Azacitidine With or Without Nivolumab or Midostaurin, or Decitabine and Cytarabine Alone in Treating Older Patients With Newly Diagnosed Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndrome

November 7, 2023 updated by: National Cancer Institute (NCI)

A Randomized Phase II/III Trial of "Novel Therapeutics" Versus Azacitidine in Newly Diagnosed Patients With Acute Myeloid Leukemia (AML) or High-Risk Myelodysplastic Syndrome (MDS), Age 60 or Older LEAP: Less-Intense AML Platform Trial

This randomized phase II/III trial studies how well azacitidine with or without nivolumab or midostaurin, or decitabine and cytarabine alone work in treating older patients with newly diagnosed acute myeloid leukemia or high-risk myelodysplastic syndrome. Drugs used in chemotherapy, such as azacitidine, decitabine, 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. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Midostaurin may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving azacitidine with or without nivolumab or midostaurin, or decitabine and cytarabine alone may kill more cancer cells.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

PRIMARY OBJECTIVES:

I. To select, based on overall survival, any or all of the "Novel Therapeutic" regimens for further testing against azacitidine in patients age 60 and older with newly diagnosed acute myeloid leukemia (AML) or myelodysplastic syndrome with excessive blasts-2 (MDS-EB-2). (Phase II) II. To compare overall survival of the "Novel Therapeutic" regimens selected in the phase II portion of the trial to azacitidine in these patient populations. (Phase III)

SECONDARY OBJECTIVES:

I. To estimate the frequency and severity of toxicities of the regimens in these patient populations.

II. To estimate response rates, event-free survival, and relapse-free survival for these regimens in these patient populations.

TERTIARY OBJECTIVES:

I. To investigate associations between cytogenetic and molecular abnormalities (including FLT3) and outcomes for each of the regimens in these patient populations.

II. To bank specimens for future correlative studies.

OUTLINE: Patients are randomized to 1 of 4 arms.

ARM A: Patients receive azacitidine subcutaneously (SC) or intravenously (IV) daily on days 1-7 or on an interrupted schedule which ensures that all 7 days of therapy are received within a 12 day period. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

ARM B: Patients receive azacitidine as in Arm A and nivolumab IV over 30-60 minutes on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

ARM C: Patients receive azacitidine as in Arm A and midostaurin orally (PO) twice daily (BID) on days 8-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

ARM D:

INDUCTION: Patients receive decitabine IV over 2 hours on days 1-5 and cytarabine IV continuously on days 6-11. Treatment repeats every 28 days for up to 2 courses in the absence of disease progression or unacceptable toxicity.

MAINTENANCE: Patients deemed stable at the discretion of the treating physician receive decitabine as in Induction. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 1 year, every 6 months for 2 years, then annually for 2 years.

Study Type

Interventional

Enrollment (Actual)

