Cytarabine and Daunorubicin Hydrochloride or Idarubicin and Cytarabine With or Without Vorinostat in Treating Younger Patients With Previously Untreated Acute Myeloid Leukemia

Acute Myeloid Leukemia Clinical Trial

Official title:

A Randomized Phase III Study of Standard Cytarabine Plus Daunorubicin (7+3) Therapy or Idarubicin With High Dose Cytarabine (IA) Versus IA With Vorinostat (NSC-701852) (IA + V) in Younger Patients With Previously Untreated Acute Myeloid Leukemia (AML)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01802333
• Other study ID #: NCI-2013-00490
• Secondary ID: NCI-2013-00490S1
• Status: Completed
• Phase: Phase 3
• Start date: February 12, 2013
• Est. completion date: June 15, 2017

Study information

• Verified date: November 2018
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This randomized phase III trial studies cytarabine and daunorubicin hydrochloride or idarubicin and cytarabine with or without vorinostat to see how well they work in treating younger patients with previously untreated acute myeloid leukemia. Drugs used in chemotherapy, such as cytarabine, daunorubicin hydrochloride, idarubicin, and vorinostat, work in different ways to stop the growth of cancer cells, either by killing the cells, stopping them from dividing, or by stopping from spreading. Giving more than one drug (combination chemotherapy) and giving the drugs in different doses and in different combinations may kill more cancer cells. It is not yet known which combination chemotherapy is more effective in treating acute myeloid leukemia.

Description:

PRIMARY OBJECTIVES:

I. To compare event-free survival (EFS) between patients with acute myeloid leukemia (AML) who receive standard 7+3 (cytarabine and daunorubicin hydrochloride) or idarubicin and high-dose cytarabine (IA) to patients who receive IA + vorinostat. (Chemotherapy) II. To determine whether it is possible to get 60% or more of adults with high-risk AML (by cytogenetics) in first complete remission (CR1) to allogeneic hematopoietic cell transplantation (HCT). (Transplant)

SECONDARY OBJECTIVES:

I. To estimate the frequency and severity of toxicities of the three regimens in this patient population. (Chemotherapy) II. To estimate disease-free survival (DFS) among patients who receive transplant. (Transplant) III. To compare event-free survival (EFS) between patients who receive standard 7 + 3 to patients who receive IA. (Chemotherapy) IV. To estimate the prevalence of the mutations nucleophosmin (nucleolar phosphoprotein B23, numatrin) (NPM1), isocitrate dehydrogenase 1 (NADP+), soluble (IDH1), isocitrate dehydrogenase 2 (NADP+), mitochondrial (IDH2), tet methylcytosine dioxygenase 2 (TET2) and deoxyribonucleic acid (DNA) (cytosine-5-)-methyltransferase 3 alpha (DNMT3A) and the cytogenetic risk distribution of patients on this study and to evaluate the association between these and overall survival (OS), event-free survival (EFS), disease-free survival (DFS), and complete remission rate. (Chemotherapy/Translational Medicine) V. To compare the complete response rate, disease-free survival (DFS), and overall survival (OS) between patients who receive standard 7+3 therapy or IA to patients who receive IA + vorinostat. (Chemotherapy)

TERTIARY OBJECTIVES:

I. Future planned studies will include testing of histone H3 acetylation, induction of gamma H2A histone family, member X (H2AX), analysis of reactive oxygen species (ROS) resistance and DNA methylation profiles. (Chemotherapy/Translational Medicine)

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

INDUCTION/RE-INDUCTION:

ARM I: Patients receive standard dose cytarabine intravenously (IV) continuously on days 1-7 and daunorubicin hydrochloride IV on days 1-3. Patients with residual blasts may receive re-induction treatment beginning on day 15. Patients achieving complete remission (CR) or complete remission with incomplete platelet recover (CRi) may proceed to allogeneic hematopoietic stem cell transplant (HSCT) or to consolidation therapy.

ARM II: Patients receive high dose cytarabine IV continuously on days 1-4 and idarubicin IV over 15 minutes on days 1-3. Patients with residual blasts may receive re-induction treatment beginning on day 28. Patients achieving CR or CRi may proceed to allogeneic HSCT or to consolidation therapy.

ARM III: Patients receive vorinostat orally (PO) thrice daily (TID) on days 1-3, high-dose cytarabine IV continuously on days 4-7, and idarubicin IV over 15 minutes on days 4-6. Patients with residual blasts may receive re-induction treatment beginning on day 28. Patients achieving CR or CRi may proceed to allogeneic HSCT or to consolidation therapy. (Permanently closed to accrual, effective 6/2/2015) Patient previously randomized to Arm III may continue treatment without vorinostat.

CONSOLIDATION:

ARM I: Patients receive cytarabine IV over 3 hours every 12 hours on days 1, 3, and 5.

ARM II: Patients receive cytarabine IV continuously on days 1-3 and idarubicin IV over 15 minutes on days 1-2.

ARM III: Patients receive vorinostat PO TID on days 1-3, cytarabine IV continuously on days 4-6, and idarubicin IV over 15 minutes on days 4-5. (Permanently closed to accrual, effective 6/2/2015) Patient previously randomized to Arm III may continue treatment with or without vorinostat.

In all arms, treatment repeats every 28 days for 4 courses or until transplant in the absence of disease progression or unacceptable toxicity.

