital
      • 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, 80301
        • Boulder Community Hospital
      • Boulder, Colorado, United States, 80303
        • Boulder Community Foothills Hospital
      • Boulder, Colorado, United States, 80304
        • Rocky Mountain Cancer Centers-Boulder
      • Centennial, Colorado, United States, 80112
        • Rocky Mountain Cancer Centers - Centennial
      • Colorado Springs, Colorado, United States, 80907
        • Penrose-Saint Francis Healthcare
      • Colorado Springs, Colorado, United States, 80907
        • Rocky Mountain Cancer Centers-Penrose
      • Colorado Springs, Colorado, United States, 80923
        • Saint Francis Cancer Center
      • Denver, Colorado, United States, 80210
        • Porter Adventist Hospital
      • Denver, Colorado, United States, 80218
        • Presbyterian - Saint Lukes Medical Center - Health One
      • Denver, Colorado, United States, 80218
        • SCL Health Saint Joseph Hospital
      • 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, 80218
        • Colorado Blood Cancer Institute
      • Denver, Colorado, United States, 80204
        • Cancer Center of Colorado at Sloan's Lake
      • Denver, Colorado, United States, 80209
        • The Women's Imaging Center
      • Denver, Colorado, United States, 80206
        • National Jewish Health-Main Campus
      • Denver, Colorado, United States, 80220
        • Western Surgical Care
      • Durango, Colorado, United States, 81301
        • Mercy Medical Center
      • Durango, Colorado, United States, 81301
        • Southwest Oncology PC
      • Englewood, Colorado, United States, 80113
        • Mountain Blue Cancer Care Center - Swedish
      • Englewood, Colorado, United States, 80113
        • Swedish Medical Center
      • Englewood, Colorado, United States, 80113
        • Rocky Mountain Cancer Centers - Swedish
      • Englewood, Colorado, United States, 80113
        • The Melanoma and Skin Cancer Institute
      • Golden, Colorado, United States, 80401
        • National Jewish Health-Western Hematology Oncology
      • Grand Junction, Colorado, United States, 81501
        • Saint Mary's Hospital and Regional Medical Center
      • Greeley, Colorado, United States, 80631
        • North Colorado Medical Center
      • Lafayette, Colorado, United States, 80026
        • Good Samaritan Medical Center
      • Lakewood, Colorado, United States, 80228
        • Saint Anthony Hospital
      • Lakewood, Colorado, United States, 80228
        • Rocky Mountain Cancer Centers-Lakewood
      • Littleton, Colorado, United States, 80120
        • Rocky Mountain Cancer Centers-Littleton
      • Littleton, Colorado, United States, 80122
        • Littleton Adventist Hospital
      • 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
        • McKee Medical Center
      • Parker, Colorado, United States, 80138
        • Parker Adventist Hospital
      • Pueblo, Colorado, United States, 81004
        • Saint Mary Corwin Medical Center
      • Thornton, Colorado, United States, 80260
        • Rocky Mountain Cancer Centers-Thornton
      • Thornton, Colorado, United States, 80260
        • National Jewish Health-Northern Hematology Oncology
      • Wheat Ridge, Colorado, United States, 80033
        • SCL Health Lutheran Medical Center
    • District of Columbia
      • Washington, District of Columbia, United States, 20016
        • Sibley Memorial Hospital
    • Florida
      • Jacksonville, Florida, United States, 32224-9980
        • Mayo Clinic in Florida
    • Georgia
      • Atlanta, Georgia, United States, 30308
        • Emory University Hospital Midtown
      • Atlanta, Georgia, United States, 30322
        • Emory University Hospital/Winship Cancer Institute
      • Atlanta, Georgia, United States, 30342
        • Emory Saint Joseph's Hospital
    • Idaho
      • Boise, Idaho, United States, 83706
        • Saint Alphonsus Cancer Care Center-Boise
      • Boise, Idaho, United States, 83712
        • Saint Luke's Cancer Institute - Boise
      • Caldwell, Idaho, United States, 83605
        • Saint Alphonsus Cancer Care Center-Caldwell
      • Coeur d'Alene, Idaho, United States, 83814
        • Kootenai Health - Coeur d'Alene
      • Emmett, Idaho, United States, 83617
        • Walter Knox Memorial Hospital
      • Fruitland, Idaho, United States, 83619
        • Saint Luke's Cancer Institute - Fruitland
      • Meridian, Idaho, United States, 83642
        • Idaho Urologic Institute-Meridian
      • Meridian, Idaho, United States, 83642
        • Saint Luke's Cancer Institute - Meridian
      • Nampa, Idaho, United States, 83686
        • Saint Alphonsus Medical Center-Nampa
      • Nampa, Idaho, United States, 83686
        • Saint Luke's Cancer Institute - Nampa
      • Post Falls, Idaho, United States, 83854
        • Kootenai Clinic Cancer Services - Post Falls
      • Sandpoint, Idaho, United States, 83864
        • Kootenai Cancer Clinic
      • Twin Falls, Idaho, United States, 83301
        • Saint Luke's Cancer Institute - Twin Falls
    • Illinois
      • Alton, Illinois, United States, 62002
        • Saint Anthony's Health
      • Aurora, Illinois, United States, 60504
        • Rush - Copley Medical Center
      • Barrington, Illinois, United States, 60010
        • Advocate Good Shepherd Hospital
      • Bloomington, Illinois, United States, 61704
        • Illinois CancerCare-Bloomington
      • Burr Ridge, Illinois, United States, 60527
        • Loyola Center for Health at Burr Ridge
      • Canton, Illinois, United States, 61520
        • Illinois CancerCare-Canton
      • Carbondale, Illinois, United States, 62902
        • Memorial Hospital of Carbondale
      • Carterville, Illinois, United States, 62918
        • SIH Cancer Institute
      • 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
      • Chicago, Illinois, United States, 60612
        • John H Stroger Jr Hospital of Cook County
      • Chicago, Illinois, United States, 60657
        • Advocate Illinois Masonic Medical Center
      • Crystal Lake, Illinois, United States, 60014
        • AMG Crystal Lake - Oncology
      • Danville, Illinois, United States, 61832
        • Carle on Vermilion
      • DeKalb, Illinois, United States, 60115
        • Northwestern Medicine Cancer Center Kishwaukee
      • Decatur, Illinois, United States, 62526
        • Decatur Memorial Hospital
      • Decatur, Illinois, United States, 62526
        • Cancer Care Specialists of Illinois - Decatur
      • Dixon, Illinois, United States, 61021
        • Illinois CancerCare-Dixon
      • Downers Grove, Illinois, United States, 60515
        • Advocate Good Samaritan Hospital
      • Effingham, Illinois, United States, 62401
        • Crossroads Cancer Center
