Azacitidine With or Without Entinostat in Treating Patients With Myelodysplastic Syndromes, Chronic Myelomonocytic Leukemia, or Acute Myeloid Leukemia

Sponsor
National Cancer Institute (NCI) (NIH)
Overall Status
Completed
CT.gov ID
NCT00313586
Collaborator
(none)
197
234
2
83
0.8
0

Study Details

Study Description

Brief Summary

This randomized phase II trial studies azacitidine with or without entinostat to see how well they work compared to azacitidine alone in treating patients with myelodysplastic syndromes, chronic myelomonocytic leukemia, or acute myeloid leukemia. Drugs used in chemotherapy, such as azacitidine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Entinostat may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving azacitidine together with entinostat may work better in treating patients with myelodysplastic syndromes, chronic myelomonocytic leukemia, or acute myeloid leukemia.

Detailed Description

PRIMARY OBJECTIVES:
  1. To estimate the overall response rate (complete, partial, and hematologic improvement-major by International Working Group [IWG] criteria) in response to azacitidine and entinostat.

  2. To estimate the major response rate (complete and partial responses by the IWG response criteria) to a 10-day regimen of azacitidine and to the same regimen of azacitidine in combination with entinostat administered orally on days 3 and 10 of each cycle in patients with de novo myelodysplastic syndromes (MDS), chronic myelomonocytic leukemia (CMMoL) (dysplastic) and acute myeloid leukemia with trilineage dysplasia (AML-TLD), as well as in patients with treatment-induced MDS, CMMoL (dysplastic) and AML-TLD.

SECONDARY OBJECTIVES:
  1. To evaluate the toxicity of azacitidine and entinostat in this patient population.

  2. To identify changes in gene promoter methylation and gene expression which may be associated with response to azacitidine and entinostat.

  3. To identify other molecular mechanisms (such as deoxyribonucleic acid [DNA] damage) which may be associated with response to azacitidine and entinostat.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM A: Patients receive azacitidine subcutaneously (SC) once daily (QD) on days 1-10.

ARM B: Patients receive azacitidine as in Arm A and entinostat orally (PO) on days 3 and 10.

In both arms, treatment repeats every 28 days for 6-24 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 5 years.

Study Design

Study Type:
Interventional
Actual Enrollment :
197 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
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
Study Start Date :
Aug 1, 2006
Actual Primary Completion Date :
Jul 1, 2013
Actual Study Completion Date :
Jul 1, 2013

Arms and Interventions

Arm Intervention/Treatment
Experimental: Arm A (azacitidine)

Patients receive azacitidine SC QD on days 1-10. Treatment repeats every 28 days for 6-24 courses in the absence of disease progression or unacceptable toxicity.

Drug: Azacitidine
Given SC
Other Names:
  • 5 AZC
  • 5-AC
  • 5-Azacytidine
  • 5-AZC
  • Azacytidine
  • Azacytidine, 5-
  • Ladakamycin
  • Mylosar
  • U-18496
  • Vidaza
  • Other: Laboratory Biomarker Analysis
    Correlative studies

    Experimental: Arm B (azacitidine, entinostat)

    Patients receive azacitidine as in Arm A and entinostat PO on days 3 and 10. Treatment repeats every 28 days for 6-24 courses in the absence of disease progression or unacceptable toxicity.

    Drug: Azacitidine
    Given SC
    Other Names:
  • 5 AZC
  • 5-AC
  • 5-Azacytidine
  • 5-AZC
  • Azacytidine
  • Azacytidine, 5-
  • Ladakamycin
  • Mylosar
  • U-18496
  • Vidaza
  • Drug: Entinostat
    Given PO
    Other Names:
  • HDAC inhibitor SNDX-275
  • MS 27-275
  • MS-275
  • SNDX-275
  • Other: Laboratory Biomarker Analysis
    Correlative studies

    Outcome Measures

    Primary Outcome Measures

    1. Proportion of Patients With Clinical Response [Assessed every 3 months if patient is < 2 years from study entry, every 6 months if patient is 2 - 5 years from study entry.]

