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A Randomized Phase II Trial of Azacitidine With or Without the Histone Deacetylase Inhibitor Entinostat for the Treatment of Myelodysplastic Syndrome, Chronic Myelomonocytic Leukemia (Dysplastic Type), and Acute Myeloid Leukemia With Multilineage Dysplasia


Phase 2
18 Years
N/A
Open (Enrolling)
Both
Chronic Myelomonocytic Leukemia, de Novo Myelodysplastic Syndromes, Previously Treated Myelodysplastic Syndromes, Untreated Adult Acute Myeloid Leukemia

Thank you

Trial Information

A Randomized Phase II Trial of Azacitidine With or Without the Histone Deacetylase Inhibitor Entinostat for the Treatment of Myelodysplastic Syndrome, Chronic Myelomonocytic Leukemia (Dysplastic Type), and Acute Myeloid Leukemia With Multilineage Dysplasia


PRIMARY OBJECTIVES:

I. Compare the overall response rate (complete, partial, and hematologic improvement-major
by International Working Group [IWG] criteria) in patients with treatment-induced or
non-treatment-induced myelodysplastic syndromes (MDS), chronic myelomonocytic leukemia
(dysplastic), or acute myeloid leukemia with multilineage dysplasia treated with azacitidine
with vs without entinostat.

II. Compare the major response rate (complete and partial responses by IWG criteria) in
patients treated with these regimens.

SECONDARY OBJECTIVES:

I. Evaluate the toxicity of azacitidine and entinostatin these patients. II. Identify
changes in gene promoter methylation and gene expression that may be associated with
response to azacitidine and entinostat.

III. Identify other molecular mechanisms (such as DNA damage) that may be associated with
response to azacitidine and entinostat.

OUTLINE: This is a randomized, multicenter study. Patients are first stratified according to
treatment-related disease (yes vs no), followed by a second stratification according to
disease (myelodysplastic syndromes [MDS] high/intermediate-2 vs MDS low/intermediate-1 vs
chronic myelomonocytic leukemia vs acute myeloid leukemia with multilineage dysplasia).
Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive azacitidine subcutaneously once daily on days 1-10.

ARM II: Patients receive azacitidine as in arm I and oral entinostat on days 3 and 10.

Treatment in both arms repeats every 28 days for at least 6 and up to 24 courses in the
absence of disease progression or unacceptable toxicity. After completion of study
treatment, patients are followed periodically for 5 years.


Inclusion Criteria:



- Bone marrow aspirate and/or biopsy-confirmed diagnosis of 1 of the following:

- Myelodysplastic syndromes (MDS)

- Any International Prognostic Score (IPSS) eligible

- Patients with low or intermediate-1 IPSS must have platelet count <
50,000/mm³ and/or absolute neutrophil count < 500/mm³

- Blast count < 20%

- Chronic myelomonocytic leukemia (dysplastic subtype)

- WBC < 12,000/mm³ (measured twice within the past 4 weeks, 2 weeks apart)

- Acute myeloid leukemia with multilineage dysplasia (AML-TLD)

- Formerly diagnosed refractory anemia with excess blasts in transformation
by FAB criteria allowed

- AML-TLD by WHO criteria allowed in patients with no history of antecedent
hematologic disorder

- WBC ≤ 30,000/mm³ (measured twice within the past 4 weeks, 2 weeks apart)

- WBC that has doubled over 4 weeks AND > 20,000/mm³ is not eligible

- Evidence of ≥ 20% blasts on review of the bone marrow aspirate and/or
biopsy

- SWOG patients must be enrolled in research study trial SWOG-9007

- Therapy-induced MDS, AML-TLD, or chronic myelomonocytic leukemia (dysplastic subtype)
allowed

- No clinical evidence of CNS or pulmonary leukostasis or disseminated intravascular
coagulation

- No clinical evidence of CNS leukemia

- No filgrastim (G-CSF) or pegfilgrastim during days 1-10 of each treatment course

- ECOG performance status 0-2

- Life expectancy ≥ 6 months

- Creatinine < 2.0 mg/dL

- Bilirubin normal (unless due to intramedullary or extramedullary hemolysis, or
Gilbert's syndrome)

- AST and ALT ≤ 2.5 times upper limit of normal

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- No active infections

- No advanced malignant hepatic tumors

- No other serious or uncontrolled medical conditions

- No known hypersensitivity to azacitidine or mannitol

- Recovered from prior therapy

- No prior azacitidine, decitabine or entinostat

- No prior induction chemotherapy for AML or stem cell transplantation

- No hematopoietic growth factors within 3 weeks prior to study entry

- No other concurrent investigational or commercial agents or therapies for the
malignancy

- No concurrent valproic acid, epoetin alfa, or darbepoetin alfa

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

The complete response rate, partial response rate, and trilineage response rate

Outcome Description:

Graded according to standard international response criteria.