78

Phase

  • Phase 2
  • 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
    • 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
    • Arizona
      • Tucson, Arizona, United States, 85704
        • University of Arizona Cancer Center-Orange Grove Campus
      • Tucson, Arizona, United States, 85719
        • Banner University Medical Center - Tucson
      • Tucson, Arizona, United States, 85719
        • University of Arizona Cancer Center-North Campus
    • Arkansas
      • Hot Springs, Arkansas, United States, 71913
        • CHI Saint Vincent Cancer Center Hot Springs
      • Little Rock, Arkansas, United States, 72205
        • John L McClellan Memorial Veterans Hospital
    • California
      • Antioch, California, United States, 94531
        • Kaiser Permanente-Deer Valley Medical Center
      • Burbank, California, United States, 91505
        • Providence Saint Joseph Medical Center/Disney Family Cancer Center
      • Fremont, California, United States, 94538
        • Kaiser Permanente-Fremont
      • Fresno, California, United States, 93720
        • Kaiser Permanente-Fresno
      • Fresno, California, United States, 93720
        • Fresno Cancer Center
      • Marysville, California, United States, 95901
        • Fremont - Rideout Cancer Center
      • Modesto, California, United States, 95356
        • Kaiser Permanente-Modesto
      • Oakland, California, United States, 94611
        • Kaiser Permanente-Oakland
      • Oakland, California, United States, 94611
        • Kaiser Permanente Oakland-Broadway
      • Palo Alto, California, United States, 94304
        • Stanford Cancer Institute Palo Alto
      • Rancho Cordova, California, United States, 95670
        • Kaiser Permanente-Rancho Cordova Cancer Center
      • Redwood City, California, United States, 94063
        • Kaiser Permanente-Redwood City
      • Richmond, California, United States, 94801
        • Kaiser Permanente-Richmond
      • Rohnert Park, California, United States, 94928
        • Rohnert Park Cancer Center
      • Roseville, California, United States, 95678
        • The Permanente Medical Group-Roseville Radiation Oncology
      • Roseville, California, United States, 95661
        • Kaiser Permanente-Roseville
      • Sacramento, California, United States, 95817
        • University of California Davis Comprehensive Cancer Center
      • Sacramento, California, United States, 95814
        • Kaiser Permanente Downtown Commons
      • Sacramento, California, United States, 95823
        • Kaiser Permanente-South Sacramento
      • Sacramento, California, United States, 95823
        • South Sacramento Cancer Center
      • Sacramento, California, United States, 95825
        • Kaiser Permanente - Sacramento
      • San Francisco, California, United States, 94115
        • Kaiser Permanente-San Francisco
      • 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 Rafael, California, United States, 94903
        • Kaiser San Rafael-Gallinas
      • San Rafael, California, United States, 94903
        • Kaiser Permanente-San Rafael
      • Santa Clara, California, United States, 95051
        • Kaiser Permanente Medical Center - Santa Clara
      • Santa Rosa, California, United States, 95403
        • Kaiser Permanente-Santa Rosa
      • South San Francisco, California, United States, 94080
        • Kaiser Permanente Cancer Treatment Center
      • South San Francisco, California, United States, 94080
        • Kaiser Permanente-South San Francisco
      • Stockton, California, United States, 95210
        • Kaiser Permanente-Stockton
      • Truckee, California, United States, 96161
        • Gene Upshaw Memorial Tahoe Forest Cancer Center
      • Vacaville, California, United States, 95688
        • Kaiser Permanente Medical Center-Vacaville
      • Vallejo, California, United States, 94589
        • Kaiser Permanente-Vallejo
      • Walnut Creek, California, United States, 94596
        • Kaiser Permanente-Walnut Creek
    • Colorado
      • Aurora, Colorado, United States, 80012
        • Rocky Mountain Cancer Centers-Aurora
      • Boulder, Colorado, United States, 80301
        • Boulder Community 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, 80210
        • Porter Adventist Hospital
      • Denver, Colorado, United States, 80205
        • Kaiser Permanente-Franklin
      • 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, 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, 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
      • Fort Collins, Colorado, United States, 80524
        • Poudre Valley Hospital
      • Golden, Colorado, United States, 80401
        • Mountain Blue Cancer Care Center
      • 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
      • Lafayette, Colorado, United States, 80026
        • Kaiser Permanente-Rock Creek
      • 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
        • Kaiser Permanente-Lone Tree
      • 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
      • Parker, Colorado, United States, 80138
        • Rocky Mountain Cancer Centers-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
      • Thornton, Colorado, United States, 80260
        • National Jewish Health-Northern Hematology Oncology
      • Wheat Ridge, Colorado, United States, 80033
        • SCL Health Lutheran Medical 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, 32224-9980
        • Mayo Clinic in Florida
      • Lakeland, Florida, United States, 33805
        • The Watson Clinic
      • Pensacola, Florida, United States, 32504
        • Sacred Heart Hospital
      • Tampa, Florida, United States, 33612
        • Moffitt Cancer Center
    • Georgia
      • Columbus, Georgia, United States, 31904
        • John B Amos Cancer Center
    • 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
      • 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 Luke's Cancer Institute - Nampa
      • Nampa, Idaho, United States, 83687
        • Saint Alphonsus Cancer Care Center-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
      • Aurora, Illinois, United States, 60504
        • Rush - Copley Medical Center
      • Bloomington, Illinois, United States, 61704
        • Illinois CancerCare-Bloomington
      • 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
      • 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
      • Eureka, Illinois, United States, 61530
        • Illinois CancerCare-Eureka
      • Galesburg, Illinois, United States, 61401
        • Western Illinois Cancer Treatment Center
      • Galesburg, Illinois, United States, 61401
        • Illinois CancerCare-Galesburg
      • Harvey, Illinois, United States, 60426
        • Ingalls Memorial Hospital
      • Hines, Illinois, United States, 60141
        • Edward Hines Jr VA Hospital
      • Kewanee, Illinois, United States, 61443
        • Illinois CancerCare-Kewanee Clinic
      • 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
      • O'Fallon, Illinois, United States, 62269
        • Cancer Care Center of O'Fallon
      • Ottawa, Illinois, United States, 61350
        • Illinois CancerCare-Ottawa Clinic
      • 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
      • Rockford, Illinois, United States, 61114
        • SwedishAmerican Regional Cancer Center/ACT
      • 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
      • Yorkville, Illinois, United States, 60560
        • Rush-Copley Healthcare Center
    • Indiana
      • Fort Wayne, Indiana, United States, 46805
        • Parkview Hospital Randallia
      • Fort Wayne, Indiana, United States, 46845
        • Parkview Regional Medical Center
      • Indianapolis, Indiana, United States, 46202
        • Indiana University/Melvin and Bren Simon Cancer Center
      • Indianapolis, Indiana, United States, 46202
        • Sidney and Lois Eskenazi Hospital
      • Richmond, Indiana, United States, 47374
        • Reid Health
    • 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
        • 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
        • Trinity Regional Medical Center
      • 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
      • 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
      • 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
      • Overland Park, Kansas, United States, 66209
        • Menorah Medical Center
      • 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, 67214
        • Wesley Medical 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
      • 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
      • Shepherdsville, Kentucky, United States, 40165