      Clinical response is defined as a complete response (CR), partial response (PR) or trilineage response (TR) graded according to the following criteria: World Health Organization classification of the acute leukemias and myelodysplastic syndrome (by Bennett) Myelodysplastic syndromes standardized response criteria: further definition (by Cheson et al.) Report of an international working group to standardize response criteria for myelodysplastic syndromes (by Cheson et al.)

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • The following diagnoses will be eligible for this study:

    • Myelodysplastic syndromes: the diagnosis of MDS must be confirmed by a bone marrow aspirate and/or biopsy within two weeks prior to registration; NOTE: blast count must be < 20%; patients with any International Prognostic Score (IPSS) are eligible; patients with low or intermediate (INT)-1 IPSS must have a platelet count < 50,000/mm3 and/or absolute neutrophil count (ANC) < 500/mm3 within seven days prior to registration

    • Chronic myelomonocytic leukemia (dysplastic subtype): the diagnosis of CMMoL must be confirmed by a bone marrow aspirate and/or biopsy within two weeks prior to registration; patients with CMMoL must have a WBC < 12,000/mm^3, documented within 4 weeks prior to study entry (two sets of counts that are 2 weeks apart will be taken)

    • Acute myeloid leukemia with multilineage dysplasia: the diagnosis of AML-TLD must be confirmed by a bone marrow aspirate and/or biopsy within two weeks prior to registration; NOTE: there must be evidence of >= 20% blasts on the review of the bone marrow aspirate and/or biopsy; AML-TLD will be interpreted to include patients formerly diagnosed by French-American-British (FAB) criteria as refractory anemia with excess blasts in transformation (RAEB-t), as well as patients with no history of antecedent hematologic disorder who have AML which meets criteria for AML-TLD by World Health Organization (WHO) criteria; patients with AML-TLD must have a white blood cell (WBC) =< 30,000/mm3 documented within 4 weeks prior to study entry (two sets of counts that are 2 weeks apart will be taken); patients whose WBC has doubled within this period of time and is greater than 20,000/mm3 at the time of screening will not be eligible

    • Women must not be pregnant or breast-feeding; all females of childbearing potential must have a blood test or urine study within two weeks prior to registration to rule out pregnancy

    • Women of childbearing potential and sexually active males must be strongly advised to use an accepted and effective method of contraception

    • Patient must have Eastern Cooperative Oncology Group (ECOG) performance status between 0-2

    • Patient must have no prior treatment with azacitidine, decitabine or entinostat

    • Patients must not have active infections at the time of registration

    • Serum creatinine < 2.0 mg/dL; test must be done within seven days prior to registration

    • Total serum bilirubin within institutional limits unless due to intra- or extramedullary hemolysis or Gilbert's syndrome; test must be done within seven days prior to registration

    • Aspartate transaminase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and alanine transaminase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional upper limit of normal (ULN); tests must be done within seven days prior to registration

    • Patients must not have received any AML induction chemotherapy or stem cell transplantation; any other treatment for their disease, including hematopoietic growth factors may not be given, within three weeks prior to registration, and should have recovered from all toxicities of prior therapy (to grade 0 or 1)

    • Patients must have no clinical evidence of central nervous system (CNS) or pulmonary leukostasis, disseminated intravascular coagulation, or CNS leukemia

    • Patients must have no serious or uncontrolled medical conditions

    • Patients who have therapy-induced MDS, CMMoL (dysplastic) and AML-TLD are eligible and will be treated as separate cohorts from the patients with de novo MDS, CMMoL (dysplastic) and AML-TLD