Outcome Time Frame:

Up to 5 years

Safety Issue:

No

Principal Investigator

Steven Gore

Investigator Role:

Principal Investigator

Investigator Affiliation:

Eastern Cooperative Oncology Group

Authority:

United States: Food and Drug Administration

Study ID:

NCI-2009-01077

NCT ID:

NCT00313586

Start Date:

August 2006

Completion Date:

Related Keywords:

  • Chronic Myelomonocytic Leukemia
  • de Novo Myelodysplastic Syndromes
  • Previously Treated Myelodysplastic Syndromes
  • Untreated Adult Acute Myeloid Leukemia
  • Leukemia
  • Leukemia, Myeloid, Acute
  • Leukemia, Myeloid
  • Leukemia, Myelomonocytic, Chronic
  • Myelodysplastic Syndromes
  • Preleukemia
  • Leukemia, Myelomonocytic, Acute

Name

Location

Johns Hopkins UniversityBaltimore, Maryland  21205
Roswell Park Cancer InstituteBuffalo, New York  14263
Mayo ClinicRochester, Minnesota  55905
University of Iowa Hospitals and ClinicsIowa City, Iowa  52242
Fox Chase Cancer CenterPhiladelphia, Pennsylvania  19111
Boulder Community HospitalBoulder, Colorado  80301-9019
Porter Adventist HospitalDenver, Colorado  80210
Rose Medical CenterDenver, Colorado  80220
Swedish Medical CenterEnglewood, Colorado  80110
Sky Ridge Medical CenterLone Tree, Colorado  80124
North Suburban Medical CenterThornton, Colorado  80229
Geisinger Medical CenterDanville, Pennsylvania  17822-0001
Loyola University Medical CenterMaywood, Illinois  60153
Henry Ford HospitalDetroit, Michigan  48202
Methodist Medical Center of IllinoisPeoria, Illinois  61636
Akron General Medical CenterAkron, Ohio  44302
York HospitalYork, Pennsylvania  17315
Jackson-Madison County General HospitalJackson, Tennessee  38301
North Shore University HospitalManhasset, New York  11030
Boston Medical CenterBoston, Massachusetts  02118
Eastern Maine Medical CenterBangor, Maine  04401
Via Christi Regional Medical CenterWichita, Kansas  67214
Carolinas Medical CenterCharlotte, North Carolina  28232-2861
Scott and White Memorial HospitalTemple, Texas  76508
Iowa Methodist Medical CenterDes Moines, Iowa  50309
Iowa Lutheran HospitalDes Moines, Iowa  50316-2301
University of Wisconsin Hospital and ClinicsMadison, Wisconsin  53792-0001
Great Falls ClinicGreat Falls, Montana  59405
Long Island Jewish Medical CenterNew Hyde Park, New York  11040
Mount Sinai Medical CenterNew York, New York  10029
Montefiore Medical CenterBronx, New York  10467-2490
Sibley Memorial HospitalWashington, District of Columbia  20016
North Colorado Medical CenterGreeley, Colorado  80631
McKee Medical CenterLoveland, Colorado  80539
Cancer Center of Kansas - ChanuteChanute, Kansas  66720
Cancer Center of Kansas - Dodge CityDodge City, Kansas  67801
Cancer Center of Kansas - NewtonNewton, Kansas  67114
Cancer Center of Kansas - SalinaSalina, Kansas  67042
Cancer Center of Kansas - WellingtonWellington, Kansas  67152
Associates in Womens HealthWichita, Kansas  67203
Cancer Center of Kansas - WinfieldWinfield, Kansas  67156
Northern Rockies Radiation Oncology CenterBillings, Montana  59101
Bozeman Deaconess HospitalBozeman, Montana  59715
Big Sky OncologyGreat Falls, Montana  59405
Kalispell Medical OncologyKalispell, Montana  59901
Kalispell Regional Medical CenterKalispell, Montana  59901
Medical X-Ray CenterSioux Falls, South Dakota  57105
Cottonwood Hospital Medical CenterMurray, Utah  84107
Welch Cancer CenterSheridan, Wyoming  82801
Paoli Memorial HospitalPaoli, Pennsylvania  19301-1792
Front Range Cancer SpecialistsFort Collins, Colorado  80528