TRANSPLANT: Patients may undergo an allogeneic transplant after induction therapy or consolidation therapy.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 754
• Est. completion date: June 15, 2017
• Est. primary completion date: June 15, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

Inclusion Criteria:

• STEP 1 - INDUCTION/RE-INDUCTION

• Patients must have morphologically confirmed newly diagnosed acute myelogenous leukemia (AML) with blood or bone marrow disease; patients with only extramedullary disease in the absence of bone marrow or blood involvement are not eligible; note: this protocol uses World Health Organization (WHO) diagnostic criteria for AML; patients with acute promyelocytic leukemia (APL, French-American-British [FAB], M3) or blastic transformation of chronic myelogenous leukemia (CML) are not eligible; patients with known core binding factor (CBF) or fms-like tyrosine kinase 3 (FLT3) related leukemias are eligible for this study, but should preferentially be placed on National Cancer Institute (NCI)-sponsored protocols specific for these subtypes, if available

• Patients must have diagnostic/pre-treatment specimens obtained within 28 days prior to registration submitted for cytogenetic (and fluorescent in situ hybridization [FISH] if possible) analysis to determine risk status; high risk classification will be defined as del(5q)/-5, del(7q)/-7, abn3q26 [inv(3)/t(3;3)], 11q23 rearrangement [except t(9;11)], 17p-, t(6;9), t(9;22), complex (at least 3 unrelated abnormalities [abn]), and monosomal karyotype (either loss of two different chromosomes or loss of one chromosome along with a structural chromosome abnormality other than add, ring and mar); karyograms and cytogenetics/FISH analysis reports must be submitted for discipline review

• Patients must be chemo-naïve, i.e., not have received any prior induction chemotherapy for AML or myelodysplastic syndrome (MDS); temporary prior measures such as apheresis or hydroxyurea are allowed; prior anthracycline therapy is allowed, but must not exceed a dose of 200 mg/m^2 daunorubicin or equivalent; prior all-trans retinoic acid (ATRA) for suspected APL is allowed; prior methotrexate for central nervous system (CNS) involvement is allowed; patients with prior history of MDS must not have received azacitidine, decitabine, lenalidomide or vorinostat

• Patients must have peripheral blood and bone marrow aspirate specimens obtained within 28 days prior to registration submitted for translational medicine; with patient consent, residuals will be banked for future research

• Patients must have Zubrod performance status =< 3

• Patients must have either echocardiogram (ECHO) or multi gated acquisition scan (MUGA) with ejection fraction >= 45% within 28 days prior to registration

• Patients must not have prolonged corrected QT (QTc) interval (> 500 msec) determined by electrocardiogram (EKG) within 28 days prior to registration

• Patients must not have cardiac disease defined as: New York Heart Association (NYHA) > class II; patients must not have unstable angina (angina symptoms at rest) or new onset angina (began within the last 3 months) or myocardial infarction within the past 6 months

• Patients must not have any coexisting medical condition that is likely to interfere with study procedures or results, and must be reasonable candidates for intensive chemotherapy, in the opinion of their treating physicians

• Patients who are known to be human immunodeficiency virus (HIV) positive (+) are eligible providing they meet all of the following additional criteria within 28 days prior to registration:

• Cluster of differentiation (CD) 4 cells >= 500/mm^3

• Viral load < 50 copies of HIV messenger ribonucleic acid (mRNA)/mm^3 if on combination antiretroviral therapy (cART) or < 25,000 copies of HIV mRNA if not on cART

• No zidovudine or stavudine as part of cART; patients who are HIV+ and do not meet all of these criteria are not eligible for this study

• Patients with known hepatitis B or hepatitis C infection may be eligible providing they have viral load < 800,000 IU/mL within 28 days prior to registration

• Patients must be able to take oral medications

• Patients must have a history and physical examination obtained within 28 days prior to registration

• 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 heterosexual celibacy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) defined as a hysterectomy, bilateral oophorectomy or bilateral tubal ligation; 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

• Prior malignancy is allowed providing it does not require concurrent therapy; exception: active hormonal therapy is allowed

• Patients must not be receiving valproic acid

• All patients must be informed of the investigational nature of this study; patients or a legally authorized representative must sign and give written informed consent in accordance with institutional and federal guidelines

• As 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

• STEP 2 - CONSOLIDATION

• Patients may be registered for consolidation provided that they were eligible for the initial induction/re-induction registration and satisfy the following additional criteria:

• Patients must have achieved morphologic remission (complete remission [CR] or complete remission with incomplete blood count recover [CRi]) after completion of induction or re-induction therapy; patient must remain in remission until beginning consolidation and this must be documented by bone marrow and peripheral blood examination within 28 days prior to registration to Step 2

• All non-hematologic treatment related toxicities that are deemed clinically significant by the treating physician must have resolved to =< grade 2

• Patients must not have received allogeneic stem cell transplant

Related Conditions & MeSH terms

• Acute Myeloid Leukemia
• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Untreated Adult Acute Myeloid Leukemia

Intervention

Procedure:
• Allogeneic Hematopoietic Stem Cell Transplantation
Undergo allogeneic transplant

Drug:
• Cytarabine
Given IV
• Daunorubicin Hydrochloride
Given IV
• Idarubicin
Given IV