      • Effingham, Illinois, United States, 62401
        • Carle Physician Group-Effingham
      • Elgin, Illinois, United States, 60123
        • Advocate Sherman Hospital
      • 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
      • Harvey, Illinois, United States, 60426
        • Ingalls Memorial Hospital
      • Hazel Crest, Illinois, United States, 60429
        • Advocate South Suburban Hospital
      • Highland Park, Illinois, United States, 60035
        • NorthShore University HealthSystem-Highland Park Hospital
      • Homer Glen, Illinois, United States, 60491
        • Loyola Medicine Homer Glen
      • Kewanee, Illinois, United States, 61443
        • Illinois CancerCare-Kewanee Clinic
      • Lake Forest, Illinois, United States, 60045
        • Northwestern Medicine Lake Forest Hospital
      • Libertyville, Illinois, United States, 60048
        • Condell Memorial Hospital
      • 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
      • Melrose Park, Illinois, United States, 60160
        • Marjorie Weinberg Cancer Center at Loyola-Gottlieb
      • Mount Vernon, Illinois, United States, 62864
        • Good Samaritan Regional Health Center
      • New Lenox, Illinois, United States, 60451
        • UC Comprehensive Cancer Center at Silver Cross
      • O'Fallon, Illinois, United States, 62269
        • Cancer Care Center of O'Fallon
      • Oak Lawn, Illinois, United States, 60453-2699
        • Advocate Christ Medical Center
      • Orland Park, Illinois, United States, 60462
        • University of Chicago Medicine-Orland Park
      • Ottawa, Illinois, United States, 61350
        • Illinois CancerCare-Ottawa Clinic
      • Park Ridge, Illinois, United States, 60068
        • Advocate Lutheran General Hospital
      • Pekin, Illinois, United States, 61554
        • Illinois CancerCare-Pekin
      • Pekin, Illinois, United States, 61554
        • OSF Saint Francis Radiation Oncology at Pekin Cancer Treatment Center
      • 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
      • Springfield, Illinois, United States, 62781
        • Memorial Medical Center
      • Springfield, Illinois, United States, 62702
        • Southern Illinois University School of Medicine
      • Springfield, Illinois, United States, 62702
        • Springfield Clinic
      • Swansea, Illinois, United States, 62226
        • Southwest Illinois Health Services LLP
      • 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
      • Washington, Illinois, United States, 61571
        • Illinois CancerCare - Washington
      • Yorkville, Illinois, United States, 60560
        • Rush-Copley Healthcare Center
    • Iowa
      • Ames, Iowa, United States, 50010
        • McFarland Clinic PC - Ames
      • Ames, Iowa, United States, 50010
        • Mary Greeley Medical Center
      • Boone, Iowa, United States, 50036
        • McFarland Clinic PC-Boone
      • Carroll, Iowa, United States, 51401
        • Saint Anthony Regional Hospital
      • Clive, Iowa, United States, 50325
        • Mercy Cancer Center-West Lakes
      • Clive, Iowa, United States, 50325
        • Medical Oncology and Hematology Associates-West Des Moines
      • Council Bluffs, Iowa, United States, 51503
        • Alegent Health Mercy Hospital
      • Creston, Iowa, United States, 50801
        • Greater Regional Medical Center
      • Des Moines, Iowa, United States, 50309
        • Iowa Methodist Medical Center
      • Des Moines, Iowa, United States, 50314
        • Mercy Medical Center - Des Moines
      • Des Moines, Iowa, United States, 50309
        • Medical Oncology and Hematology Associates-Des Moines
      • Des Moines, Iowa, United States, 50314
        • Broadlawns Medical Center
      • Des Moines, Iowa, United States, 50314
        • Mission Cancer and Blood - Laurel
      • Des Moines, Iowa, United States, 50316
        • Iowa Lutheran Hospital
      • Fort Dodge, Iowa, United States, 50501
        • McFarland Clinic PC-Trinity Cancer Center
      • Fort Dodge, Iowa, United States, 50501
        • Trinity Regional Medical Center
      • Jefferson, Iowa, United States, 50129
        • McFarland Clinic PC-Jefferson
      • Marshalltown, Iowa, United States, 50158
        • McFarland Clinic PC-Marshalltown
      • West Des Moines, Iowa, United States, 50266-7700
        • Methodist West Hospital
      • West Des Moines, Iowa, United States, 50266
        • Mercy Medical Center-West Lakes
    • Kansas
      • Garden City, Kansas, United States, 67846
        • Central Care Cancer Center - Garden City
      • Great Bend, Kansas, United States, 67530
        • Central Care Cancer Center - Great Bend
      • Hays, Kansas, United States, 67601
        • HaysMed University of Kansas Health System
      • Kansas City, Kansas, United States, 66160
        • University of Kansas Cancer Center
      • Lawrence, Kansas, United States, 66044
        • Lawrence Memorial Hospital
      • Olathe, Kansas, United States, 66061
        • Olathe Health Cancer Center
      • Overland Park, Kansas, United States, 66210
        • University of Kansas Cancer Center-Overland Park
      • Pittsburg, Kansas, United States, 66762
        • Ascension Via Christi - Pittsburg
      • Salina, Kansas, United States, 67401
        • Salina Regional Health Center
      • Topeka, Kansas, United States, 66606
        • University of Kansas Health System Saint Francis Campus
      • Topeka, Kansas, United States, 66606
        • Cotton O'Neil Cancer Center / Stormont Vail Health
      • Westwood, Kansas, United States, 66205
        • University of Kansas Hospital-Westwood Cancer Center
    • Kentucky
      • Bardstown, Kentucky, United States, 40004
        • Flaget Memorial Hospital
      • Corbin, Kentucky, United States, 40701
        • Commonwealth Cancer Center-Corbin
      • Lexington, Kentucky, United States, 40504
        • Saint Joseph Radiation Oncology Resource Center
      • Lexington, Kentucky, United States, 40509
        • Saint Joseph Hospital East
      • Lexington, Kentucky, United States, 40504
        • Saint Joseph Hospital
      • London, Kentucky, United States, 40741
        • Saint Joseph London
      • 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
      • Mount Sterling, Kentucky, United States, 40353
        • Saint Joseph Mount Sterling
      • Shepherdsville, Kentucky, United States, 40165
        • Jewish Hospital Medical Center South
    • Louisiana
      • 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
    • Maine
      • Bangor, Maine, United States, 04401
        • Eastern Maine Medical Center
      • Brewer, Maine, United States, 04412
        • Lafayette Family Cancer Center-EMMC
    • Maryland
      • Baltimore, Maryland, United States, 21287
        • Johns Hopkins University/Sidney Kimmel Cancer Center