Poudre Valley HospitalFort Collins, Colorado  80524
Beebe Medical CenterLewes, Delaware  19958
Memorial HospitalCarthage, Illinois  62321
Mercy Hospital and Medical CenterChicago, Illinois  60616
Hematology and Oncology AssociatesChicago, Illinois  60611
Galesburg Cottage HospitalGalesburg, Illinois  61401
Galesburg ClinicGalesburg, Illinois  61401
Mason District HospitalHavana, Illinois  62644
McDonough District HospitalMacomb, Illinois  61455
BroMenn Regional Medical CenterNormal, Illinois  61761
Proctor HospitalPeoria, Illinois  61614
Perry Memorial HospitalPrinceton, Illinois  61356
Salina Regional Health CenterSalina, Kansas  67401
Bryn Mawr HospitalBryn Mawr, Pennsylvania  19010
Danville Regional Medical CenterDanville, Virginia  24541
Exempla Lutheran Medical CenterWheat Ridge, Colorado  80033
Eureka HospitalEureka, Illinois  61530
Graham Hospital AssociationCanton, Illinois  61520
Holy Family Medical CenterDes Plaines, Illinois  60016
Saint Joseph Medical CenterJoliet, Illinois  60435
Pekin HospitalPekin, Illinois  61554
Medical Oncology and Hematology AssociatesDes Moines, Iowa  50309
Geisinger Medical GroupState College, Pennsylvania  16801
Swedish American HospitalRockford, Illinois  61104
Saint Joseph HospitalChicago, Illinois  60657
Hospital District Sixth of Harper CountyAnthony, Kansas  67003
Cancer Center of Kansas - Fort ScottFort Scott, Kansas  66701
Cancer Center of Kansas-IndependenceIndependence, Kansas  67301
Lawrence Memorial HospitalLawrence, Kansas  66044
Menorah Medical CenterOverland Park, Kansas  66209
Shawnee Mission Medical CenterShawnee Mission, Kansas  66204
North Kansas City HospitalKansas City, Missouri  64116
Research Medical CenterKansas City, Missouri  64132
Saint Luke's East - Lee's SummitLee's Summit, Missouri  64086
Liberty HospitalLiberty, Missouri  64068
Heartland Regional Medical CenterSaint Joseph, Missouri  64506
Bozeman Deaconess Cancer CenterBozeman, Montana  59715
Northern Montana HospitalHavre, Montana  59501
Rocky Mountain OncologyCasper, Wyoming  82609
Longmont United HospitalLongmont, Colorado  80501
Zale Lipshy University HospitalDallas, Texas  75235-7786
Union Hospital of Cecil CountyElkton MD, Maryland  21921
Mayo Clinic in ArizonaScottsdale, Arizona  85259-5404
Sutter Roseville Medical CenterRoseville, California  95661
Memorial Medical CenterSpringfield, Illinois  62781
Guardian Oncology and Center for WellnessMissoula, Montana  59804
University of PittsburghPittsburgh, Pennsylvania  15261
Providence Medical CenterKansas City, Kansas  66112
Independence Regional Health CenterIndependence, Missouri  64050
Northwestern UniversityChicago, Illinois  60611
Saint Louis University HospitalSt. Louis, Missouri  63110-0250
Case Western Reserve UniversityCleveland, Ohio  44106
Emory UniversityAtlanta, Georgia  30322
Weiss Memorial HospitalChicago,, Illinois  60640
Presbyterian - Saint Lukes Medical Center - Health OneDenver, Colorado  80218
University of Texas Southwestern Medical CenterDallas, Texas  
Wichita CCOPWichita, Kansas  67214-3882
Montana Cancer Consortium CCOPBillings, Montana  59101
Decatur Memorial HospitalDecatur, Illinois  62526
Lankenau HospitalWynnewood, Pennsylvania  19096
Montana Cancer SpecialistsMissoula, Montana  59807-7877
Providence Saint Joseph Medical CenterBurbank, California  91505-4866
University of Chicago Comprehensive Cancer CenterChicago, Illinois  60637-1470
Wake Forest University Health SciencesWinston-Salem, North Carolina  27157