        • Jewish Hospital Medical Center South
    • Louisiana
      • Baton Rouge, Louisiana, United States, 70809
        • Ochsner Health Center-Summa
      • Baton Rouge, Louisiana, United States, 70816
        • Medical Center of Baton Rouge
      • New Orleans, Louisiana, United States, 70121
        • Ochsner Medical Center Jefferson
    • Maine
      • Augusta, Maine, United States, 04330
        • Harold Alfond Center for Cancer Care
      • Bangor, Maine, United States, 04401
        • Eastern Maine Medical Center
      • Belfast, Maine, United States, 04915
        • Waldo County General Hospital
      • Biddeford, Maine, United States, 04005
        • MaineHealth/SMHC Cancer Care and Blood Disorders-Biddeford
      • Brewer, Maine, United States, 04412
        • Lafayette Family Cancer Center-EMMC
      • Rockport, Maine, United States, 04856
        • Penobscot Bay Medical Center
      • Sanford, Maine, United States, 04073
        • MaineHealth/SMHC Cancer Care and Blood Disorders-Sanford
    • Massachusetts
      • Springfield, Massachusetts, United States, 01199
        • Baystate Medical Center
      • Springfield, Massachusetts, United States, 01104
        • Mercy Medical Center
    • Michigan
      • Ann Arbor, Michigan, United States, 48106
        • Saint Joseph Mercy Hospital
      • Brighton, Michigan, United States, 48114
        • Saint Joseph Mercy Brighton
      • Brighton, Michigan, United States, 48114
        • Trinity Health IHA Medical Group Hematology Oncology - Brighton
      • Brownstown, Michigan, United States, 48183
        • Henry Ford Cancer Institute-Downriver
      • Canton, Michigan, United States, 48188
        • Saint Joseph Mercy Canton
      • Canton, Michigan, United States, 48188
        • Trinity Health IHA Medical Group Hematology Oncology - Canton
      • Caro, Michigan, United States, 48723
        • Caro Cancer Center
      • Chelsea, Michigan, United States, 48118
        • Saint Joseph Mercy Chelsea
      • Chelsea, Michigan, United States, 48118
        • Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital
      • Clarkston, Michigan, United States, 48346
        • Hematology Oncology Consultants-Clarkston
      • Clarkston, Michigan, United States, 48346
        • Newland Medical Associates-Clarkston
      • Clinton Township, Michigan, United States, 48038
        • Henry Ford Macomb Hospital-Clinton Township
      • Dearborn, Michigan, United States, 48126
        • Henry Ford Medical Center-Fairlane
      • Detroit, Michigan, United States, 48202
        • Henry Ford Hospital
      • Detroit, Michigan, United States, 48201
        • Wayne State University/Karmanos Cancer Institute
      • Detroit, Michigan, United States, 48236
        • Ascension Saint John Hospital
      • East China Township, Michigan, United States, 48054
        • Great Lakes Cancer Management Specialists-Doctors Park
      • Escanaba, Michigan, United States, 49829
        • Green Bay Oncology - Escanaba
      • Farmington Hills, Michigan, United States, 48334
        • Weisberg Cancer Treatment Center
      • Flint, Michigan, United States, 48503
        • Hurley Medical Center
      • Flint, Michigan, United States, 48503
        • Genesee Cancer and Blood Disease Treatment Center
      • Flint, Michigan, United States, 48503
        • Genesee Hematology Oncology PC
      • Flint, Michigan, United States, 48503
        • Genesys Hurley Cancer Institute
      • Grosse Pointe Woods, Michigan, United States, 48236
        • Academic Hematology Oncology Specialists
      • Grosse Pointe Woods, Michigan, United States, 48236
        • Great Lakes Cancer Management Specialists-Van Elslander Cancer Center
      • Grosse Pointe Woods, Michigan, United States, 48236
        • Michigan Breast Specialists-Grosse Pointe Woods
      • Jackson, Michigan, United States, 49201
        • Allegiance Health
      • Lansing, Michigan, United States, 48912
        • Sparrow Hospital
      • Livonia, Michigan, United States, 48154
        • Trinity Health Saint Mary Mercy Livonia Hospital
      • Livonia, Michigan, United States, 48154
        • Hope Cancer Clinic
      • Macomb, Michigan, United States, 48044
        • Great Lakes Cancer Management Specialists-Macomb Medical Campus
      • Macomb, Michigan, United States, 48044
        • Michigan Breast Specialists-Macomb Township
      • Marlette, Michigan, United States, 48453
        • Saint Mary's Oncology/Hematology Associates of Marlette
      • Midland, Michigan, United States, 48670
        • MyMichigan Medical Center Midland
      • Novi, Michigan, United States, 48377
        • Henry Ford Medical Center-Columbus
      • Pontiac, Michigan, United States, 48341
        • Saint Joseph Mercy Oakland
      • Pontiac, Michigan, United States, 48341
        • 21st Century Oncology-Pontiac
      • Pontiac, Michigan, United States, 48341
        • Hope Cancer Center
      • Pontiac, Michigan, United States, 48341
        • Newland Medical Associates-Pontiac
      • Rochester Hills, Michigan, United States, 48309
        • Great Lakes Cancer Management Specialists-Rochester Hills
      • Saginaw, Michigan, United States, 48601
        • Ascension Saint Mary's Hospital
      • Saginaw, Michigan, United States, 48604
        • Oncology Hematology Associates of Saginaw Valley PC
      • Sterling Heights, Michigan, United States, 48312
        • Bhadresh Nayak MD PC-Sterling Heights
      • Tawas City, Michigan, United States, 48764
        • Ascension Saint Joseph Hospital
      • Warren, Michigan, United States, 48093
        • Saint John Macomb-Oakland Hospital
      • Warren, Michigan, United States, 48088
        • Advanced Breast Care Center PLLC
      • Warren, Michigan, United States, 48093
        • Great Lakes Cancer Management Specialists-Macomb Professional Building
      • Warren, Michigan, United States, 48093
        • Macomb Hematology Oncology PC
      • Warren, Michigan, United States, 48093
        • Michigan Breast Specialists-Warren
      • West Bloomfield, Michigan, United States, 48322
        • Henry Ford West Bloomfield Hospital
      • West Branch, Michigan, United States, 48661
        • Saint Mary's Oncology/Hematology Associates of West Branch
      • Ypsilanti, Michigan, United States, 48197
        • Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus
      • Ypsilanti, Michigan, United States, 48106
        • Huron Gastroenterology PC
    • 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
      • 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
      • 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
      • 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
      • New Ulm, Minnesota, United States, 56073
        • New Ulm Medical Center
      • Park Rapids, Minnesota, United States, 56470
        • Essentia Health - Park Rapids
      • 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
    • Mississippi
      • Oxford, Mississippi, United States, 38655
        • Baptist Memorial Hospital and Cancer Center-Oxford
      • Southhaven, Mississippi, United States, 38671
        • Baptist Memorial Hospital and Cancer Center-Desoto
    • 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
      • 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
        • 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, 64132
        • Research Medical Center
      • 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, 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
      • Helena, Montana, United States, 59601
        • Saint Peter's Community Hospital
      • 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
      • Kearney, Nebraska, United States, 68845
        • Heartland Hematology and Oncology
      • Lincoln, Nebraska, United States, 68510
        • Saint Elizabeth Regional 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, 68122
        • Hematology and Oncology Consultants PC
      • Papillion, Nebraska, United States, 68046
        • Midlands Community Hospital
    • New Jersey
      • Morristown, New Jersey, United States, 07960
        • Morristown Medical Center
      • Summit, New Jersey, United States, 07902
        • Overlook Hospital
    • New Mexico
      • Albuquerque, New Mexico, United States, 87102
        • University of New Mexico Cancer Center
      • Albuquerque, New Mexico, United States, 87102
        • Lovelace Medical Center-Saint Joseph Square
      • Albuquerque, New Mexico, United States, 87109
        • New Mexico Oncology Hematology Consultants
      • Albuquerque, New Mexico, United States, 87110
        • Presbyterian Kaseman Hospital
      • Rio Rancho, New Mexico, United States, 87124