Other:
• Laboratory Biomarker Analysis
Correlative studies

Drug:
• Vorinostat
Given PO

Locations

Country	Name	City	State
Canada	Tom Baker Cancer Centre	Calgary	Alberta
Canada	QEII Health Sciences Centre/Nova Scotia Health Authority	Halifax	Nova Scotia
Canada	The Moncton Hospital	Moncton	New Brunswick
Canada	CIUSSSEMTL-Hopital Maisonneuve-Rosemont	Montreal	Quebec
Canada	Allan Blair Cancer Centre	Regina	Saskatchewan
Canada	Atlantic Health Sciences Corporation-Saint John Regional Hospital	Saint John	New Brunswick
United States	Providence Regional Cancer System-Aberdeen	Aberdeen	Washington
United States	Summa Akron City Hospital/Cooper Cancer Center	Akron	Ohio
United States	University of New Mexico Cancer Center	Albuquerque	New Mexico
United States	American Fork Hospital / Huntsman Intermountain Cancer Center	American Fork	Utah
United States	McFarland Clinic PC-William R Bliss Cancer Center	Ames	Iowa
United States	Cancer Care Center at Island Hospital	Anacortes	Washington
United States	Alaska Breast Care and Surgery LLC	Anchorage	Alaska
United States	Alaska Oncology and Hematology LLC	Anchorage	Alaska
United States	Alaska Regional Hospital	Anchorage	Alaska
United States	Alaska Women's Cancer Care	Anchorage	Alaska
United States	Anchorage Oncology Centre	Anchorage	Alaska
United States	Anchorage Radiation Therapy Center	Anchorage	Alaska
United States	Katmai Oncology Group	Anchorage	Alaska
United States	Providence Alaska Medical Center	Anchorage	Alaska
United States	AnMed Health Cancer Center	Anderson	South Carolina
United States	Michigan Cancer Research Consortium NCORP	Ann Arbor	Michigan
United States	Saint Joseph Mercy Hospital	Ann Arbor	Michigan
United States	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan
United States	Asheville Hematology-Oncology Associates	Asheville	North Carolina
United States	Cancer Care of Western North Carolina	Asheville	North Carolina
United States	Hope Women's Cancer Centers-Asheville	Asheville	North Carolina
United States	Mission Hospital-Memorial Campus	Asheville	North Carolina
United States	Mountain Radiation Oncology	Asheville	North Carolina
United States	Northside Hospital	Atlanta	Georgia
United States	Harold Alfond Center for Cancer Care	Augusta	Maine
United States	Johns Hopkins University/Sidney Kimmel Cancer Center	Baltimore	Maryland
United States	Eastern Maine Medical Center	Bangor	Maine
United States	Summa Barberton Hospital	Barberton	Ohio
United States	Flaget Memorial Hospital	Bardstown	Kentucky
United States	Baton Rouge General Medical Center	Baton Rouge	Louisiana
United States	Hematology/Oncology Clinic LLP	Baton Rouge	Louisiana
United States	Bronson Battle Creek	Battle Creek	Michigan
United States	Swedish Cancer Institute-Eastside Oncology Hematology	Bellevue	Washington
United States	PeaceHealth Saint Joseph Medical Center	Bellingham	Washington
United States	Saint Charles Health System	Bend	Oregon
United States	Central Vermont Medical Center/National Life Cancer Treatment	Berlin	Vermont
United States	Spectrum Health Big Rapids Hospital	Big Rapids	Michigan
United States	Billings Clinic Cancer Center	Billings	Montana
United States	Montana Cancer Consortium NCORP	Billings	Montana
United States	Saint Vincent Frontier Cancer Center	Billings	Montana
United States	Saint Vincent Healthcare	Billings	Montana
United States	University of Alabama at Birmingham Cancer Center	Birmingham	Alabama
United States	Illinois CancerCare-Bloomington	Bloomington	Illinois
United States	Saint Joseph Medical Center	Bloomington	Illinois
United States	Saint Alphonsus Cancer Care Center-Boise	Boise	Idaho
United States	Saint Luke's Mountain States Tumor Institute	Boise	Idaho
United States	Central Care Cancer Center-Carrie J Babb Cancer Center	Bolivar	Missouri
United States	Parkland Health Center-Bonne Terre	Bonne Terre	Missouri
United States	McFarland Clinic PC-Boone	Boone	Iowa
United States	Brigham and Women's Hospital	Boston	Massachusetts
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Massachusetts General Hospital Cancer Center	Boston	Massachusetts
United States	Tufts Medical Center	Boston	Massachusetts
United States	Bozeman Deaconess Hospital	Bozeman	Montana
United States	CoxHealth Cancer Center	Branson	Missouri
United States	Harrison HealthPartners Hematology and Oncology-Bremerton	Bremerton	Washington
United States	Harrison Medical Center	Bremerton	Washington
United States	Transylvania Regional Hospital	Brevard	North Carolina
United States	Lafayette Family Cancer Center-EMMC	Brewer	Maine
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	Providence Saint Joseph Medical Center/Disney Family Cancer Center	Burbank	California
United States	Highline Medical Center-Main Campus	Burien	Washington
United States	University of Vermont College of Medicine	Burlington	Vermont
United States	Fairview Ridges Hospital	Burnsville	Minnesota
United States	Saint James Community Hospital and Cancer Treatment Center	Butte	Montana
United States	Illinois CancerCare-Canton	Canton	Illinois
United States	Saint Francis Medical Center	Cape Girardeau	Missouri
United States	Southeast Cancer Center	Cape Girardeau	Missouri
United States	Memorial Hospital of Carbondale	Carbondale	Illinois
United States	Illinois CancerCare-Carthage	Carthage	Illinois
United States	Rocky Mountain Oncology	Casper	Wyoming
United States	Sandra L Maxwell Cancer Center	Cedar City	Utah
United States	Miami Valley Hospital South	Centerville	Ohio
United States	Centralia Oncology Clinic	Centralia	Illinois
United States	Providence Regional Cancer System-Centralia	Centralia	Washington
United States	Cancer Center of Kansas - Chanute	Chanute	Kansas
United States	Medical University of South Carolina	Charleston	South Carolina
United States	Memorial Hospital	Chattanooga	Tennessee