    • Massachusetts
      • Worcester, Massachusetts, United States, 01655
        • UMass Memorial Medical Center - University Campus
    • Michigan
      • Adrian, Michigan, United States, 49221
        • Hickman Cancer Center
      • Ann Arbor, Michigan, United States, 48109
        • University of Michigan Comprehensive Cancer Center
      • Battle Creek, Michigan, United States, 49017
        • Bronson Battle Creek
      • Detroit, Michigan, United States, 48201
        • Wayne State University/Karmanos Cancer Institute
      • Farmington Hills, Michigan, United States, 48334
        • Weisberg Cancer Treatment Center
      • Grand Rapids, Michigan, United States, 49503
        • Spectrum Health at Butterworth Campus
      • Grand Rapids, Michigan, United States, 49503
        • Helen DeVos Children's Hospital at Spectrum Health
      • Grand Rapids, Michigan, United States, 49503
        • Mercy Health Saint Mary's
      • Kalamazoo, Michigan, United States, 49007
        • West Michigan Cancer Center
      • Kalamazoo, Michigan, United States, 49007
        • Bronson Methodist Hospital
      • Kalamazoo, Michigan, United States, 49048
        • Borgess Medical Center
      • Kalamazoo, Michigan, United States, 49009
        • Ascension Borgess Cancer Center
      • Monroe, Michigan, United States, 48162
        • Toledo Clinic Cancer Centers-Monroe
      • Muskegon, Michigan, United States, 49444
        • Mercy Health Mercy Campus
      • Niles, Michigan, United States, 49120
        • Lakeland Hospital Niles
      • Norton Shores, Michigan, United States, 49444
        • Cancer and Hematology Centers of Western Michigan - Norton Shores
      • Reed City, Michigan, United States, 49677
        • Spectrum Health Reed City Hospital
      • Saint Joseph, Michigan, United States, 49085
        • Lakeland Medical Center Saint Joseph
      • Saint Joseph, Michigan, United States, 49085
        • Marie Yeager Cancer Center
      • Traverse City, Michigan, United States, 49684
        • Munson Medical Center
      • Wyoming, Michigan, United States, 49519
        • Metro Health Hospital
    • Minnesota
      • Aitkin, Minnesota, United States, 56431
        • Riverwood Healthcare Center
      • Baxter, Minnesota, United States, 56425
        • Essentia Health - Baxter Clinic
      • 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
      • Burnsville, Minnesota, United States, 55337
        • Minnesota Oncology - Burnsville
      • Cambridge, Minnesota, United States, 55008
        • Cambridge Medical Center
      • Coon Rapids, Minnesota, United States, 55433
        • Mercy Hospital
      • Deer River, Minnesota, United States, 56636
        • Essentia Health - Deer River Clinic
      • Detroit Lakes, Minnesota, United States, 56501
        • Essentia Health Saint Mary's - Detroit Lakes Clinic
      • 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
      • Ely, Minnesota, United States, 55731
        • Essentia Health - Ely Clinic
      • Fergus Falls, Minnesota, United States, 56537
        • Lake Region Healthcare Corporation-Cancer Care
      • Fosston, Minnesota, United States, 56542
        • Essentia Health - Fosston
      • Fridley, Minnesota, United States, 55432
        • Unity Hospital
      • Hibbing, Minnesota, United States, 55746
        • Essentia Health Hibbing Clinic
      • International Falls, Minnesota, United States, 56649
        • Essentia Health - International Falls Clinic
      • Maple Grove, Minnesota, United States, 55369
        • Fairview Clinics and Surgery Center Maple Grove
      • 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
      • Monticello, Minnesota, United States, 55362
        • Monticello Cancer Center
      • Moose Lake, Minnesota, United States, 55767
        • Essentia Health - Moose Lake Clinic
      • New Ulm, Minnesota, United States, 56073
        • New Ulm Medical Center
      • Park Rapids, Minnesota, United States, 56470
        • Essentia Health - Park Rapids
      • Princeton, Minnesota, United States, 55371
        • Fairview Northland 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 Paul, Minnesota, United States, 55101
        • Regions Hospital
      • Saint Paul, Minnesota, United States, 55102
        • United Hospital
      • Sandstone, Minnesota, United States, 55072
        • Essentia Health Sandstone
      • Shakopee, Minnesota, United States, 55379
        • Saint Francis Regional Medical Center
      • Stillwater, Minnesota, United States, 55082
        • Lakeview Hospital
      • Thief River Falls, Minnesota, United States, 56701
        • Sanford Thief River Falls Medical Center
      • Virginia, Minnesota, United States, 55792
        • Essentia Health Virginia Clinic
      • 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
      • Worthington, Minnesota, United States, 56187
        • Sanford Cancer Center Worthington
      • Wyoming, Minnesota, United States, 55092
        • Fairview Lakes Medical Center
    • Missouri
      • Ballwin, Missouri, United States, 63011
        • Saint Louis Cancer and Breast Institute-Ballwin
      • 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
        • Southeast Cancer Center
      • Chesterfield, Missouri, United States, 63017
        • Saint Luke's Hospital
      • Creve Coeur, Missouri, United States, 63141
        • Siteman Cancer Center at West County Hospital
      • Farmington, Missouri, United States, 63640
        • Parkland Health Center - Farmington
      • Jefferson City, Missouri, United States, 65109
        • Capital Region Southwest Campus
      • Joplin, Missouri, United States, 64804
        • Freeman Health System
      • Joplin, Missouri, United States, 64804
        • Mercy Hospital Joplin
      • Kansas City, Missouri, United States, 64154
        • University of Kansas Cancer Center - North
      • Kansas City, Missouri, United States, 64108
        • Truman Medical Centers
      • Lee's Summit, Missouri, United States, 64064
        • University of Kansas Cancer Center - Lee's Summit
      • Rolla, Missouri, United States, 65401
        • Delbert Day Cancer Institute at PCRMC
      • Rolla, Missouri, United States, 65401
        • Mercy Clinic-Rolla-Cancer and Hematology
      • Saint Joseph, Missouri, United States, 64506
        • Heartland Regional Medical Center
      • Saint Louis, Missouri, United States, 63110
        • Washington University School of Medicine
      • Saint Louis, Missouri, United States, 63131
        • Missouri Baptist Medical Center
      • Saint Louis, Missouri, United States, 63141
        • Mercy Hospital Saint Louis
      • Saint Louis, Missouri, United States, 63128
        • Mercy Hospital South
      • Saint Louis, Missouri, United States, 63129
        • Siteman Cancer Center-South County