    • Patients should have a life expectancy of at least six months

    • Patients must not have advanced malignant hepatic tumors

    • Patients must not have a known hypersensitivity to azacitidine or mannitol

    • Southwest Oncology Group (SWOG) ONLY: all SWOG patients must be registered on SWOG-9007 ("Cytogenetic Studies in Leukemia Patients"); collection of the pretreatment bone marrow specimen (or of peripheral blood if the marrow is not aspirable) must be completed within 28 days before registration; the pretreatment specimen must be submitted to a SWOG-approved cytogenetics laboratory as described in protocol SWOG-9007; note that submission of bone marrow cytogenetic studies are required to calculate the IPSS score (stratification issue); in addition, cytogenetic response will be measured at follow-up requiring a second cytogenetic study at the end of protocol treatment; NOTE: In addition to SWOG-9007, SWOG patients must be offered participation in S9910, the leukemia centralized reference laboratories and tissue repositories ancillary study; If consent is given, collection of pretreatment blood and/or marrow specimens must be completed within 14 days prior to registration. If the patient consents to participate in S9910, pretreatment specimens of marrow and/or peripheral blood must be submitted to the Southwest Oncology Group Myeloid Repository at the University of New Mexico for cellular and molecular studies; S9910 also requests submission of remission and relapse specimens