United States	Mount Sinai Hospital Medical Center	Chicago	Illinois
United States	Northwestern University	Chicago	Illinois
United States	University of Chicago Comprehensive Cancer Center	Chicago	Illinois
United States	Bethesda North Hospital	Cincinnati	Ohio
United States	Good Samaritan Hospital - Cincinnati	Cincinnati	Ohio
United States	Oncology Hematology Care Inc - Anderson	Cincinnati	Ohio
United States	Oncology Hematology Care Inc-Blue Ash	Cincinnati	Ohio
United States	Oncology Hematology Care Inc-Eden Park	Cincinnati	Ohio
United States	Oncology Hematology Care Inc-Kenwood	Cincinnati	Ohio
United States	Oncology Hematology Care Inc-Mercy West	Cincinnati	Ohio
United States	The Jewish Hospital	Cincinnati	Ohio
United States	TriHealth Cancer Institute-Anderson	Cincinnati	Ohio
United States	TriHealth Cancer Institute-Westside	Cincinnati	Ohio
United States	Clackamas Radiation Oncology Center	Clackamas	Oregon
United States	Providence Oncology and Hematology Care Southeast	Clackamas	Oregon
United States	Case Western Reserve University	Cleveland	Ohio
United States	Cleveland Clinic Foundation	Cleveland	Ohio
United States	MetroHealth Medical Center	Cleveland	Ohio
United States	Medical Oncology and Hematology Associates-West Des Moines	Clive	Iowa
United States	Mercy Cancer Center-West Lakes	Clive	Iowa
United States	Big Horn Basin Cancer Center	Cody	Wyoming
United States	Billings Clinic-Cody	Cody	Wyoming
United States	Kootenai Medical Center	Coeur d'Alene	Idaho
United States	University of Missouri - Ellis Fischel	Columbia	Missouri
United States	Mercy Hospital	Coon Rapids	Minnesota
United States	Bay Area Hospital	Coos Bay	Oregon
United States	Commonwealth Cancer Center-Corbin	Corbin	Kentucky
United States	Alegent Health Mercy Hospital	Council Bluffs	Iowa
United States	Oncology Hematology Care Inc-Crestview	Crestview Hills	Kentucky
United States	Siteman Cancer Center at West County Hospital	Creve Coeur	Missouri
United States	Northside Hospital-Forsyth	Cumming	Georgia
United States	Geisinger Medical Center	Danville	Pennsylvania
United States	Dayton NCI Community Oncology Research Program	Dayton	Ohio
United States	Good Samaritan Hospital - Dayton	Dayton	Ohio
United States	Grandview Hospital	Dayton	Ohio
United States	Miami Valley Hospital	Dayton	Ohio
United States	Samaritan North Health Center	Dayton	Ohio
United States	Beaumont Hospital-Dearborn	Dearborn	Michigan
United States	Cancer Care Center of Decatur	Decatur	Illinois
United States	Decatur Memorial Hospital	Decatur	Illinois
United States	Medical Oncology and Hematology Associates-Laurel	Des Moines	Iowa
United States	Mercy Medical Center - Des Moines	Des Moines	Iowa
United States	Saint John Hospital and Medical Center	Detroit	Michigan
United States	Wayne State University/Karmanos Cancer Institute	Detroit	Michigan
United States	Cancer Center of Kansas - Dodge City	Dodge City	Kansas
United States	City of Hope Comprehensive Cancer Center	Duarte	California
United States	Duke University Medical Center	Durham	North Carolina
United States	Marshfield Clinic Cancer Center at Sacred Heart	Eau Claire	Wisconsin
United States	Sacred Heart Hospital	Eau Claire	Wisconsin
United States	Fairview-Southdale Hospital	Edina	Minnesota
United States	Swedish Medical Center-Edmonds	Edmonds	Washington
United States	Crossroads Cancer Center	Effingham	Illinois
United States	Cancer Center of Kansas - El Dorado	El Dorado	Kansas
United States	Saint Elizabeth Hospital	Enumclaw	Washington
United States	Ephrata Cancer Center	Ephrata	Pennsylvania
United States	Ephrata Community Hospital	Ephrata	Pennsylvania
United States	Green Bay Oncology - Escanaba	Escanaba	Michigan
United States	Illinois CancerCare-Eureka	Eureka	Illinois
United States	NorthShore University HealthSystem-Evanston Hospital	Evanston	Illinois
United States	Providence Regional Cancer Partnership	Everett	Washington
United States	Oncology Hematology Care Inc-Healthplex	Fairfield	Ohio
United States	Weisberg Cancer Treatment Center	Farmington Hills	Michigan
United States	Saint Francis Hospital	Federal Way	Washington
United States	Blanchard Valley Hospital	Findlay	Ohio
United States	Genesys Hurley Cancer Institute	Flint	Michigan
United States	Hurley Medical Center	Flint	Michigan
United States	Poudre Valley Hospital	Fort Collins	Colorado
United States	Cancer Center of Kansas - Fort Scott	Fort Scott	Kansas
United States	Fort Wayne Medical Oncology and Hematology Inc-Parkview	Fort Wayne	Indiana
United States	Angel Medical Center	Franklin	North Carolina
United States	Atrium Medical Center-Middletown Regional Hospital	Franklin	Ohio
United States	Vanderbilt-Ingram Cancer Center Cool Springs	Franklin	Tennessee
United States	Unity Hospital	Fridley	Minnesota
United States	Saint Luke's Mountain States Tumor Institute - Fruitland	Fruitland	Idaho
United States	University of Florida Health Science Center - Gainesville	Gainesville	Florida
United States	Illinois CancerCare-Galesburg	Galesburg	Illinois
United States	Western Illinois Cancer Treatment Center	Galesburg	Illinois
United States	Adams Cancer Center	Gettysburg	Pennsylvania
United States	NorthShore University HealthSystem-Glenbrook Hospital	Glenview	Illinois
United States	CHI Health Saint Francis	Grand Island	Nebraska
United States	Cancer Research Consortium of West Michigan NCORP	Grand Rapids	Michigan
United States	Mercy Health Saint Mary's	Grand Rapids	Michigan
United States	Spectrum Health at Butterworth Campus	Grand Rapids	Michigan
United States	Benefis Healthcare- Sletten Cancer Institute	Great Falls	Montana
United States	Great Falls Clinic	Great Falls	Montana
United States	Green Bay Oncology at Saint Vincent Hospital	Green Bay	Wisconsin
United States	Green Bay Oncology Limited at Saint Mary's Hospital	Green Bay	Wisconsin
United States	Saint Vincent Hospital Cancer Center at Saint Mary's	Green Bay	Wisconsin