      • Saint Louis, Missouri, United States, 63136
        • Siteman Cancer Center at Christian Hospital
      • Saint Louis, Missouri, United States, 63109
        • Saint Louis Cancer and Breast Institute-South City
      • Saint Peters, Missouri, United States, 63376
        • Siteman Cancer Center at Saint Peters Hospital
      • 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
      • Sullivan, Missouri, United States, 63080
        • Missouri Baptist Sullivan Hospital
      • Sunset Hills, Missouri, United States, 63127
        • Missouri Baptist Outpatient Center-Sunset Hills
      • Washington, Missouri, United States, 63090
        • Mercy Hospital Washington
    • 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
        • Saint Vincent Frontier Cancer Center
      • Bozeman, Montana, United States, 59715
        • Bozeman 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 Healthcare- Sletten Cancer Institute
      • Kalispell, Montana, United States, 59901
        • Kalispell Regional Medical Center
      • Missoula, Montana, United States, 59804
        • Community Medical Hospital
      • Missoula, Montana, United States, 59802
        • Saint Patrick Hospital - Community Hospital
    • Nebraska
      • Grand Island, Nebraska, United States, 68803
        • CHI Health Saint Francis
      • Kearney, Nebraska, United States, 68847
        • CHI Health Good Samaritan
      • Lincoln, Nebraska, United States, 68510
        • Saint Elizabeth Regional Medical 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, 68118
        • Nebraska Medicine-Village Pointe
      • 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
      • Papillion, Nebraska, United States, 68046
        • Midlands Community Hospital
    • New Hampshire
      • Lebanon, New Hampshire, United States, 03756
        • Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center
    • New Jersey
      • Morristown, New Jersey, United States, 07960
        • Morristown Medical Center
      • Summit, New Jersey, United States, 07902
        • Overlook Hospital
    • New York
      • Buffalo, New York, United States, 14263
        • Roswell Park Cancer Institute
      • Glens Falls, New York, United States, 12801
        • Glens Falls Hospital
      • New York, New York, United States, 10065
        • NYP/Weill Cornell Medical Center
      • New York, New York, United States, 10016
        • Laura and Isaac Perlmutter Cancer Center at NYU Langone
      • Rochester, New York, United States, 14642
        • University of Rochester
    • North Carolina
      • Chapel Hill, North Carolina, United States, 27599
        • UNC Lineberger Comprehensive Cancer Center
      • Clinton, North Carolina, United States, 28328
        • Southeastern Medical Oncology Center-Clinton
      • Goldsboro, North Carolina, United States, 27534
        • Southeastern Medical Oncology Center-Goldsboro
      • Jacksonville, North Carolina, United States, 28546
        • Southeastern Medical Oncology Center-Jacksonville
      • Kenansville, North Carolina, United States, 28349
        • Vidant Oncology-Kenansville
      • Kinston, North Carolina, United States, 28501
        • Vidant Oncology-Kinston
      • Richlands, North Carolina, United States, 28574
        • Vidant Oncology-Richlands
    • 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
      • Fargo, North Dakota, United States, 58103
        • Sanford South University Medical Center
      • Fargo, North Dakota, United States, 58103
        • Southpointe-Sanford Medical Center Fargo
      • Fargo, North Dakota, United States, 58104
        • Sanford Medical Center Fargo
      • Jamestown, North Dakota, United States, 58401
        • Essentia Health - Jamestown Clinic
    • Ohio
      • 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, 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
      • Cleveland, Ohio, United States, 44195
        • Cleveland Clinic Foundation
      • Columbus, Ohio, United States, 43210
        • Ohio State University Comprehensive Cancer Center
      • Perrysburg, Ohio, United States, 43551
        • Mercy Health Perrysburg Cancer Center
      • Sylvania, Ohio, United States, 43560
        • ProMedica Flower Hospital
      • Toledo, Ohio, United States, 43606
        • ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital
      • Toledo, Ohio, United States, 43623
        • Mercy Health - Saint Anne Hospital
      • Toledo, Ohio, United States, 43623
        • Toledo Clinic Cancer Centers-Toledo
      • West Chester, Ohio, United States, 45069
        • University of Cincinnati Cancer Center-West Chester
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73104
        • University of Oklahoma Health Sciences Center
      • Oklahoma City, Oklahoma, United States, 73120
        • Mercy Hospital Oklahoma City
    • Oregon
      • Baker City, Oregon, United States, 97814
        • Saint Alphonsus Medical Center-Baker City
      • 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
      • Newberg, Oregon, United States, 97132
        • Providence Newberg Medical Center
      • Ontario, Oregon, United States, 97914
        • Saint Alphonsus Medical Center-Ontario
      • Portland, Oregon, United States, 97239
        • Oregon Health and Science University
      • Portland, Oregon, United States, 97213
        • Providence Portland Medical Center
      • Portland, Oregon, United States, 97225
        • Providence Saint Vincent Medical Center
      • Redmond, Oregon, United States, 97756
        • Saint Charles Health System-Redmond
    • Rhode Island
      • Providence, Rhode Island, United States, 02903
        • Rhode Island Hospital
    • South Carolina
      • Boiling Springs, South Carolina, United States, 29316
        • Prisma Health Cancer Institute - Spartanburg
      • Charleston, South Carolina, United States, 29425
        • Medical University of South Carolina
      • Easley, South Carolina, United States, 29640
        • Prisma Health Cancer Institute - Easley
      • Greenville, South Carolina, United States, 29605
        • Prisma Health Cancer Institute - Faris
      • Greenville, South Carolina, United States, 29615
        • Prisma Health Cancer Institute - Eastside
      • Greenville, South Carolina, United States, 29605
        • Prisma Health Cancer Institute - Butternut
      • Greer, South Carolina, United States, 29650
        • Prisma Health Cancer Institute - Greer
      • Seneca, South Carolina, United States, 29672
        • Prisma Health Cancer Institute - Seneca
    • South Dakota
      • 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
    • Texas
      • Bryan, Texas, United States, 77802
        • Saint Joseph Regional Cancer Center
    • Utah
      • American Fork, Utah, United States, 84003
