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
Acute Myeloid Leukemia, Myelodysplastic Syndrome, Myelodysplastic Syndrome/Acute Myeloid Leukemia
About this trial
This is an interventional treatment trial for Acute Myeloid Leukemia
Eligibility Criteria
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)
Sites / Locations
- Anchorage Associates in Radiation Medicine
- Alaska Breast Care and Surgery LLC
- Alaska Oncology and Hematology LLC
- Alaska Women's Cancer Care
- Anchorage Oncology Centre
- Katmai Oncology Group
- Providence Alaska Medical Center
- University of Arizona Cancer Center-Orange Grove Campus
- Banner University Medical Center - Tucson
- University of Arizona Cancer Center-North Campus
- CHI Saint Vincent Cancer Center Hot Springs
- John L McClellan Memorial Veterans Hospital
- Kaiser Permanente-Deer Valley Medical Center
- Providence Saint Joseph Medical Center/Disney Family Cancer Center
- Kaiser Permanente-Fremont
- Fresno Cancer Center
- Kaiser Permanente-Fresno
- Fremont - Rideout Cancer Center
- Kaiser Permanente-Modesto
- Kaiser Permanente Oakland-Broadway
- Kaiser Permanente-Oakland
- Stanford Cancer Institute Palo Alto
- Kaiser Permanente-Rancho Cordova Cancer Center
- Kaiser Permanente-Redwood City
- Kaiser Permanente-Richmond
- Rohnert Park Cancer Center
- Kaiser Permanente-Roseville
- The Permanente Medical Group-Roseville Radiation Oncology
- Kaiser Permanente Downtown Commons
- University of California Davis Comprehensive Cancer Center
- Kaiser Permanente-South Sacramento
- South Sacramento Cancer Center
- Kaiser Permanente - Sacramento
- Kaiser Permanente-San Francisco
- Kaiser Permanente-Santa Teresa-San Jose
- Stanford Cancer Center South Bay
- Kaiser Permanente San Leandro
- Kaiser Permanente-San Rafael
- Kaiser San Rafael-Gallinas
- Kaiser Permanente Medical Center - Santa Clara
- Kaiser Permanente-Santa Rosa
- Kaiser Permanente Cancer Treatment Center
- Kaiser Permanente-South San Francisco
- Kaiser Permanente-Stockton
- Gene Upshaw Memorial Tahoe Forest Cancer Center
- Kaiser Permanente Medical Center-Vacaville
- Kaiser Permanente-Vallejo
- Kaiser Permanente-Walnut Creek
- Rocky Mountain Cancer Centers-Aurora
- Boulder Community Hospital
- Rocky Mountain Cancer Centers-Boulder
- Penrose-Saint Francis Healthcare
- Rocky Mountain Cancer Centers-Penrose
- Denver Health Medical Center
- Kaiser Permanente-Franklin
- National Jewish Health-Main Campus
- The Women's Imaging Center
- Porter Adventist Hospital
- Colorado Blood Cancer Institute
- Presbyterian - Saint Lukes Medical Center - Health One
- Rocky Mountain Cancer Centers-Midtown
- SCL Health Saint Joseph Hospital
- Rocky Mountain Cancer Centers-Rose
- Western Surgical Care
- Mercy Medical Center
- Southwest Oncology PC
- Mountain Blue Cancer Care Center - Swedish
- Swedish Medical Center
- Poudre Valley Hospital
- Mountain Blue Cancer Care Center
- National Jewish Health-Western Hematology Oncology
- Saint Mary's Hospital and Regional Medical Center
- North Colorado Medical Center
- Good Samaritan Medical Center
- Kaiser Permanente-Rock Creek
- Rocky Mountain Cancer Centers-Lakewood
- Saint Anthony Hospital
- Rocky Mountain Cancer Centers-Littleton
- Littleton Adventist Hospital
- Kaiser Permanente-Lone Tree
- Rocky Mountain Cancer Centers-Sky Ridge
- Longmont United Hospital
- Rocky Mountain Cancer Centers-Longmont
- McKee Medical Center
- Parker Adventist Hospital
- Rocky Mountain Cancer Centers-Parker
- Saint Mary Corwin Medical Center
- Rocky Mountain Cancer Centers - Pueblo
- National Jewish Health-Northern Hematology Oncology
- Rocky Mountain Cancer Centers-Thornton
- SCL Health Lutheran Medical Center
- Beebe Medical Center
- Delaware Clinical and Laboratory Physicians PA
- Helen F Graham Cancer Center
- Medical Oncology Hematology Consultants PA
- Christiana Care Health System-Christiana Hospital
- Beebe Health Campus