United States	Saint Vincent Hospital Cancer Center Green Bay	Green Bay	Wisconsin
United States	Saint Francis Hospital	Greenville	South Carolina
United States	Wayne Hospital	Greenville	Ohio
United States	Gibbs Cancer Center-Pelham	Greer	South Carolina
United States	Cherry Tree Cancer Center	Hanover	Pennsylvania
United States	Hartford Hospital	Hartford	Connecticut
United States	Smilow Cancer Hospital Care Center at Saint Francis	Hartford	Connecticut
United States	Saint Peter's Community Hospital	Helena	Montana
United States	Park Ridge Hospital Breast Health Center	Hendersonville	North Carolina
United States	Penn State Milton S Hershey Medical Center	Hershey	Pennsylvania
United States	Hematology Oncology Associates of Illinois-Highland Park	Highland Park	Illinois
United States	NorthShore University HealthSystem-Highland Park Hospital	Highland Park	Illinois
United States	Pulmonary Medicine Center of Chattanooga-Hixson	Hixson	Tennessee
United States	Mercy Cancer Center-Hot Springs	Hot Springs	Arkansas
United States	Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center	Houston	Texas
United States	Ben Taub General Hospital	Houston	Texas
United States	M D Anderson Cancer Center	Houston	Texas
United States	Michael E DeBakey VA Medical Center	Houston	Texas
United States	Hutchinson Area Health Care	Hutchinson	Minnesota
United States	Cancer Center of Kansas-Independence	Independence	Kansas
United States	Centerpoint Medical Center LLC	Independence	Missouri
United States	Franciscan Health Indianapolis	Indianapolis	Indiana
United States	Indiana University/Melvin and Bren Simon Cancer Center	Indianapolis	Indiana
United States	IU Health Central Indiana Cancer Centers-East	Indianapolis	Indiana
United States	University of Iowa/Holden Comprehensive Cancer Center	Iowa City	Iowa
United States	Green Bay Oncology - Iron Mountain	Iron Mountain	Michigan
United States	Swedish Cancer Institute-Issaquah	Issaquah	Washington
United States	Allegiance Health	Jackson	Michigan
United States	University of Mississippi Medical Center	Jackson	Mississippi
United States	McFarland Clinic PC-Jefferson	Jefferson	Iowa
United States	Capital Region Medical Center-Goldschmidt Cancer Center	Jefferson City	Missouri
United States	UW Cancer Center Johnson Creek	Johnson Creek	Wisconsin
United States	Freeman Health System	Joplin	Missouri
United States	Mercy Hospital-Joplin	Joplin	Missouri
United States	Borgess Medical Center	Kalamazoo	Michigan
United States	Bronson Methodist Hospital	Kalamazoo	Michigan
United States	West Michigan Cancer Center	Kalamazoo	Michigan
United States	Kalispell Regional Medical Center	Kalispell	Montana
United States	Presence Saint Mary's Hospital	Kankakee	Illinois
United States	Heartland Hematology and Oncology Associates Incorporated	Kansas City	Missouri
United States	Research Medical Center	Kansas City	Missouri
United States	Saint Luke's Hospital of Kansas City	Kansas City	Missouri
United States	University of Kansas Cancer Center	Kansas City	Kansas
United States	CHI Health Good Samaritan	Kearney	Nebraska
United States	Heartland Hematology and Oncology	Kearney	Nebraska
United States	Kadlec Clinic Hematology and Oncology	Kennewick	Washington
United States	Kettering Medical Center	Kettering	Ohio
United States	Illinois CancerCare-Kewanee Clinic	Kewanee	Illinois
United States	Cancer Center of Kansas-Kingman	Kingman	Kansas
United States	Kinston Medical Specialists PA	Kinston	North Carolina
United States	Seattle Cancer Care Alliance at EvergreenHealth	Kirkland	Washington
United States	Gundersen Lutheran Medical Center	La Crosse	Wisconsin
United States	UC San Diego Moores Cancer Center	La Jolla	California
United States	Providence Regional Cancer System-Lacey	Lacey	Washington
United States	Saint Clare Hospital	Lakewood	Washington
United States	Carolina Blood and Cancer Care Associates PA-Lancaster	Lancaster	South Carolina
United States	Sparrow Hospital	Lansing	Michigan
United States	Lawrence Memorial Hospital	Lawrence	Kansas
United States	Dartmouth Hitchcock Medical Center	Lebanon	New Hampshire
United States	Saint Luke's East - Lee's Summit	Lee's Summit	Missouri
United States	Lewistown Hospital	Lewistown	Pennsylvania
United States	Saint Joseph Hospital East	Lexington	Kentucky
United States	Saint Joseph Radiation Oncology Resource Center	Lexington	Kentucky
United States	University of Kentucky/Markey Cancer Center	Lexington	Kentucky
United States	Cancer Center of Kansas-Liberal	Liberal	Kansas
United States	Liberty Radiation Oncology Center	Liberty	Missouri
United States	NorthShore Hematology Oncology-Libertyville	Libertyville	Illinois
United States	Saint Elizabeth Regional Medical Center	Lincoln	Nebraska
United States	Saint Mary Mercy Hospital	Livonia	Michigan
United States	Logan Regional Hospital	Logan	Utah
United States	PeaceHealth Saint John Medical Center	Longview	Washington
United States	Jewish Hospital	Louisville	Kentucky
United States	Jewish Hospital Medical Center Northeast	Louisville	Kentucky
United States	Saints Mary and Elizabeth Hospital	Louisville	Kentucky
United States	Illinois CancerCare-Macomb	Macomb	Illinois
United States	University of Wisconsin Hospital and Clinics	Madison	Wisconsin
United States	North Shore University Hospital	Manhasset	New York
United States	Cancer Center of Kansas-Manhattan	Manhattan	Kansas
United States	Holy Family Memorial Hospital	Manitowoc	Wisconsin
United States	Minnesota Oncology Hematology PA-Maplewood	Maplewood	Minnesota
United States	Saint John's Hospital - Healtheast	Maplewood	Minnesota
United States	Bay Area Medical Center	Marinette	Wisconsin
United States	McDowell Hospital	Marion	North Carolina
United States	West Jefferson Medical Center	Marrero	Louisiana
United States	McFarland Clinic PC-Marshalltown	Marshalltown	Iowa