        • American Fork Hospital / Huntsman Intermountain Cancer Center
      • Cedar City, Utah, United States, 84720
        • Sandra L Maxwell Cancer Center
      • Logan, Utah, United States, 84321
        • Logan Regional Hospital
      • Murray, Utah, United States, 84107
        • Intermountain Medical Center
      • Ogden, Utah, United States, 84403
        • McKay-Dee Hospital Center
      • Provo, Utah, United States, 84604
        • Utah Valley Regional Medical Center
      • Riverton, Utah, United States, 84065
        • Riverton Hospital
      • Saint George, Utah, United States, 84770
        • Saint George Regional Medical Center
      • Salt Lake City, Utah, United States, 84112
        • Huntsman Cancer Institute/University of Utah
      • Salt Lake City, Utah, United States, 84106
        • Utah Cancer Specialists-Salt Lake City
      • Salt Lake City, Utah, United States, 84143
        • LDS Hospital
    • Vermont
      • Berlin, 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
      • Saint Johnsbury, Vermont, United States, 05819
        • Norris Cotton Cancer Center-North
    • Virginia
      • Charlottesville, Virginia, United States, 22908
        • University of Virginia Cancer Center
      • Richmond, Virginia, United States, 23298
        • Virginia Commonwealth University/Massey Cancer Center
    • Washington
      • Aberdeen, Washington, United States, 98520
        • Providence Regional Cancer System-Aberdeen
      • Auburn, Washington, United States, 98001
        • MultiCare Auburn Medical Center
      • Bellingham, Washington, United States, 98225
        • PeaceHealth Saint Joseph Medical Center
      • Bremerton, Washington, United States, 98310
        • Harrison HealthPartners Hematology and Oncology-Bremerton
      • Bremerton, Washington, United States, 98310
        • Harrison 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, 98003
        • Saint Francis Hospital
      • 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
        • Kadlec Clinic Hematology and Oncology
      • 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
      • Port Townsend, Washington, United States, 98368
        • Jefferson Healthcare
      • Poulsbo, Washington, United States, 98370
        • Harrison HealthPartners Hematology and Oncology-Poulsbo
      • Puyallup, Washington, United States, 98372
        • MultiCare Good Samaritan Hospital
      • Seattle, Washington, United States, 98107
        • Swedish Medical Center-Ballard Campus
      • Seattle, Washington, United States, 98122
        • Swedish Medical Center-First Hill
      • Seattle, Washington, United States, 98104
        • Pacific Gynecology Specialists
      • Seattle, Washington, United States, 98122-5711
        • Swedish Medical Center-Cherry Hill
      • Sedro-Woolley, Washington, United States, 98284
        • PeaceHealth United General Medical Center
      • Shelton, Washington, United States, 98584
        • Providence Regional Cancer System-Shelton
      • Spokane, Washington, United States, 99204
        • MultiCare Deaconess Cancer and Blood Specialty Center - Downtown
      • Spokane, Washington, United States, 99218
        • MultiCare Deaconess Cancer and Blood Specialty Center - North
      • Spokane Valley, Washington, United States, 99216
        • MultiCare Deaconess Cancer and Blood Specialty Center - Valley
      • Tacoma, Washington, United States, 98405
        • Mary Bridge Children's Hospital and Health Center
      • Tacoma, Washington, United States, 98405
        • Northwest Medical Specialties PLLC
      • Tacoma, Washington, United States, 98405
        • MultiCare Tacoma General Hospital
      • Tacoma, Washington, United States, 98405
        • Franciscan Research Center-Northwest Medical Plaza
      • Vancouver, Washington, United States, 98664
        • PeaceHealth Southwest Medical Center
      • Walla Walla, Washington, United States, 99362
        • Providence Saint Mary Regional Cancer Center
      • Yelm, Washington, United States, 98597
        • Providence Regional Cancer System-Yelm
    • Wisconsin
      • Antigo, Wisconsin, United States, 54409
        • Langlade Hospital and Cancer Center
      • Appleton, Wisconsin, United States, 54911
        • ThedaCare Regional Cancer Center
      • Ashland, Wisconsin, United States, 54806
        • Duluth Clinic Ashland
      • Ashland, Wisconsin, United States, 54806
        • Northwest Wisconsin Cancer Center
      • Burlington, Wisconsin, United States, 53105
        • Aurora Cancer Care-Southern Lakes VLCC
      • Cudahy, Wisconsin, United States, 53110
        • Aurora Saint Luke's South Shore
      • Eau Claire, Wisconsin, United States, 54701
        • Marshfield Medical Center-EC Cancer Center
      • 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
      • Hayward, Wisconsin, United States, 54843
        • Essentia Health-Hayward Clinic
      • Kenosha, Wisconsin, United States, 53142
        • Aurora Cancer Care-Kenosha South
      • La Crosse, Wisconsin, United States, 54601
        • Gundersen Lutheran Medical Center
      • Madison, Wisconsin, United States, 53792
        • University of Wisconsin Carbone Cancer Center
      • Marinette, Wisconsin, United States, 54143
        • Aurora Bay Area Medical Group-Marinette
      • Marshfield, Wisconsin, United States, 54449
        • Marshfield Medical Center-Marshfield
      • Medford, Wisconsin, United States, 54451
        • Aspirus Medford Hospital
      • 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 Clinic-Minocqua Center
      • 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
      • Rice Lake, Wisconsin, United States, 54868
        • Marshfield Medical Center-Rice Lake
      • Sheboygan, Wisconsin, United States, 53081
        • Vince Lombardi Cancer Clinic-Sheboygan
      • Spooner, Wisconsin, United States, 54801
        • Essentia Health-Spooner Clinic
      • Stevens Point, Wisconsin, United States, 54481
        • Ascension Saint Michael's Hospital
      • Stevens Point, Wisconsin, United States, 54482
        • Marshfield Medical Center-River Region at Stevens Point
      • Sturgeon Bay, Wisconsin, United States, 54235-1495
        • Saint Vincent Hospital Cancer Center at Sturgeon Bay
      • Summit, Wisconsin, United States, 53066
        • Aurora Medical Center in Summit
      • Superior, Wisconsin, United States, 54880
        • Essentia Health Saint Mary's Hospital - Superior
      • 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
      • Wausau, Wisconsin, United States, 54401
        • Aspirus Regional Cancer 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
    • Wyoming
      • Cheyenne, Wyoming, United States, 82001
        • Cheyenne Regional Medical Center-West
      • 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