OSF Saint Francis Medical CenterPeoria, Illinois  61637
Sutter General HospitalSacramento, California  95816
The Medical Center of AuroraAurora, Colorado  80012
Penrose-Saint Francis HealthcareColorado Springs, Colorado  80907
Saint Anthony Central HospitalDenver, Colorado  80204
Exempla Saint Joseph HospitalDenver, Colorado  80218
Colorado Cancer Research Program CCOPDenver, Colorado  80224-2522
Saint Mary's Hospital and Regional Medical CenterGrand Junction, Colorado  81502
Saint Mary Corwin Medical CenterPueblo, Colorado  81004
Rush - Copley Medical CenterAurora, Illinois  60504
John H Stroger Jr Hospital of Cook CountyChicago, Illinois  60612-3785
Evanston CCOP-NorthShore University HealthSystemEvanston, Illinois  60201
Hopedale Medical Complex - HospitalHopedale, Illinois  61747
Joliet Oncology-Hematology Associates LimitedJoliet, Illinois  60435
Midwest Center for Hematology OncologyJoliet, Illinois  60432
North Shore Hematology OncologyLibertyville, Illinois  60048
Community Cancer Center FoundationNormal, Illinois  61761
Illinois CancerCare-Ottawa ClinicOttawa, Illinois  61350
Ottawa Regional Hospital and Healthcare CenterOttawa, Illinois  61350
Pekin Cancer Treatment CenterPekin, Illinois  61554
Illinois Oncology Research Association CCOPPeoria, Illinois  61615
Illinois CancerCare-PeoriaPeoria, Illinois  61615
Illinois Valley HospitalPeru, Illinois  61354
Hematology Oncology Associates of Illinois - SkokieSkokie, Illinois  60076
Edward H Kaplan MD and AssociatesSkokie, Illinois  60076
Saint Margaret's HospitalSpring Valley, Illinois  61362
Carle Clinic-Urbana MainUrbana, Illinois  61801
Fort Wayne Medical Oncology and Hematology Inc - State BoulevardFort Wayne, Indiana  46845
Saint Anthony Memorial Health CenterMichigan City, Indiana  46360
McFarland ClinicAmes, Iowa  50010
Medical Oncology and Hematology Associates-West Des MoinesClive, Iowa  50325
Iowa Oncology Research Association CCOPDes Moines, Iowa  50309
Mercy CapitolDes Moines, Iowa  50307
Mercy Medical Center - Des MoinesDes Moines, Iowa  50314
Medical Oncology and Hematology Associates-Des MoinesDes Moines, Iowa  50309
Mercy Medical Center-Sioux CitySioux City, Iowa  51104
Saint Luke's Regional Medical CenterSioux City, Iowa  51104
Cancer Center of Kansas - El DoradoEl Dorado, Kansas  67042
Cancer Center of Kansas-KingmanKingman, Kansas  67068
Radiation Oncology Practice Corporation SouthwestOverland Park, Kansas  66210
Cancer Center of Kansas - ParsonsParsons, Kansas  67357
Cancer Center of Kansas - PrattPratt, Kansas  67124
Saint Francis Hospital and Medical Center - TopekaTopeka, Kansas  66606
Cancer Center of Kansas-Wichita Medical Arts TowerWichita, Kansas  67208
Cancer Center of Kansas - Main OfficeWichita, Kansas  67214
Southeast Missouri HospitalCape Girardeau, Missouri  63701
Radiation Oncology Practice Corporation - NorthKansas City, Missouri  64154
Saint Luke's Cancer InstituteKansas City, Missouri  64111
Radiation Oncology Practice Corporation SouthKansas City, Missouri  64114
Saint Luke's Hospital of Kansas CityKansas City, Missouri  64111
Saint Joseph Health CenterKansas City, Missouri  64114
Liberty Radiation Oncology ClinicKansas City, Missouri  64116
Truman Medical CenterKansas City, Missouri  64108
Hematology-Oncology Centers of the Northern Rockies PCBillings, Montana  59101
Saint Vincent HealthcareBillings, Montana  59101
Billings ClinicBillings, Montana  59107-7000
Saint James Community Hospital and Cancer Treatment CenterButte, Montana  59701