United States	Marshfield Clinic	Marshfield	Wisconsin
United States	Marshfield Medical Center	Marshfield	Wisconsin
United States	Fremont - Rideout Cancer Center	Marysville	California
United States	Loyola University Medical Center	Maywood	Illinois
United States	Cancer Center of Kansas - McPherson	McPherson	Kansas
United States	Saint Luke's Mountain States Tumor Institute - Meridian	Meridian	Idaho
United States	Froedtert and the Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Providence Milwaukie Hospital	Milwaukie	Oregon
United States	Abbott-Northwestern Hospital	Minneapolis	Minnesota
United States	Health Partners Inc	Minneapolis	Minnesota
United States	Hennepin County Medical Center	Minneapolis	Minnesota
United States	Marshfield Clinic-Minocqua Center	Minocqua	Wisconsin
United States	Community Medical Hospital	Missoula	Montana
United States	Montana Cancer Specialists	Missoula	Montana
United States	Saint Patrick Hospital - Community Hospital	Missoula	Montana
United States	Good Samaritan Regional Health Center	Mount Vernon	Illinois
United States	Skagit Valley Hospital	Mount Vernon	Washington
United States	ProHealth D N Greenwald Center	Mukwonago	Wisconsin
United States	Intermountain Medical Center	Murray	Utah
United States	Mercy Health Mercy Campus	Muskegon	Michigan
United States	Saint Luke's Mountain States Tumor Institute - Nampa	Nampa	Idaho
United States	Vanderbilt Breast Center at One Hundred Oaks	Nashville	Tennessee
United States	Vanderbilt University/Ingram Cancer Center	Nashville	Tennessee
United States	Yale University	New Haven	Connecticut
United States	Long Island Jewish Medical Center	New Hyde Park	New York
United States	Northwell Health/Center for Advanced Medicine	New Hyde Park	New York
United States	Tulane University Health Sciences Center	New Orleans	Louisiana
United States	Cancer Center of Western Wisconsin	New Richmond	Wisconsin
United States	New Ulm Medical Center	New Ulm	Minnesota
United States	Mount Sinai Hospital	New York	New York
United States	Providence Newberg Medical Center	Newberg	Oregon
United States	Cancer Center of Kansas - Newton	Newton	Kansas
United States	Illinois Cancer Specialists-Niles	Niles	Illinois
United States	Assarian Cancer Center	Novi	Michigan
United States	ProHealth Oconomowoc Memorial Hospital	Oconomowoc	Wisconsin
United States	Green Bay Oncology - Oconto Falls	Oconto Falls	Wisconsin
United States	McKay-Dee Hospital Center	Ogden	Utah
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	Alegent Health Bergan Mercy Medical Center	Omaha	Nebraska
United States	Alegent Health Immanuel Medical Center	Omaha	Nebraska
United States	Alegent Health Lakeside Hospital	Omaha	Nebraska
United States	Creighton University Medical Center	Omaha	Nebraska
United States	Hemotology and Oncology Consultants PC	Omaha	Nebraska
United States	University of Nebraska Medical Center	Omaha	Nebraska
United States	Memorial GYN Plus	Ooltewah	Tennessee
United States	UC Irvine Health/Chao Family Comprehensive Cancer Center	Orange	California
United States	Providence Willamette Falls Medical Center	Oregon City	Oregon
United States	Illinois CancerCare-Ottawa Clinic	Ottawa	Illinois
United States	Radiation Oncology of Northern Illinois	Ottawa	Illinois
United States	Menorah Medical Center	Overland Park	Kansas
United States	Saint Luke's South Hospital	Overland Park	Kansas
United States	Stanford Cancer Institute Palo Alto	Palo Alto	California
United States	Midlands Community Hospital	Papillion	Nebraska
United States	Cancer Center of Kansas - Parsons	Parsons	Kansas
United States	Saint Joseph's Regional Medical Center	Paterson	New Jersey
United States	Illinois CancerCare-Pekin	Pekin	Illinois
United States	OSF Saint Francis Radiation Oncology at Pekin Cancer Treatment Center	Pekin	Illinois
United States	Illinois CancerCare-Peoria	Peoria	Illinois
United States	Methodist Medical Center of Illinois	Peoria	Illinois
United States	OSF Saint Francis Medical Center	Peoria	Illinois
United States	OSF Saint Francis Radiation Oncology at Peoria Cancer Center	Peoria	Illinois
United States	Illinois CancerCare-Peru	Peru	Illinois
United States	Valley Radiation Oncology	Peru	Illinois
United States	Drexel University School of Medicine	Philadelphia	Pennsylvania
United States	University of Pennsylvania/Abramson Cancer Center	Philadelphia	Pennsylvania
United States	Saint Joseph Mercy Oakland	Pontiac	Michigan
United States	Lake Huron Medical Center	Port Huron	Michigan
United States	Oregon Health and Science University	Portland	Oregon
United States	Providence Portland Medical Center	Portland	Oregon
United States	Providence Saint Vincent Medical Center	Portland	Oregon
United States	Kootenai Cancer Center	Post Falls	Idaho
United States	Harrison HealthPartners Hematology and Oncology-Poulsbo	Poulsbo	Washington
United States	Kansas City NCI Community Oncology Research Program	Prairie Village	Kansas
United States	Cancer Center of Kansas - Pratt	Pratt	Kansas
United States	Illinois CancerCare-Princeton	Princeton	Illinois
United States	Utah Valley Regional Medical Center	Provo	Utah
United States	Spectrum Health Reed City Hospital	Reed City	Michigan
United States	Marshfield Clinic at James Beck Cancer Center	Rhinelander	Wisconsin
United States	Marshfield Clinic-Rice Lake Center	Rice Lake	Wisconsin
United States	Reid Health	Richmond	Indiana
United States	Virginia Commonwealth University/Massey Cancer Center	Richmond	Virginia
United States	North Memorial Medical Health Center	Robbinsdale	Minnesota
United States	Mayo Clinic	Rochester	Minnesota
United States	University of Rochester	Rochester	New York
United States	Carolina Blood and Cancer Care Associates PA	Rock Hill	South Carolina
United States	SwedishAmerican Regional Cancer Center/ACT	Rockford	Illinois