No

Description

Inclusion Criteria:

  • Baseline measurements and evaluations must be obtained within 6 weeks of randomization to the study. Abnormal PET or CT scans may constitute evaluable disease. Patient must have at least one objective measurable disease parameter. Measurable disease in the liver is required if the liver is the only site of lymphoma.
  • MIPI score must be calculated and entered in Oncology Patient Enrollment Network (OPEN).
  • Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status score of 0-2.
  • Patients must have untreated histologically confirmed mantle cell lymphoma, with cyclin D1 (BCL1) expression by immunohistochemical stains and/or t(11;14) by cytogenetics or fluorescent in situ hybridization (FISH). The diagnosis must be confirmed by formal hematopathology review at the enrolling center.
  • Patients being treated with gastric reducing agents proton pump inhibitors must be switched to an alternative drug before starting acalabrutinib.

  • Absolute neutrophil count (ANC) >= 1,000/mcL (obtained with 14 days of randomization). If disease includes marrow involvement or hypersplenism, please reference the below revised ANC requirement:

    • ANC >= 500/mcL

  • Platelets >= 75,000 mcL (obtained with 14 days of randomization). If disease includes involvement or hypersplenism, please reference the below revised platelet requirement:

    • Platelets >= 25,000/mcL

  • Total bilirubin =< 2 x institutional upper limit of normal (ULN) (obtained with 14 days of randomization). If disease includes hepatic infiltration or is causing biliary obstruction, or if elevated bilirubin is due to Gilbert's disease, please reference the below revised bilirubin requirements:

    • Bilirubin =< 3 x institutional ULN

  • Aspartate aminotransferase (AST) and alanine transaminase (ALT) =< 2.5 x institutional ULN (obtained with 14 days of randomization). If disease includes hepatic infiltration or is causing biliary obstruction, or if elevated bilirubin is due to Gilbert's disease, please reference the below revised AST/ALT requirements:

    • AST/ALT =< 5 x institutional ULN
  • Prothrombin time (PT)/international normalized ratio (INR) or partial thromboplastin time (aPTT) in the absence of lupus anticoagulant) < 2 x institutional ULN (obtained with 14 days of randomization). Patients receiving anticoagulant therapy (other than warfarin or equivalent vitamin K antagonists which are excluded), higher INR/aPTT may be permitted to enroll to this study after discussion with the primary investigator (PI).
  • Creatinine =< institutional ULN, OR glomerular filtration rate (GFR) >= 40 mL/min/1.73 m^2 (obtained with 14 days of randomization).
  • Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial.
  • For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.
  • Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load.
  • Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.
  • Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional classification. To be eligible for this trial, patients should be class 2B or better.
  • Patients must have a QT interval (QTc) =< 480 msec obtained within 14 days of randomization.
  • Women must not be pregnant or breast-feeding due to the potential harm to an unborn fetus and possible risk for adverse events in nursing infants with the treatment regimens being used. Patients must also not expect to conceive or father children from the time of registration, while on study treatment, and until 12 months after the last dose of study treatment. All females of childbearing potential must have a blood test or urine study within 2 weeks prior to randomization to rule out pregnancy. A female of childbearing potential is any woman, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: has achieved menarche at some point, has not undergone a hysterectomy or bilateral oophorectomy; or has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months).
  • Women of childbearing potential and sexually active males must agree to use accepted and effective method(s) of contraception or to abstain from sexual intercourse for the duration of their participation in the study and for 12 months after treatment ends.
  • Patients are not eligible if they require treatment with a strong cytochrome P450 (CYP) 3A inhibitor.