        • Presbyterian Rust Medical Center/Jorgensen Cancer Center
    • New York
      • Rochester, New York, United States, 14642
        • University of Rochester
      • White Plains, New York, United States, 10601
        • Dickstein Cancer Treatment Center
    • North Carolina
      • Greenville, North Carolina, United States, 27834
        • East Carolina University
      • Hendersonville, North Carolina, United States, 28791
        • Margaret R Pardee Memorial Hospital
    • 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
      • Jamestown, North Dakota, United States, 58401
        • Essentia Health - Jamestown Clinic
    • Ohio
      • Beavercreek, Ohio, United States, 45431
        • Indu and Raj Soin Medical Center
      • Centerville, Ohio, United States, 45459
        • Miami Valley Hospital South
      • Centerville, Ohio, United States, 45459
        • Dayton Physicians LLC-Miami Valley South
      • Cincinnati, Ohio, United States, 45220
        • Good Samaritan Hospital - Cincinnati
      • Cincinnati, Ohio, United States, 45242
        • Bethesda North Hospital
      • 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, 44195
        • Cleveland Clinic Foundation
      • Cleveland, Ohio, United States, 44111
        • Cleveland Clinic Cancer Center/Fairview Hospital
      • Dayton, Ohio, United States, 45406
        • Good Samaritan Hospital - Dayton
      • Dayton, Ohio, United States, 45409
        • Miami Valley Hospital
      • Dayton, Ohio, United States, 45415
        • Dayton Physician LLC-Miami Valley Hospital North
      • Dayton, Ohio, United States, 45415
        • Miami Valley Hospital North
      • 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
      • Independence, Ohio, United States, 44131
        • Cleveland Clinic Cancer Center Independence
      • Kettering, Ohio, United States, 45429
        • Kettering Medical Center
      • Kettering, Ohio, United States, 45409
        • Greater Dayton Cancer Center
      • Kettering, Ohio, United States, 45420
        • First Dayton Cancer Care
      • Mansfield, Ohio, United States, 44906
        • Cleveland Clinic Cancer Center Mansfield
      • Mayfield Heights, Ohio, United States, 44124
        • Hillcrest Hospital Cancer Center
      • Sandusky, Ohio, United States, 44870
        • North Coast Cancer Care
      • Springfield, Ohio, United States, 45505
        • Springfield Regional Medical Center
      • Springfield, Ohio, United States, 45504
        • Springfield Regional Cancer Center
      • Strongsville, Ohio, United States, 44136
        • Cleveland Clinic Cancer Center Strongsville
      • Troy, Ohio, United States, 45373
        • Upper Valley Medical Center
      • Troy, Ohio, United States, 45373
        • Dayton Physicians LLC - Troy
      • Warrensville Heights, Ohio, United States, 44122
        • South Pointe Hospital
      • Wooster, Ohio, United States, 44691
        • Cleveland Clinic Wooster Family Health and Surgery Center
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73104
        • University of Oklahoma Health Sciences Center
      • Oklahoma City, Oklahoma, United States, 73120
        • Mercy Hospital Oklahoma City
      • Oklahoma City, Oklahoma, United States, 73109
        • Integris Southwest Medical Center
      • Oklahoma City, Oklahoma, United States, 73142
        • Integris Cancer Institute of Oklahoma
    • 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, 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
    • Pennsylvania
      • Abington, Pennsylvania, United States, 19001
        • Jefferson Abington Hospital
      • Allentown, Pennsylvania, United States, 18103
        • Lehigh Valley Hospital-Cedar Crest
      • Bethlehem, Pennsylvania, United States, 18017
        • Lehigh Valley Hospital - Muhlenberg
      • Chadds Ford, Pennsylvania, United States, 19317
        • Christiana Care Health System-Concord Health Center
      • East Stroudsburg, Pennsylvania, United States, 18301
        • Pocono Medical Center
      • Ephrata, Pennsylvania, United States, 17522
        • Ephrata Cancer Center
      • Ephrata, Pennsylvania, United States, 17522
        • Ephrata Community Hospital
      • Gettysburg, Pennsylvania, United States, 17325
        • Adams Cancer Center
      • Hanover, Pennsylvania, United States, 17331
        • Cherry Tree Cancer Center
      • Hazleton, Pennsylvania, United States, 18201
        • Lehigh Valley Hospital-Hazleton
      • Lebanon, Pennsylvania, United States, 17042
        • Sechler Family Cancer Center
      • Philadelphia, Pennsylvania, United States, 19104
        • University of Pennsylvania/Abramson Cancer Center
      • Pittsburgh, Pennsylvania, United States, 15232
        • University of Pittsburgh Cancer Institute (UPCI)
      • Reading, Pennsylvania, United States, 19605
        • Penn State Health Saint Joseph Medical Center
      • Willow Grove, Pennsylvania, United States, 19090
        • Asplundh Cancer Pavilion
      • York, Pennsylvania, United States, 17403
        • WellSpan Health-York Cancer Center
      • York, Pennsylvania, United States, 17403
        • WellSpan Health-York Hospital
    • South Carolina
      • Boiling Springs, South Carolina, United States, 29316
        • Prisma Health Cancer Institute - Spartanburg
      • Clinton, South Carolina, United States, 29325
        • Prisma Health Cancer Institute - Laurens
      • 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
      • Greenville, South Carolina, United States, 29605
        • Prisma Health Greenville Memorial Hospital
      • 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, 57117-5134
        • Sanford USD Medical Center - Sioux Falls
      • Sioux Falls, South Dakota, United States, 57104
        • Sanford Cancer Center Oncology Clinic
    • Tennessee
      • Chattanooga, Tennessee, United States, 37404
        • Memorial Hospital
      • Hixson, Tennessee, United States, 37343
        • Pulmonary Medicine Center of Chattanooga-Hixson
      • Memphis, Tennessee, United States, 38120
        • Baptist Memorial Hospital and Cancer Center-Memphis
      • Ooltewah, Tennessee, United States, 37363
        • Memorial GYN Plus
    • Texas
      • Bryan, Texas, United States, 77802
        • Saint Joseph Regional Cancer Center
      • Lubbock, Texas, United States, 79410
        • Covenant Medical Center-Lakeside
    • Virginia
      • Richmond, Virginia, United States, 23298
        • Virginia Commonwealth University/Massey Cancer Center
    • Washington
      • Aberdeen, Washington, United States, 98520
        • Providence Regional Cancer System-Aberdeen
      • 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
      • 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
      • Poulsbo, Washington, United States, 98370
        • Harrison HealthPartners Hematology and Oncology-Poulsbo
      • Seattle, Washington, United States, 98107
        • Swedish Medical Center-Ballard Campus
      • Seattle, Washington, United States, 98122
        • Swedish Medical Center-First Hill
      • Seattle, Washington, United States, 98112
        • Kaiser Permanente Washington
      • 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
        • Northwest Medical Specialties PLLC
      • 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
    • West Virginia
      • Huntington, West Virginia, United States, 25701
        • Edwards Comprehensive Cancer Center
    • Wisconsin
      • Ashland, Wisconsin, United States, 54806
        • Duluth Clinic Ashland
      • Ashland, Wisconsin, United States, 54806
        • Northwest Wisconsin Cancer 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
      • La Crosse, Wisconsin, United States, 54601
        • Gundersen Lutheran Medical Center
      • Madison, Wisconsin, United States, 53792
        • University of Wisconsin Carbone Cancer Center
      • Manitowoc, Wisconsin, United States, 54221
        • Holy Family Memorial Hospital
      • Marinette, Wisconsin, United States, 54143
        • Saint Vincent Hospital Cancer Center at Marinette
      • Milwaukee, Wisconsin, United States, 53226
        • Medical College of Wisconsin
      • New Richmond, Wisconsin, United States, 54017
        • Cancer Center of Western Wisconsin
      • Oconto Falls, Wisconsin, United States, 54154
        • Saint Vincent Hospital Cancer Center at Oconto Falls
      • Sheboygan, Wisconsin, United States, 53081
        • HSHS Saint Nicholas Hospital
      • Sturgeon Bay, Wisconsin, United States, 54235-1495
        • Saint Vincent Hospital Cancer Center at Sturgeon Bay
    • 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