- TidalHealth Nanticoke / Allen Cancer Center
- Christiana Care Health System-Wilmington Hospital
- Mayo Clinic in Florida
- The Watson Clinic
- Sacred Heart Hospital
- Moffitt Cancer Center
- John B Amos Cancer Center
- Kaiser Permanente Moanalua Medical Center
- Saint Alphonsus Cancer Care Center-Boise
- Saint Luke's Cancer Institute - Boise
- Saint Alphonsus Cancer Care Center-Caldwell
- Kootenai Health - Coeur d'Alene
- Walter Knox Memorial Hospital
- Saint Luke's Cancer Institute - Fruitland
- Idaho Urologic Institute-Meridian
- Saint Luke's Cancer Institute - Meridian
- Saint Luke's Cancer Institute - Nampa
- Saint Alphonsus Cancer Care Center-Nampa
- Kootenai Clinic Cancer Services - Post Falls
- Kootenai Cancer Clinic
- Saint Luke's Cancer Institute - Twin Falls
- Rush - Copley Medical Center
- Illinois CancerCare-Bloomington
- Illinois CancerCare-Canton
- Memorial Hospital of Carbondale
- SIH Cancer Institute
- Illinois CancerCare-Carthage
- Centralia Oncology Clinic
- Carle at The Riverfront
- Cancer Care Specialists of Illinois - Decatur
- Decatur Memorial Hospital
- Carle Physician Group-Effingham
- Crossroads Cancer Center
- Illinois CancerCare-Eureka
- Illinois CancerCare-Galesburg
- Western Illinois Cancer Treatment Center
- Ingalls Memorial Hospital
- Edward Hines Jr VA Hospital
- Illinois CancerCare-Kewanee Clinic
- Illinois CancerCare-Macomb
- Carle Physician Group-Mattoon/Charleston
- Loyola University Medical Center
- Marjorie Weinberg Cancer Center at Loyola-Gottlieb
- Good Samaritan Regional Health Center
- Cancer Care Center of O'Fallon
- Illinois CancerCare-Ottawa Clinic
- Illinois CancerCare-Pekin
- OSF Saint Francis Radiation Oncology at Pekin Cancer Treatment Center
- Illinois CancerCare-Peoria
- OSF Saint Francis Radiation Oncology at Peoria Cancer Center
- Methodist Medical Center of Illinois
- OSF Saint Francis Medical Center
- Illinois CancerCare-Peru
- Valley Radiation Oncology
- Illinois CancerCare-Princeton
- SwedishAmerican Regional Cancer Center/ACT
- Southern Illinois University School of Medicine
- Springfield Clinic
- Memorial Medical Center
- Southwest Illinois Health Services LLP
- Carle Cancer Center
- The Carle Foundation Hospital
- Rush-Copley Healthcare Center
- Parkview Hospital Randallia
- Parkview Regional Medical Center
- Indiana University/Melvin and Bren Simon Cancer Center
- Sidney and Lois Eskenazi Hospital
- Reid Health
- Mary Greeley Medical Center
- McFarland Clinic - Ames
- McFarland Clinic - Boone
- Medical Oncology and Hematology Associates-West Des Moines
- Mercy Cancer Center-West Lakes
- Alegent Health Mercy Hospital
- Greater Regional Medical Center
- Iowa Methodist Medical Center
- Medical Oncology and Hematology Associates-Des Moines
- Broadlawns Medical Center
- Mercy Medical Center - Des Moines
- Mission Cancer and Blood - Laurel
- Iowa Lutheran Hospital
- McFarland Clinic - Trinity Cancer Center
- Trinity Regional Medical Center
- McFarland Clinic - Jefferson
- McFarland Clinic - Marshalltown
- Methodist West Hospital
- Mercy Medical Center-West Lakes
- Central Care Cancer Center - Garden City
- Central Care Cancer Center - Great Bend
- Lawrence Memorial Hospital
- Kansas Institute of Medicine Cancer and Blood Center
- Minimally Invasive Surgery Hospital
- Menorah Medical Center
- Cancer Center of Kansas-Wichita Medical Arts Tower
- Ascension Via Christi Hospitals Wichita
- Cancer Center of Kansas - Wichita
- Wesley Medical Center
- Flaget Memorial Hospital
- Commonwealth Cancer Center-Corbin
- Saint Joseph Radiation Oncology Resource Center
- Saint Joseph Hospital East
- Saint Joseph London
- Jewish Hospital
- Saints Mary and Elizabeth Hospital
- UofL Health Medical Center Northeast
- Jewish Hospital Medical Center South
- Ochsner Health Center-Summa
- Medical Center of Baton Rouge
- Ochsner Medical Center Jefferson
- Harold Alfond Center for Cancer Care
- Eastern Maine Medical Center