Benefis Healthcare- Sletten Cancer InstituteGreat Falls, Montana  59405
Berdeaux, Donald MD (UIA Investigator)Great Falls, Montana  59405
Saint Peter's Community HospitalHelena, Montana  59601
Glacier Oncology PLLCKalispell, Montana  59901
Community Medical HospitalMissoula, Montana  59801
Saint Patrick Hospital - Community HospitalMissoula, Montana  59802
Ocean Medical CenterBrick, New Jersey  08724
Cooper Hospital University Medical CenterCamden, New Jersey  08103
Presbyterian Kaseman HospitalAlbuquerque, New Mexico  87110
Adirondack Cancer CenterGlens Falls, New York  12801
Orange Regional Medical CenterMiddletown, New York  10940
New York University Langone Medical CenterNew York, New York  10016
Kinston Medical Specialists PAKinston, North Carolina  28501
Scranton Hematology OncologyScranton, Pennsylvania  18510
Mercy HospitalScranton, Pennsylvania  18501
Geisinger Wyoming ValleyWilkes-Barre, Pennsylvania  18711
Mainline Health CCOPWynnewood, Pennsylvania  19096
Sanford Cancer Center-Oncology ClinicSioux Falls, South Dakota  57104
University of Maryland Greenebaum Cancer CenterBaltimore, Maryland  21201
University of IllinoisChicago, Illinois  60612
Illinois CancerCare-BloomingtonBloomington%, Illinois  61701
Illinois CancerCare-CantonCanton, Illinois  61520
Illinois CancerCare-CarthageCarthage, Illinois  62321
Jesse Brown Veterans Affairs Medical CenterChicago, Illinois  60612
Illinois CancerCare-EurekaEureka, Illinois  61530
Illinois CancerCare-HavanaHavana, Illinois  62644
Illinois CancerCare-Kewanee ClinicKewanee, Illinois  61443
Illinois CancerCare-MacombMacomb, Illinois  61455
Illinois CancerCare-MonmouthMonmouth, Illinois  61462
DuPage Medical Group-OgdenNaperville, Illinois  60563
Illinois CancerCare-Community Cancer CenterNormal, Illinois  61761
Illinois CancerCare-PekinPekin, Illinois  61603
Illinois CancerCare-PeruPeru, Illinois  61354
Illinois CancerCare-PrincetonPrinceton, Illinois  61356
Illinois CancerCare-Spring ValleySpring Valley, Illinois  61362
Cancer Center of Kansas-LiberalLiberal, Kansas  67901
University of Missouri - Ellis FischelColumbia, Missouri  65203
Veterans AdministrationColumbia, Missouri  65201
East Carolina UniversityGreenville, North Carolina  27858
University of Tennessee - KnoxvilleKnoxville, Tennessee  37920
Saint Paul HospitalDallas, Texas  75235
Medical Consultants LimitedMilwaukee, Wisconsin  53215
University of Minnesota Medical Center-FairviewMinneapolis, Minnesota  55455
Hematology Oncology Associates-BerwynBerwyn, Illinois  60402
Saint Luke's South HospitalOverland Park, Kansas  66213
Heartland Hematology and Oncology Associates IncorporatedKansas City, Missouri  64118
Saint Joseph Oncology IncSaint Joseph, Missouri  64507
Stanford University Hospitals and ClinicsStanford, California  94305
Siouxland Hematology Oncology AssociatesSioux City, Iowa  51101
Sanford Clinic North-FargoFargo, North Dakota  58102
Sanford Medical Center-FargoFargo, North Dakota  58122
Sanford USD Medical Center - Sioux FallsSioux Falls, South Dakota  57117-5134
North Shore-LIJ Health System CCOPManhasset, New York  11030
Sanford Clinic North-BemidgiBemidji, Minnesota  56601
Geisinger Medical Center-Cancer Center HazeltonHazleton, Pennsylvania  18201
Christiana Care Health System-Christiana HospitalNewark, Delaware  19718
Illinois Cancer Specialists-NilesNiles, Illinois  60714
Lake Region Healthcare Corporation-Cancer CareFergus Falls, Minnesota  56537
Los Angeles Oncology InstituteLos Angeles, California  90057