60 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • REGISTRATION STEP 1-SPECIMEN SUBMISSION
  • Patients must be suspected to have previously untreated acute myelogenous leukemia (AML) or myelodysplastic syndrome with excess blasts-2 (MDS-EB-2)
  • Patients must not be known to have AML in the central nervous system (CNS)
  • Patients must have specimens submitted for FLT3 testing for randomization stratification; collection of pretreatment specimens must be completed within 1 day of registration to Step 1; specimens must be submitted via the Southwest Oncology Group (SWOG) Specimen Tracking System; FLT3 results will be used for stratification purposes at the time of randomization; E-mail notification of randomization assignment must be received prior to Step 2 registration
  • Patients must be offered participation in specimen banking; with patient consent, pretreatment specimens must be collected and submitted via the SWOG Specimen Tracking System
  • Patients who have received prior therapy with midostaurin, any anti-PD-1 or anti-PD-L1 therapy, any deoxyribonucleic acid (DNA)-methyltransferase inhibitor (including hypomethylating agents such as azacitidine, decitabine, or other investigational agent that acts by inhibiting DNA or ribonucleic acid [RNA] methylation) for any condition, or prior intensive cytotoxic therapy for myelodysplastic syndrome (MDS), are not eligible
  • Patients must be able to swallow oral medications without crushing or chewing