  • Patients may not have received the following within 7 days prior to the first dose of study drug:

    • Strong and moderate CYP3A inhibitors
    • Strong and moderate CYP3A inducers

  • Patients are ineligible if they have any of the following:

    • Malabsorption syndrome or disease significantly affecting gastrointestinal function.
    • Active bleeding or history of bleeding diathesis (e.g. hemophilia or von Willebrand disease).
    • Uncontrolled AIHA (autoimmune hemolytic anemia) or ITP (idiopathic thrombocytopenia purpura).
    • Requires or receiving anticoagulation with warfarin or equivalent vitamin K antagonists (e.g. phenprocoumon) within 7 days of first dose of study drug.
    • History of significant cerebrovascular disease/event, including stroke or intracranial hemorrhage, within 6 months before the first dose of study drug.
    • Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infections at study enrollment (defined as exhibiting ongoing signs/symptoms related to the infection and without improvement, despite appropriate antibiotics or other treatment).
    • History of severe allergic reaction attributed to compounds of similar chemical or biologic composition to rituximab, bendamustine, cytarabine, or acalabrutinib.

  • Patients must be able to fulfill one of the following eligibility requirements pertaining to biospecimen availability for submission following randomization:

    • Archived formalin-fixed paraffin-embedded (FFPE) tumor tissue specimen from the original diagnostic biopsy is available for submission OR,

    • If tumor tissue is not available, peripheral blood collected prior to initiation of protocol therapy will be submitted

      • NOTE: Biospecimens must be submitted within 60 days following randomization to Adaptive Biotechnologies for ClonoSEQ ID molecular marker identification of unique clonal immunoglobulin deoxyribonucleic acid (DNA) sequence. If peripheral blood will be submitted, Adaptive Biotechnologies should be contacted prior to patient randomization for guidance pertaining to collection and submission requirements.

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)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Arm A (bendamustine, rituximab, cytarabine)
Patients receive bendamustine IV on days 1 and 2 and rituximab IV on day 1 or 2. Treatment repeats every 28 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity. Beginning cycle 4, patients receive rituximab IV on day 1 and cytarabine IV every Q12 hours on days 1 and 2. Treatment repeats every 28 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity.
Drug: Cytarabine
Given IV
Other Names:
  • .beta.-Cytosine arabinoside
  • 1-.beta.-D-Arabinofuranosyl-4-amino-2(1H)pyrimidinone
  • 1-.beta.-D-Arabinofuranosylcytosine
  • 1-Beta-D-arabinofuranosyl-4-amino-2(1H)pyrimidinone
  • 1-Beta-D-arabinofuranosylcytosine
  • 1.beta.-D-Arabinofuranosylcytosine
  • 2(1H)-Pyrimidinone, 4-Amino-1-beta-D-arabinofuranosyl-
  • 2(1H)-Pyrimidinone, 4-amino-1.beta.-D-arabinofuranosyl-
  • Alexan
  • Ara-C
  • ARA-cell
  • Arabine
  • Arabinofuranosylcytosine
  • Arabinosylcytosine
  • Aracytidine
  • Aracytin
  • Aracytine
  • CHX-3311
  • Cytarabinum
  • Cytarbel
  • Cytosar
  • Cytosine Arabinoside
  • Cytosine-.beta.-arabinoside
  • Cytosine-beta-arabinoside
  • Erpalfa
  • Starasid
  • Tarabine PFS
  • U 19920
  • U-19920
  • Udicil
  • WR-28453
  • Beta-cytosine Arabinoside
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
  • Rituximab ABBS
  • 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 TQB2303
  • rituximab-abbs
  • RTXM83
  • Truxima
Drug: Bendamustine
Given IV
Other Names:
  • SDX-105
Drug: Bendamustine Hydrochloride
Given IV
Other Names:
  • Treanda
  • Bendeka
  • Bendamustin Hydrochloride
  • Cytostasan Hydrochloride
  • Levact
  • Ribomustin
  • SyB L-0501
Experimental: Arm B (acalabrutinib, bendamustine, rituximab, cytarabine)
Patients receive PO BID on days 1-28, bendamustine IV on days 1 and 2, and rituximab IV on day 1 or 2. Treatment repeats every 28 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity. Beginning cycle 4, patients receive acalabrutinib PO BID on days 1-7 and 22-28, rituximab IV on day 1, and cytarabine IV Q12 hours on days 1 and 2. Treatment repeats every 28 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity.
Drug: Cytarabine
Given IV
Other Names:
  • .beta.-Cytosine arabinoside
  • 1-.beta.-D-Arabinofuranosyl-4-amino-2(1H)pyrimidinone
  • 1-.beta.-D-Arabinofuranosylcytosine
  • 1-Beta-D-arabinofuranosyl-4-amino-2(1H)pyrimidinone
  • 1-Beta-D-arabinofuranosylcytosine
  • 1.beta.-D-Arabinofuranosylcytosine
  • 2(1H)-Pyrimidinone, 4-Amino-1-beta-D-arabinofuranosyl-
  • 2(1H)-Pyrimidinone, 4-amino-1.beta.-D-arabinofuranosyl-
  • Alexan
  • Ara-C
  • ARA-cell
  • Arabine
  • Arabinofuranosylcytosine
  • Arabinosylcytosine
  • Aracytidine
  • Aracytin
  • Aracytine
  • CHX-3311
  • Cytarabinum
  • Cytarbel
  • Cytosar
  • Cytosine Arabinoside
  • Cytosine-.beta.-arabinoside
  • Cytosine-beta-arabinoside
  • Erpalfa
  • Starasid
  • Tarabine PFS
  • U 19920
  • U-19920
  • Udicil
  • WR-28453
  • Beta-cytosine Arabinoside
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
  • Rituximab ABBS
  • 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 TQB2303
  • rituximab-abbs
  • RTXM83
  • Truxima
Drug: Bendamustine
Given IV
Other Names:
  • SDX-105
Drug: Acalabrutinib
Given PO
Other Names:
  • Calquence
  • ACP-196
  • Bruton Tyrosine Kinase Inhibitor ACP-196
Drug: Bendamustine Hydrochloride
Given IV
Other Names:
  • Treanda
  • Bendeka
  • Bendamustin Hydrochloride
  • Cytostasan Hydrochloride
  • Levact
  • Ribomustin
  • SyB L-0501
Experimental: Arm C (acalabrutinib, bendamustine, rituximab)
Patients receive acalabrutinib PO BID on days 1-28, bendamustine IV on days 1 and 2, and rituximab IV on day 1 or 2. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity.
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
  • Rituximab ABBS
  • 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 TQB2303
  • rituximab-abbs
  • RTXM83
  • Truxima
Drug: Bendamustine
Given IV
Other Names:
  • SDX-105
Drug: Acalabrutinib
Given PO
Other Names:
  • Calquence
  • ACP-196
  • Bruton Tyrosine Kinase Inhibitor ACP-196
Drug: Bendamustine Hydrochloride
Given IV
Other Names:
  • Treanda
  • Bendeka
  • Bendamustin Hydrochloride
  • Cytostasan Hydrochloride
  • Levact
  • Ribomustin
  • SyB L-0501