- Waldo County General Hospital
- MaineHealth/SMHC Cancer Care and Blood Disorders-Biddeford
- Lafayette Family Cancer Center-EMMC
- Penobscot Bay Medical Center
- MaineHealth/SMHC Cancer Care and Blood Disorders-Sanford
- Mercy Medical Center
- Baystate Medical Center
- Saint Joseph Mercy Hospital
- Saint Joseph Mercy Brighton
- Trinity Health IHA Medical Group Hematology Oncology - Brighton
- Henry Ford Cancer Institute-Downriver
- Saint Joseph Mercy Canton
- Trinity Health IHA Medical Group Hematology Oncology - Canton
- Caro Cancer Center
- Saint Joseph Mercy Chelsea
- Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital
- Hematology Oncology Consultants-Clarkston
- Newland Medical Associates-Clarkston
- Henry Ford Macomb Hospital-Clinton Township
- Henry Ford Medical Center-Fairlane
- Wayne State University/Karmanos Cancer Institute
- Henry Ford Hospital
- Ascension Saint John Hospital
- Great Lakes Cancer Management Specialists-Doctors Park
- Green Bay Oncology - Escanaba
- Weisberg Cancer Treatment Center
- Genesee Cancer and Blood Disease Treatment Center
- Genesee Hematology Oncology PC
- Genesys Hurley Cancer Institute
- Hurley Medical Center
- Academic Hematology Oncology Specialists
- Great Lakes Cancer Management Specialists-Van Elslander Cancer Center
- Michigan Breast Specialists-Grosse Pointe Woods
- Allegiance Health
- Sparrow Hospital
- Hope Cancer Clinic
- Trinity Health Saint Mary Mercy Livonia Hospital
- Great Lakes Cancer Management Specialists-Macomb Medical Campus
- Michigan Breast Specialists-Macomb Township
- Saint Mary's Oncology/Hematology Associates of Marlette
- MyMichigan Medical Center Midland
- Henry Ford Medical Center-Columbus
- 21st Century Oncology-Pontiac
- Hope Cancer Center
- Newland Medical Associates-Pontiac
- Saint Joseph Mercy Oakland
- Great Lakes Cancer Management Specialists-Rochester Hills
- Ascension Saint Mary's Hospital
- Oncology Hematology Associates of Saginaw Valley PC
- Bhadresh Nayak MD PC-Sterling Heights
- Ascension Saint Joseph Hospital
- Advanced Breast Care Center PLLC
- Great Lakes Cancer Management Specialists-Macomb Professional Building
- Macomb Hematology Oncology PC
- Michigan Breast Specialists-Warren
- Saint John Macomb-Oakland Hospital
- Henry Ford West Bloomfield Hospital
- Saint Mary's Oncology/Hematology Associates of West Branch
- Huron Gastroenterology PC
- Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus
- Sanford Joe Lueken Cancer Center
- Essentia Health Saint Joseph's Medical Center
- Fairview Ridges Hospital
- Mercy Hospital
- Essentia Health - Deer River Clinic
- Essentia Health Saint Mary's - Detroit Lakes Clinic
- Essentia Health Cancer Center
- Essentia Health Saint Mary's Medical Center
- Miller-Dwan Hospital
- Fairview Southdale Hospital
- Lake Region Healthcare Corporation-Cancer Care
- Essentia Health - Fosston
- Unity Hospital
- Essentia Health Hibbing Clinic
- Fairview Clinics and Surgery Center Maple Grove
- Minnesota Oncology Hematology PA-Maplewood
- Saint John's Hospital - Healtheast
- Abbott-Northwestern Hospital
- Hennepin County Medical Center
- Health Partners Inc
- Monticello Cancer Center
- New Ulm Medical Center
- Essentia Health - Park Rapids
- North Memorial Medical Health Center
- Mayo Clinic in Rochester
- Park Nicollet Clinic - Saint Louis Park
- Regions Hospital
- United Hospital
- Essentia Health Sandstone
- Saint Francis Regional Medical Center
- Lakeview Hospital
- Sanford Thief River Falls Medical Center
- Essentia Health Virginia Clinic
- Ridgeview Medical Center
- Rice Memorial Hospital
- Minnesota Oncology Hematology PA-Woodbury
- Sanford Cancer Center Worthington
- Fairview Lakes Medical Center
- Baptist Memorial Hospital and Cancer Center-Oxford
- Baptist Memorial Hospital and Cancer Center-Desoto
- Saint Louis Cancer and Breast Institute-Ballwin
- Central Care Cancer Center - Bolivar
- Parkland Health Center-Bonne Terre