  • Prior malignancy is allowed providing it does not require concurrent therapy

    • Exception: active hormonal therapy is allowed

  • Patients must not be pregnant or nursing; women/men of reproductive potential must have agreed to use an effective contraceptive method; a woman is considered to be of "reproductive potential" if she has had menses at any time in the preceding 12 consecutive months; in addition to routine contraceptive methods, "effective contraception also includes (but is not limited to) heterosexual celibacy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) defined as a hysterectomy, bilateral oophorectomy, bilateral tubal ligation, or vasectomy; however, if at any point a previously celibate patient chooses to become heterosexually active during the time period for use of contraceptive measures outlined in the protocol, he/she is responsible for beginning contraceptive measures

    • Women must agree to avoid breast-feeding and women of child-bearing potential (WOCBP) must agree to use highly effective contraception while receiving study drug and for a period of 31 weeks after the last dose of study drug; sexually-active men must agree to use a condom while receiving study drug and for 31 weeks after the last dose of study drug; vasectomized men must also agree to use a condom to avoid delivering drug in the seminal fluid
  • Patients must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines
  • As a part of the Oncology Patient Enrollment Network (OPEN) registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system
  • REGISTRATION STEP 2-RANDOMIZATION: Patients must be registered to Step 2 no more than 42 days after registration to Step 1 and no more than 42 days after collection of specimens for FLT3 testing

  • REGISTRATION STEP 2-RANDOMIZATION: Patients must have morphologically confirmed, previously untreated acute myeloid leukemia (AML) or MDS with excess blasts-2 (MDS-EB-2)

    • Patients with acute promyelocytic leukemia (APL), biphenotypic leukemia, blastic transformation of chronic myelogenous leukemia (CML or BCR/ABL), are not eligible
    • Patients must have disease present in the blood or bone marrow; patients with only extramedullary disease in the absence of bone marrow or blood involvement are not eligible
    • All tests for establishing baseline disease status eligibility must be based on blood and/or bone marrow examination performed within 42 days prior to randomization (registration Step 2)
  • REGISTRATION STEP 2-RANDOMIZATION: Patients must not be known to have AML in the CNS
  • REGISTRATION STEP 2-RANDOMIZATION: Patients must be deemed, in the judgment of the treating physician, to be ineligible for intensive induction therapy, or must have refused intensive induction therapy; rationale for clinical determination or notation of patient decision must be made
  • REGISTRATION STEP 2-RANDOMIZATION: Pretreatment cytogenetics must be performed on all patients; collection of pretreatment specimens must be completed within 42 days prior to randomization (registration Step 2); reports of the results must be submitted
  • REGISTRATION STEP 2-RANDOMIZATION: FLT3 results will be used for stratification purposes at the time of randomization; E-mail notification that FLT3 specimens have been processed must be received prior to randomization (registration Step 2)
  • REGISTRATION STEP 2-RANDOMIZATION: Prior treatment with hydroxyurea is permitted; prior all-trans retinoic acid (ATRA) for suspected APL and prior intrathecal therapy are permitted, but must plan to be discontinued prior to initiating protocol therapy; patients with signs/symptoms of hyperleukocytosis or white blood cells (WBC) >= 50,000/mcL can be treated with leukapheresis prior to randomization (registration to Step 2)
  • REGISTRATION STEP 2-RANDOMIZATION: Patients may have received non-intensive therapy for antecedent hematologic disorders, including lenalidomide; patients may have received prior chemotherapy for prior cancers; these therapies must be discontinued at least 5 days prior to randomization (registration to Step 2)
  • REGISTRATION STEP 2-RANDOMIZATION: Patients who are transfusion-dependent and patients receiving growth factor support are eligible; patients must discontinue growth factor support prior to initiation of protocol therapy

  • REGISTRATION STEP 2-RANDOMIZATION: The following tests must be performed within 14 days prior to randomization (registration to Step 2) to establish baseline values:

    • Performance status
    • Complete blood count (CBC)/differential/platelets
    • Creatinine clearance (Cockcroft-Gault)
    • Total bilirubin
    • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT)
    • Lactate dehydrogenase (LDH)
    • Albumin
    • Glucose
    • Fibrinogen
    • Electrocardiogram (ECG)
  • REGISTRATION STEP 2-RANDOMIZATION: Patients must have complete history and physical examination within 28 days prior to randomization (registration to Step 2); history must include autoimmune disease status (to determine whether patient is eligible for Arm B)
  • REGISTRATION STEP 2-RANDOMIZATION: Patients must not have active infection (systemic bacterial, fungal, or viral infection) that is not controlled (defined as exhibiting ongoing signs/symptoms related to the infection and without improvement despite appropriate antibiotics or other treatment)
  • REGISTRATION STEP 2-RANDOMIZATION: Patients must be eligible for at least one of the currently active investigational treatment arms (S1612B or S1612C); if the patient does not meet eligibility criteria for at least one active investigational arm, then the patient is not eligible for S1612
  • REGISTRATION STEP 2-RANDOMIZATION: Patients must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines
  • ARM B (AZACITIDINE + NIVOLUMAB)
  • Patients must not have active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs); replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment
  • Patients must have AST and ALT =< 2.5 x institutional upper limit of normal (IULN)
  • Patients must have total bilirubin =< 1.5 x IULN
  • Patients must have baseline troponin test performed for eligibility; however, no associated values must be met in order for the patient to be eligible
  • ARM C (AZACITIDINE + MIDOSTAURIN)
  • Patients must have total bilirubin =< 2.5 x IULN
  • Patients must have creatinine clearance =< 2.5 x IULN
  • Patients must have corrected QT (QTc) interval < 500/msec (by Bazett's formula) on baseline ECG
  • Patients must not have any history of hypersensitivity to any drugs or metabolites of midostaurin
  • All tests for establishing baseline values must be completed within 14 days prior to registration to Step 2 (randomization)

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
Active Comparator: Arm A (azacitidine)
Patients receive azacitidine SC or IV daily on days 1-7 or on an interrupted schedule which ensures that all 7 days of therapy are received within a 12 day period. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Other: Laboratory Biomarker Analysis
Correlative studies
Drug: Azacitidine
Given SC or IV
Other Names:
  • 5 AZC
  • 5-AC
  • 5-Azacytidine
  • 5-AZC
  • Azacytidine
  • Azacytidine, 5-
  • Ladakamycin
  • Mylosar
  • U-18496
  • Vidaza
  • 5-Azacitidine
Experimental: Arm B (azacitidine, nivolumab)
Patients receive azacitidine as in Arm A and nivolumab IV over 30-60 minutes on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Other: Laboratory Biomarker Analysis
Correlative studies
Biological: Nivolumab
Given IV
Other Names:
  • BMS-936558
  • MDX-1106
  • NIVO
  • ONO-4538
  • Opdivo
  • CMAB819
  • Nivolumab Biosimilar CMAB819
  • ABP 206
  • Nivolumab Biosimilar ABP 206
Drug: Azacitidine
Given SC or IV
Other Names:
  • 5 AZC
  • 5-AC
  • 5-Azacytidine
  • 5-AZC
  • Azacytidine
  • Azacytidine, 5-
  • Ladakamycin
  • Mylosar
  • U-18496
  • Vidaza
  • 5-Azacitidine
Experimental: Arm C (azacitidine, midostaurin)
Patients receive azacitidine as in Arm A and midostaurin orally (PO) twice daily (BID) on days 8-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Other: Laboratory Biomarker Analysis
Correlative studies
Drug: Azacitidine
Given SC or IV
Other Names:
  • 5 AZC
  • 5-AC
  • 5-Azacytidine
  • 5-AZC
  • Azacytidine
  • Azacytidine, 5-
  • Ladakamycin
  • Mylosar
  • U-18496
  • Vidaza
  • 5-Azacitidine
Drug: Midostaurin
Given PO
Other Names:
  • Rydapt
  • PKC412
  • CGP 41251
  • CGP41251
  • N-Benzoyl-Staurosporine
  • N-Benzoylstaurosporine
  • PKC-412
Experimental: Arm D (decitabine, cytarabine)

INDUCTION: Patients receive decitabine IV over 2 hours on days 1-5 and cytarabine IV continuously on days 6-11. Treatment repeats every 28 days for up to 2 courses in the absence of disease progression or unacceptable toxicity.

MAINTENANCE: Patients deemed stable at the discretion of the treating physician receive decitabine as in Induction. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Other: Laboratory Biomarker Analysis
Correlative studies
Drug: Decitabine
Given IV
Other Names:
  • 5-Aza-2'-deoxycytidine
  • Dacogen
  • Decitabine for Injection
  • Deoxyazacytidine
  • Dezocitidine
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
  • Beta-Cytosine Arabinoside
  • CHX-3311
  • Cytarabinum
  • Cytarbel
  • Cytosar
  • Cytosine Arabinoside
  • Cytosine-.beta.-arabinoside
  • Cytosine-beta-arabinoside
  • Erpalfa
  • Starasid
  • Tarabine PFS
  • U 19920
  • U-19920
  • Udicil
  • WR-28453