United States	Delbert Day Cancer Institute at PCRMC	Rolla	Missouri
United States	Saint John's Clinic-Rolla-Cancer and Hematology	Rolla	Missouri
United States	University of California Davis Comprehensive Cancer Center	Sacramento	California
United States	Saint Mary's of Michigan	Saginaw	Michigan
United States	Dixie Medical Center Regional Cancer Center	Saint George	Utah
United States	Heartland Regional Medical Center	Saint Joseph	Missouri
United States	Mercy Hospital Saint Louis	Saint Louis	Missouri
United States	Missouri Baptist Medical Center	Saint Louis	Missouri
United States	Saint Louis Cancer and Breast Institute-South City	Saint Louis	Missouri
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Metro Minnesota Community Oncology Research Consortium	Saint Louis Park	Minnesota
United States	Park Nicollet Clinic - Saint Louis Park	Saint Louis Park	Minnesota
United States	Regions Hospital	Saint Paul	Minnesota
United States	United Hospital	Saint Paul	Minnesota
United States	Sainte Genevieve County Memorial Hospital	Sainte Genevieve	Missouri
United States	Cancer Center of Kansas - Salina	Salina	Kansas
United States	LDS Hospital	Salt Lake City	Utah
United States	Utah Cancer Specialists-Salt Lake City	Salt Lake City	Utah
United States	Kootenai Cancer Clinic	Sandpoint	Idaho
United States	Fred Hutchinson Cancer Research Center	Seattle	Washington
United States	Harborview Medical Center	Seattle	Washington
United States	Kaiser Permanente Washington	Seattle	Washington
United States	Minor and James Medical PLLC	Seattle	Washington
United States	Pacific Gynecology Specialists	Seattle	Washington
United States	Swedish Medical Center-Ballard Campus	Seattle	Washington
United States	Swedish Medical Center-First Hill	Seattle	Washington
United States	University of Washington Medical Center	Seattle	Washington
United States	United General Hospital	Sedro-Woolley	Washington
United States	Saint Francis Regional Medical Center	Shakopee	Minnesota
United States	HSHS Saint Nicholas Hospital	Sheboygan	Wisconsin
United States	Providence Regional Cancer System-Shelton	Shelton	Washington
United States	Jewish Hospital Medical Center South	Shepherdsville	Kentucky
United States	Welch Cancer Center	Sheridan	Wyoming
United States	Mercy Medical Center-Sioux City	Sioux City	Iowa
United States	Saint Luke's Regional Medical Center	Sioux City	Iowa
United States	Siouxland Regional Cancer Center	Sioux City	Iowa
United States	Hematology Oncology Associates of Illinois - Skokie	Skokie	Illinois
United States	North Shore Medical Center	Skokie	Illinois
United States	Providence Hospital-Southfield Cancer Center	Southfield	Michigan
United States	Spartanburg Medical Center	Spartanburg	South Carolina
United States	Cancer Care Northwest - Spokane South	Spokane	Washington
United States	Evergreen Hematology and Oncology PS	Spokane	Washington
United States	Rockwood Cancer Treatment Center-DHEC-Downtown	Spokane	Washington
United States	Rockwood Clinic	Spokane	Washington
United States	Rockwood Clinic Cancer Treatment Center-Valley	Spokane Valley	Washington
United States	Central Illinois Hematology Oncology Center	Springfield	Illinois
United States	CoxHealth South Hospital	Springfield	Missouri
United States	Memorial Medical Center	Springfield	Illinois
United States	Mercy Hospital Springfield	Springfield	Missouri
United States	Southern Illinois University School of Medicine	Springfield	Illinois
United States	Springfield Clinic	Springfield	Illinois
United States	Springfield Regional Cancer Center	Springfield	Ohio
United States	Springfield Regional Medical Center	Springfield	Ohio
United States	Blue Ridge Regional Hospital	Spruce Pine	North Carolina
United States	Marshfield Clinic Cancer Care at Saint Michael's Hospital	Stevens Point	Wisconsin
United States	Lakeview Hospital	Stillwater	Minnesota
United States	Green Bay Oncology - Sturgeon Bay	Sturgeon Bay	Wisconsin
United States	Missouri Baptist Sullivan Hospital	Sullivan	Missouri
United States	Missouri Baptist Outpatient Center-Sunset Hills	Sunset Hills	Missouri
United States	Cancer Care Specialists of Illinois-Swansea	Swansea	Illinois
United States	Franciscan Research Center-Northwest Medical Plaza	Tacoma	Washington
United States	Northwest Medical Specialties PLLC	Tacoma	Washington
United States	Moffitt Cancer Center	Tampa	Florida
United States	Munson Medical Center	Traverse City	Michigan
United States	Upper Valley Medical Center	Troy	Ohio
United States	The University of Arizona Medical Center-University Campus	Tucson	Arizona
United States	University of Arizona Cancer Center-North Campus	Tucson	Arizona
United States	University of Arizona Cancer Center-Orange Grove Campus	Tucson	Arizona
United States	Natalie Warren Bryant Cancer Center at Saint Francis	Tulsa	Oklahoma
United States	Warren Clinic Oncology-Tulsa	Tulsa	Oklahoma
United States	Saint Luke's Mountain States Tumor Institute-Twin Falls	Twin Falls	Idaho
United States	MGC Hematology Oncology-Union	Union	South Carolina
United States	Compass Oncology Vancouver	Vancouver	Washington
United States	PeaceHealth Southwest Medical Center	Vancouver	Washington
United States	Ridgeview Medical Center	Waconia	Minnesota
United States	Providence Saint Mary Regional Cancer Center	Walla Walla	Washington
United States	Saint John Macomb-Oakland Hospital	Warren	Michigan
United States	ProHealth Waukesha Memorial Hospital	Waukesha	Wisconsin
United States	UW Cancer Center at ProHealth Care	Waukesha	Wisconsin
United States	Marshfield Clinic-Wausau Center	Wausau	Wisconsin
United States	Cancer Center of Kansas - Wellington	Wellington	Kansas
United States	Wenatchee Valley Hospital and Clinics	Wenatchee	Washington
United States	Mercy Medical Center-West Lakes	West Des Moines	Iowa
United States	Marshfield Clinic - Weston Center	Weston	Wisconsin
United States	Saint Clare's Hospital	Weston	Wisconsin