- Cox Cancer Center Branson
- Saint Francis Medical Center
- Southeast Cancer Center
- Siteman Cancer Center at West County Hospital
- Centerpoint Medical Center LLC
- Capital Region Southwest Campus
- Freeman Health System
- Mercy Hospital Joplin
- Research Medical Center
- Delbert Day Cancer Institute at PCRMC
- Mercy Clinic-Rolla-Cancer and Hematology
- Heartland Regional Medical Center
- Saint Louis Cancer and Breast Institute-South City
- Washington University School of Medicine
- Siteman Cancer Center-South County
- Missouri Baptist Medical Center
- Siteman Cancer Center at Christian Hospital
- Mercy Hospital Saint Louis
- Siteman Cancer Center at Saint Peters Hospital
- Sainte Genevieve County Memorial Hospital
- Mercy Hospital Springfield
- CoxHealth South Hospital
- Missouri Baptist Sullivan Hospital
- Missouri Baptist Outpatient Center-Sunset Hills
- Mercy Hospital Washington
- Community Hospital of Anaconda
- Billings Clinic Cancer Center
- Saint Vincent Healthcare
- Saint Vincent Frontier Cancer Center
- Bozeman Deaconess Hospital
- Saint James Community Hospital and Cancer Treatment Center
- Benefis Healthcare- Sletten Cancer Institute
- Great Falls Clinic
- Saint Peter's Community Hospital
- Kalispell Regional Medical Center
- Saint Patrick Hospital - Community Hospital
- Community Medical Hospital
- CHI Health Saint Francis
- Heartland Hematology and Oncology
- CHI Health Good Samaritan
- Saint Elizabeth Regional Medical Center
- Alegent Health Immanuel Medical Center
- Hematology and Oncology Consultants PC
- Alegent Health Bergan Mercy Medical Center
- Alegent Health Lakeside Hospital
- Creighton University Medical Center
- Midlands Community Hospital
- Morristown Medical Center
- Overlook Hospital
- Lovelace Medical Center-Saint Joseph Square
- University of New Mexico Cancer Center
- New Mexico Oncology Hematology Consultants
- Presbyterian Kaseman Hospital
- Presbyterian Rust Medical Center/Jorgensen Cancer Center
- University of Rochester
- Dickstein Cancer Treatment Center
- East Carolina University
- Margaret R Pardee Memorial Hospital
- Sanford Bismarck Medical Center
- Essentia Health Cancer Center-South University Clinic
- Sanford South University Medical Center
- Sanford Broadway Medical Center
- Sanford Roger Maris Cancer Center
- Essentia Health - Jamestown Clinic
- Indu and Raj Soin Medical Center
- Dayton Physicians LLC-Miami Valley South
- Miami Valley Hospital South
- Good Samaritan Hospital - Cincinnati
- Oncology Hematology Care Inc-Kenwood
- Bethesda North Hospital
- TriHealth Cancer Institute-Westside
- TriHealth Cancer Institute-Anderson
- Cleveland Clinic Cancer Center/Fairview Hospital
- Cleveland Clinic Foundation
- Good Samaritan Hospital - Dayton
- Miami Valley Hospital
- Dayton Physician LLC-Miami Valley Hospital North
- Miami Valley Hospital North
- Armes Family Cancer Center
- Blanchard Valley Hospital
- Orion Cancer Care
- Atrium Medical Center-Middletown Regional Hospital
- Dayton Physicians LLC-Atrium
- Dayton Physicians LLC-Wayne
- Wayne Hospital
- Cleveland Clinic Cancer Center Independence
- Greater Dayton Cancer Center
- First Dayton Cancer Care
- Kettering Medical Center
- Cleveland Clinic Cancer Center Mansfield
- Hillcrest Hospital Cancer Center
- North Coast Cancer Care
- Springfield Regional Cancer Center
- Springfield Regional Medical Center
- Cleveland Clinic Cancer Center Strongsville
- Dayton Physicians LLC - Troy
- Upper Valley Medical Center
- South Pointe Hospital
- Cleveland Clinic Wooster Family Health and Surgery Center
- University of Oklahoma Health Sciences Center
- Integris Southwest Medical Center
- Mercy Hospital Oklahoma City
- Integris Cancer Institute of Oklahoma
- Saint Alphonsus Medical Center-Baker City
- Saint Charles Health System
- Clackamas Radiation Oncology Center
- Providence Cancer Institute Clackamas Clinic
- Bay Area Hospital
- Providence Newberg Medical Center