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall survival (OS) (Phase II)
Time Frame: Day of registration on study until death from any cause, assessed for up to 5 years
A stratified log-rank test of the null hypothesis (hazard ratio=1) with a one-sided alpha of 15% will be used to test an experimental arm versus azacitidine for further phase III testing.
Day of registration on study until death from any cause, assessed for up to 5 years
OS (Phase III)
Time Frame: Day of registration on study until death from any cause, assessed for up to 5 years
Will compare OS between the control arm and experimental arm(s) selected in the Phase II study. An efficacy test will be done using a stratified log-rank test with a one-sided alpha of 0.5%. A futility test will be done using a stratified log-rank test (modified to test the alternative HR) with a one-sided alpha of 1.0%. Each final test (stratified log-rank test of the null hypothesis) of an experimental arm versus azacitidine will be done with a two-sided alpha of 4.8%.
Day of registration on study until death from any cause, assessed for up to 5 years

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of adverse events graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0
Time Frame: Up to 5 years
Will estimate toxicity rates to within +/- 6% (95% confidence interval).
Up to 5 years
Remission rates
Time Frame: Up to 5 years
Will be tabulated.
Up to 5 years
OS
Time Frame: Day of registration on study until death from any cause, assessed for up to 5 years
Will be estimated using the Kaplan-Meier method or cumulative incident endpoints and associations. Will be assessed using Cox regression models (for cause-specific hazards as appropriate). Landmark analyses of different response categories will be evaluated based on dates at which 75% and 90% of patients have achieved a response (with other quantiles analyzed as needed).
Day of registration on study until death from any cause, assessed for up to 5 years
Relapse-free survival (RFS) defined as patients achieving complete remission (CR), or CR with incomplete hematological recovery (CRi)
Time Frame: Date of achievement of a remission until the date of relapse or death from any cause, assessed for up to 5 years
Will be estimated using the Kaplan-Meier method or cumulative incident endpoints and associations. Will be assessed using Cox regression models (for cause-specific hazards as appropriate). Landmark analyses of different response categories will be evaluated based on dates at which 75% and 90% of patients have achieved a response (with other quantiles analyzed as needed).
Date of achievement of a remission until the date of relapse or death from any cause, assessed for up to 5 years
Event-free survival (EFS)
Time Frame: Date of randomization to the first of: date of primary refractory disease; date of progressive disease; date off protocol therapy without CR or CRi; date of relapse from CR or CRi, or death from any cause, assessed for up to 5 years
Will be estimated using the Kaplan-Meier method or cumulative incident endpoints and associations. Will be assessed using Cox regression models (for cause-specific hazards as appropriate). Landmark analyses of different response categories will be evaluated based on dates at which 75% and 90% of patients have achieved a response (with other quantiles analyzed as needed).
Date of randomization to the first of: date of primary refractory disease; date of progressive disease; date off protocol therapy without CR or CRi; date of relapse from CR or CRi, or death from any cause, assessed for up to 5 years
Cumulative incidence of relapse defined as achieving CR or CRi
Time Frame: Date of achievement of a remission until the date of relapse or death, assessed for up to 5 years
Will be estimated using the Kaplan-Meier method or cumulative incident endpoints and associations. Will be assessed using Cox regression models (for cause-specific hazards as appropriate). Landmark analyses of different response categories will be evaluated based on dates at which 75% and 90% of patients have achieved a response (with other quantiles analyzed as needed).
Date of achievement of a remission until the date of relapse or death, assessed for up to 5 years
FLT3-ITD
Time Frame: Up to 5 years
The prognostic effect of FLT3-ITD (positive versus negative or non-evaluable) with respect to the outcome OS will be evaluated using Cox regression models. The predictive effect of FLT3-ITD (positive versus negative/non-evaluable) with respect to the outcome of OS and the treatments of azacitdine+midostaurin versus azacitidine will be evaluated using a Cox regression model with treatment arm and FLT3-ITD as covariates and including the interaction between the two covariates.
Up to 5 years
Cytogenetic abnormalities, risk categories, and mutations in bone marrow
Time Frame: Up to 5 years
Univariate and multivariable regression models will be used assess potential associations between outcomes (CR, OS, EFS, and RFS) and cytogenetic abnormalities and mutation status (including FLT3-ITD). Regression models including interaction terms with treatment arm will be fit. In addition to analyzing FLT3-ITD as categorical variable used in randomization stratification, we will analyze FLT3-TKD also and evaluate FLT3-ITD allelic ratio as a quantitative variable and as a binary variable using the threshold of 0.50.
Up to 5 years
Potential control arm drift
Time Frame: Up to 5 years
Only concurrently randomized patients will be evaluated in comparisons between arms.
Up to 5 years

Collaborators and Investigators

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

Sponsor

National Cancer Institute (NCI)

Investigators

  • Principal Investigator: Laura C Michaelis, SWOG Cancer Research Network

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)

February 2, 2018

Primary Completion (Actual)

August 1, 2023

Study Completion (Estimated)

October 29, 2024

Study Registration Dates

First Submitted

March 23, 2017

First Submitted That Met QC Criteria

March 23, 2017

First Posted (Actual)

March 28, 2017

Study Record Updates

Last Update Posted (Actual)

November 8, 2023

Last Update Submitted That Met QC Criteria

November 7, 2023

Last Verified

October 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NCI-2017-00436 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
  • U10CA180888 (U.S. NIH Grant/Contract)
  • S1612 (Other Identifier: CTEP)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

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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