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Composite of positron emission tomography (PET)/computed tomography (CT) complete response (CR) and peripheral blood (PB) minimal residual disease (MRD) negative rate
Time Frame: Up to 8 weeks post treatment
MRD status is defined as positive, negative, or indeterminate as measured from PB specimens following completion of treatment. Measures of frequencies and proportion, and location and dispersion will be used to describe categorical, and continuous variables respectively; 90% confidence intervals around these estimates will be computed. Kaplan-Meier method will be used to describe time-to-event endpoints and log-rank test to assess difference in time-to-event endpoints by levels of a categorical predictor. Cox proportional hazards (PH) regression model would be used to model the impact of baseline and other relevant variables on time-to-event endpoints.
Up to 8 weeks post treatment

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression-free survival (PFS)
Time Frame: From randomization to earliest of disease progression or death, assessed at 36 months
From randomization to earliest of disease progression or death, assessed at 36 months
Incidence of adverse events
Time Frame: Up to 10 years post randomization
Assessed by Common Terminology Criteria for Adverse Events (CTCAE). The cumulative dose of high dose cytarabine and proportion of patients that discontinued treatment due to toxicity will be assessed.
Up to 10 years post randomization
Objective response rate (ORR)
Time Frame: Up to 10 years post randomization
ORR is defined as the proportion of patients achieving a best response to treatment of complete response (CR) or partial response (PR). ORR and PET/CT CR will be estimated in each treatment arm in the efficacy population, as well as among all treated patients, regardless of informative tissue status.
Up to 10 years post randomization
Overall survival (OS)
Time Frame: From randomization to death, assessed at 36 months
Patients that are alive will be censored at the time of last follow-up. OS will be described using the Kaplan-Meier method and log-rank test will be used to compare survival by treatment arm.
From randomization to death, assessed at 36 months
Mobilization failure rate
Time Frame: Up to 10 years post randomization
Defined as a yield < 2 x10^6 CD34+ stem cells/kg with a maximum of 4 course of apheresis will be summarized as a categorical variable, and compared, between treatment arms using Z- test.
Up to 10 years post randomization

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
PET/CT negative rate between the three arms
Time Frame: Up to 10 years post randomization
Up to 10 years post randomization
PET quantitative assessment (qPET)
Time Frame: At end of treatment (within 6 months after the "8 weeks post treatment" timeframe)
Will evaluate the association between baseline qPET and MRD status.
At end of treatment (within 6 months after the "8 weeks post treatment" timeframe)
Change of qPET parameters
Time Frame: Baseline to end of treatment (within 6 months after the "8 weeks post treatment" timeframe)
Will evaluate the association between the change of qPET parameters and MRD and compare this association across all 3 arms.
Baseline to end of treatment (within 6 months after the "8 weeks post treatment" timeframe)
Incremental prognostic value of baseline qPET to standard risk markers (Mantle Cell Lymphoma International Prognostic Index [MIPI])
Time Frame: At end of treatment (within 6 months after the "8 weeks post treatment" timeframe)
Will assess the incremental prognostic value of baseline to standard risk markers (MIPI) in predicting MRD status.
At end of treatment (within 6 months after the "8 weeks post treatment" timeframe)
Interim PET status
Time Frame: At end of treatment (within 6 months after the "8 weeks post treatment" timeframe)
Interim PET status both qualitatively (Deauville) and quantitatively will be correlated with MRD status. Will fit a logistic regression model to evaluate this aim with binary MRD status at end of treatment (EOT) as the response variable and interim PET status as the predictor.
At end of treatment (within 6 months after the "8 weeks post treatment" timeframe)
Incremental prognostic value of interim qPET to standard risk markers (MIPI)
Time Frame: At end of treatment (within 6 months after the "8 weeks post treatment" timeframe)
Will assess the incremental prognostic value of interim qPET to standard risk markers (MIPI) in predicting MRD status.
At end of treatment (within 6 months after the "8 weeks post treatment" timeframe)
Incremental prognostic value of interim qPET to Ki67
Time Frame: At end of treatment (within 6 months after the "8 weeks post treatment" timeframe)
Will assess the incremental prognostic value of interim qPET to Ki67 in predicting MRD status.
At end of treatment (within 6 months after the "8 weeks post treatment" timeframe)
Incremental prognostic value of baseline qPET to Ki67
Time Frame: At end of treatment (within 6 months after the "8 weeks post treatment" timeframe)
Will assess the incremental prognostic value of baseline qPET to Ki67 in predicting MRD status.
At end of treatment (within 6 months after the "8 weeks post treatment" timeframe)

Collaborators and Investigators

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

Sponsor

ECOG-ACRIN Cancer Research Group

Collaborators

National Cancer Institute (NCI)

Investigators

  • Principal Investigator: Nina D Wagner-Johnston, ECOG-ACRIN Cancer Research Group

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)

December 13, 2019

Primary Completion (Estimated)

December 31, 2024

Study Completion (Estimated)

March 31, 2025

Study Registration Dates

First Submitted

September 6, 2019

First Submitted That Met QC Criteria

October 2, 2019

First Posted (Actual)

October 4, 2019

Study Record Updates

Last Update Posted (Actual)

June 22, 2023

Last Update Submitted That Met QC Criteria

June 21, 2023

Last Verified

June 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • EA4181 (Other Identifier: CTEP)
  • U10CA180820 (U.S. NIH Grant/Contract)
  • NCI-2019-05536 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

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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