- Saint Alphonsus Medical Center-Ontario
- Providence Portland Medical Center
- Providence Saint Vincent Medical Center
- Saint Charles Health System-Redmond
- Jefferson Abington Hospital
- Lehigh Valley Hospital-Cedar Crest
- Lehigh Valley Hospital - Muhlenberg
- Christiana Care Health System-Concord Health Center
- Pocono Medical Center
- Ephrata Cancer Center
- Ephrata Community Hospital
- Adams Cancer Center
- Cherry Tree Cancer Center
- Lehigh Valley Hospital-Hazleton
- Sechler Family Cancer Center
- University of Pennsylvania/Abramson Cancer Center
- University of Pittsburgh Cancer Institute (UPCI)
- Penn State Health Saint Joseph Medical Center
- Asplundh Cancer Pavilion
- WellSpan Health-York Cancer Center
- WellSpan Health-York Hospital
- Prisma Health Cancer Institute - Spartanburg
- Prisma Health Cancer Institute - Laurens
- Prisma Health Cancer Institute - Easley
- Prisma Health Cancer Institute - Butternut
- Prisma Health Cancer Institute - Faris
- Prisma Health Greenville Memorial Hospital
- Prisma Health Cancer Institute - Eastside
- Prisma Health Cancer Institute - Greer
- Prisma Health Cancer Institute - Seneca
- Sanford Cancer Center Oncology Clinic
- Sanford USD Medical Center - Sioux Falls
- Memorial Hospital
- Pulmonary Medicine Center of Chattanooga-Hixson
- Baptist Memorial Hospital and Cancer Center-Memphis
- Memorial GYN Plus
- Saint Joseph Regional Cancer Center
- Covenant Medical Center-Lakeside
- Virginia Commonwealth University/Massey Cancer Center
- Providence Regional Cancer System-Aberdeen
- PeaceHealth Saint Joseph Medical Center
- Harrison HealthPartners Hematology and Oncology-Bremerton
- Harrison Medical Center
- Highline Medical Center-Main Campus
- Providence Regional Cancer System-Centralia
- Swedish Cancer Institute-Edmonds
- Saint Elizabeth Hospital
- Providence Regional Cancer Partnership
- Saint Francis Hospital
- Swedish Cancer Institute-Issaquah
- Kadlec Clinic Hematology and Oncology
- Providence Regional Cancer System-Lacey
- Saint Clare Hospital
- PeaceHealth Saint John Medical Center
- Harrison HealthPartners Hematology and Oncology-Poulsbo
- Pacific Gynecology Specialists
- Swedish Medical Center-Ballard Campus
- Kaiser Permanente Washington
- Swedish Medical Center-Cherry Hill
- Swedish Medical Center-First Hill
- PeaceHealth United General Medical Center
- Providence Regional Cancer System-Shelton
- MultiCare Deaconess Cancer and Blood Specialty Center - Valley
- MultiCare Deaconess Cancer and Blood Specialty Center - Downtown
- MultiCare Deaconess Cancer and Blood Specialty Center - North
- Franciscan Research Center-Northwest Medical Plaza
- Northwest Medical Specialties PLLC
- PeaceHealth Southwest Medical Center
- Providence Saint Mary Regional Cancer Center
- Providence Regional Cancer System-Yelm
- Edwards Comprehensive Cancer Center
- Duluth Clinic Ashland
- Northwest Wisconsin Cancer Center
- Saint Vincent Hospital Cancer Center Green Bay
- Saint Vincent Hospital Cancer Center at Saint Mary's
- Gundersen Lutheran Medical Center
- University of Wisconsin Carbone Cancer Center
- Holy Family Memorial Hospital
- Saint Vincent Hospital Cancer Center at Marinette
- Medical College of Wisconsin
- Cancer Center of Western Wisconsin
- Saint Vincent Hospital Cancer Center at Oconto Falls
- HSHS Saint Nicholas Hospital
- Saint Vincent Hospital Cancer Center at Sturgeon Bay
- Cheyenne Regional Medical Center-West
- Billings Clinic-Cody
- Welch Cancer Center
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Active Comparator
Experimental
Experimental
Experimental
Arm A (azacitidine)
Arm B (azacitidine, nivolumab)
Arm C (azacitidine, midostaurin)
Arm D (decitabine, cytarabine)
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.
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.
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.
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.