United States	Associates In Womens Health	Wichita	Kansas
United States	Cancer Center of Kansas - Wichita	Wichita	Kansas
United States	Cancer Center of Kansas-Wichita Medical Arts Tower	Wichita	Kansas
United States	Via Christi Regional Medical Center	Wichita	Kansas
United States	Wesley Medical Center	Wichita	Kansas
United States	Wichita NCI Community Oncology Research Program	Wichita	Kansas
United States	Rice Memorial Hospital	Willmar	Minnesota
United States	Cancer Center of Kansas - Winfield	Winfield	Kansas
United States	Southeast Clinical Oncology Research (SCOR) Consortium NCORP	Winston-Salem	North Carolina
United States	Wake Forest University Health Sciences	Winston-Salem	North Carolina
United States	Marshfield Clinic - Wisconsin Rapids Center	Wisconsin Rapids	Wisconsin
United States	Minnesota Oncology Hematology PA-Woodbury	Woodbury	Minnesota
United States	Wright-Patterson Medical Center	Wright-Patterson Air Force Base	Ohio
United States	Greene Memorial Hospital	Xenia	Ohio
United States	North Star Lodge Cancer Center at Yakima Valley Memorial Hospital	Yakima	Washington
United States	Providence Regional Cancer System-Yelm	Yelm	Washington
United States	WellSpan Health-York Cancer Center	York	Pennsylvania
United States	WellSpan Health-York Hospital	York	Pennsylvania
United States	Yuma Cancer Center	Yuma	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Prevalence of the Mutation NPM1 in Patients on This Study.	To estimate the prevalence of the mutation NPM1 in this patient population.	Baseline
Other	Prevalence of the Mutations IDH1, IDH2, TET2, DMT3A in Patients on This Study	To estimate the prevalence of these mutations in this patient population.; This objective will be analyzed as funding allows.	Baseline
Other	Cytogenetic Risk Distribution of Patients on This Study	To estimate the cytogenetic risk distribution of patients on this study.	Baseline
Other	Overall Survival (OS)	To compare OS between patients who receive standard 7+3 therapy or IA to patients who receive IA + vorinostat.; OS is calculated for all patients from date of registration to date of death due to any cause. Patients last known to be alive are censored at date of last contact.; 2-year OS by arm will be estimated using the Kaplan-Meier method.	OS assessed for up to 5 years, 2 year OS reported
Other	Complete Response (CR) Rate	To compare the complete response rate between patients who receive standard 7+3 therapy or IA to patients who receive IA + vorinostat.; Complete response is defined as: ANC >= 1,000/mcl, platelet count >= 100,000/mcl, < 5% bone marrow blasts, no Auer rods, no evidence of extramedullary disease (no requirements for marrow cellularity or hemoglobin concentration)	Up to 5 years
Other	Disease-free Survival (DFS)	To compare the disease-free survival (DFS) between patients who receive standard 7+3 therapy or IA to patients who receive IA + vorinostat.; DFS is calculated for patients who have achieved a CR or CRi (complete response with incomplete blood count recovery) . DFS will be measured from the date of CR or CRi until relapse from CR or CRi for death from any cause. Observation is censored at the date of last follow-up for patients last known to be alive without report of relapse.; 2-year DFS by arm will be estimated using the Kaplan-Meier method.	DFS assessed for up to 5 years, 2 year DFS reported
Primary	Event-free Survival (EFS)	EFS is calculated for all patients from the date of initial registration on study until the first of the following: death from any cause, relapse from remission (CR or CRi) or completion of protocol Induction/Re-Induction therapy without documentation of CR or CRi.; 2-year EFS by arm will be estimated using the Kaplan-Meier method. EFS will be compared between Arm I and Arm III and between Arm II and Arm III using Cox proportional hazards regression.	EFS assessed for up to 5 years, 2 year EFS reported
Primary	Rate of Allogeneic HCT	The goal of the transplant objective is to determine whether it is possible to conduct allogeneic HCT on 60% or more of adults with high-risk AML in first complete remission (alternative). If 40% or fewer of high-risk patients in CR can be transplanted, the proposed transplant support system will not be considered feasible. A one-sided binomial test compared to the null transplant rate will be conducted.	Up to 5 years
Secondary	Disease-free Survival (DFS) Among High Risk Patients	DFS is calculated for patients who have achieved a CR or CRi (complete response with incomplete blood count recovery). DFS will be measured from the date of CR or CRi until relapse from CR or CRi for death from any cause. Observation is censored at the date of last follow-up for patients last known to be alive without report of relapse.; 2-year DFS for high risk patients will be estimated using the Kaplan-Meier method.	DFS assessed for up to 5 years, 2 year DFS reported
Secondary	EFS of Arm I Compared to Arm II	EFS is calculated for all patients from the date of initial registration on study until the first of the following: death from any cause, relapse from remission (CR or CRi) or completion of protocol Induction/Re-Induction therapy without documentation of CR or CRi.; A two-sided test of the hazard ratio (HR) of 7:3: IA (versus the null hypothesis of HR =1) will be done using a proportional hazards regression model with the stratification factors included as covariates.; 2-year EFS by arm will be estimated using the Kaplan-Meier method.	EFS assessed for up to 5 years, 2 year EFS reported
Secondary	Frequency and Severity of Toxicities	Number of patients with Grade 3-5 adverse events that were possibly, probably or definitely related to study drug are reported by given type of adverse event.	Up to 5 years