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Mayo Clinic in Arizona Scottsdale Arizona United States 85259
    2 Providence Saint Joseph Medical Center/Disney Family Cancer Center Burbank California United States 91505
    3 Los Angeles Oncology Institute Los Angeles California United States 90057
    4 Stanford Cancer Institute Palo Alto California United States 94304
    5 Sutter Roseville Medical Center Roseville California United States 95661
    6 Sutter General Hospital Sacramento California United States 95816
    7 The Medical Center of Aurora Aurora Colorado United States 80012
    8 Boulder Community Hospital Boulder Colorado United States 80301
    9 Penrose-Saint Francis Healthcare Colorado Springs Colorado United States 80907
    10 Porter Adventist Hospital Denver Colorado United States 80210
    11 Presbyterian - Saint Lukes Medical Center - Health One Denver Colorado United States 80218
    12 SCL Health Saint Joseph Hospital Denver Colorado United States 80218
    13 Rose Medical Center Denver Colorado United States 80220
    14 Colorado Cancer Research Program NCORP Denver Colorado United States 80222
    15 Swedish Medical Center Englewood Colorado United States 80113
    16 Poudre Valley Hospital Fort Collins Colorado United States 80524
    17 Front Range Cancer Specialists Fort Collins Colorado United States 80528
    18 Saint Mary's Hospital and Regional Medical Center Grand Junction Colorado United States 81502
    19 North Colorado Medical Center Greeley Colorado United States 80631
    20 Saint Anthony Hospital Lakewood Colorado United States 80228
    21 Sky Ridge Medical Center Lone Tree Colorado United States 80124
    22 Longmont United Hospital Longmont Colorado United States 80501
    23 McKee Medical Center Loveland Colorado United States 80539
    24 Saint Mary Corwin Medical Center Pueblo Colorado United States 81004
    25 North Suburban Medical Center Thornton Colorado United States 80229
    26 SCL Health Lutheran Medical Center Wheat Ridge Colorado United States 80033
    27 Beebe Medical Center Lewes Delaware United States 19958
    28 Christiana Care Health System-Christiana Hospital Newark Delaware United States 19718
    29 Sibley Memorial Hospital Washington District of Columbia United States 20016
    30 Emory University/Winship Cancer Institute Atlanta Georgia United States 30322
    31 Rush - Copley Medical Center Aurora Illinois United States 60504
    32 MacNeal Hospital and Cancer Center Berwyn Illinois United States 60402
    33 Saint Joseph Medical Center Bloomington Illinois United States 61701
    34 Illinois CancerCare-Bloomington Bloomington Illinois United States 61704
    35 Graham Hospital Association Canton Illinois United States 61520
    36 Illinois CancerCare-Canton Canton Illinois United States 61520
    37 Illinois CancerCare-Carthage Carthage Illinois United States 62321
    38 Memorial Hospital Carthage Illinois United States 62321
    39 Hematology and Oncology Associates Chicago Illinois United States 60611
    40 Northwestern University Chicago Illinois United States 60611
    41 Jesse Brown Veterans Affairs Medical Center Chicago Illinois United States 60612
    42 John H Stroger Jr Hospital of Cook County Chicago Illinois United States 60612
    43 University of Illinois Chicago Illinois United States 60612
    44 Mercy Hospital and Medical Center Chicago Illinois United States 60616
    45 University of Chicago Comprehensive Cancer Center Chicago Illinois United States 60637
    46 Weiss Memorial Hospital Chicago Illinois United States 60640
    47 Presence Saint Joseph Hospital-Chicago Chicago Illinois United States 60657
    48 Decatur Memorial Hospital Decatur Illinois United States 62526
    49 Heartland Cancer Research NCORP Decatur Illinois United States 62526
    50 Eureka Hospital Eureka Illinois United States 61530
    51 Illinois CancerCare-Eureka Eureka Illinois United States 61530
    52 NorthShore University HealthSystem-Evanston Hospital Evanston Illinois United States 60201
    53 Galesburg Cottage Hospital Galesburg Illinois United States 61401
    54 Illinois CancerCare-Galesburg Galesburg Illinois United States 61401
    55 Illinois CancerCare-Havana Havana Illinois United States 62644
    56 Mason District Hospital Havana Illinois United States 62644
    57 Hopedale Medical Complex - Hospital Hopedale Illinois United States 61747
    58 Midwest Center for Hematology Oncology Joliet Illinois United States 60432
    59 Joliet Oncology-Hematology Associates Limited Joliet Illinois United States 60435
    60 Illinois CancerCare-Kewanee Clinic Kewanee Illinois United States 61443
    61 NorthShore Hematology Oncology-Libertyville Libertyville Illinois United States 60048
    62 Illinois CancerCare-Macomb Macomb Illinois United States 61455
    63 Mcdonough District Hospital Macomb Illinois United States 61455
    64 Loyola University Medical Center Maywood Illinois United States 60153
    65 Holy Family Medical Center Monmouth Illinois United States 61462
    66 Illinois CancerCare-Monmouth Monmouth Illinois United States 61462
    67 DuPage Medical Group-Ogden Naperville Illinois United States 60563
    68 Illinois Cancer Specialists-Niles Niles Illinois United States 60714
    69 Bromenn Regional Medical Center Normal Illinois United States 61761
    70 Community Cancer Center Foundation Normal Illinois United States 61761
    71 Illinois CancerCare-Community Cancer Center Normal Illinois United States 61761
    72 Illinois CancerCare-Ottawa Clinic Ottawa Illinois United States 61350
    73 Ottawa Regional Hospital and Healthcare Center Ottawa Illinois United States 61350
    74 Illinois CancerCare-Pekin Pekin Illinois United States 61554
    75 OSF Saint Francis Radiation Oncology at Pekin Cancer Treatment Center Pekin Illinois United States 61554
    76 Pekin Hospital Pekin Illinois United States 61554
    77 Methodist Medical Center of Illinois Peoria Illinois United States 61603
    78 Proctor Hospital Peoria Illinois United States 61614
    79 Illinois CancerCare-Peoria Peoria Illinois United States 61615
    80 OSF Saint Francis Medical Center Peoria Illinois United States 61637
    81 Illinois CancerCare-Peru Peru Illinois United States 61354
    82 Illinois Valley Hospital Peru Illinois United States 61354
    83 Illinois CancerCare-Princeton Princeton Illinois United States 61356
    84 Perry Memorial Hospital Princeton Illinois United States 61356
    85 Swedish American Hospital Rockford Illinois United States 61104
    86 SwedishAmerican Regional Cancer Center/ACT Rockford Illinois United States 61114
    87 Edward H Kaplan MD and Associates Skokie Illinois United States 60076
    88 Hematology Oncology Associates of Illinois - Skokie Skokie Illinois United States 60076
    89 Illinois CancerCare-Spring Valley Spring Valley Illinois United States 61362
    90 Saint Margaret's Hospital Spring Valley Illinois United States 61362
    91 Memorial Medical Center Springfield Illinois United States 62781
    92 Carle Clinic-Urbana Main Urbana Illinois United States 61801
    93 Fort Wayne Medical Oncology and Hematology Inc-Parkview Fort Wayne Indiana United States 46845
    94 Franciscan Saint Anthony Health-Michigan City Michigan City Indiana United States 46360
    95 McFarland Clinic PC-William R Bliss Cancer Center Ames Iowa United States 50010
    96 Medical Oncology and Hematology Associates-West Des Moines Clive Iowa United States 50325
    97 Mercy Capitol Des Moines Iowa United States 50307
    98 Iowa Methodist Medical Center Des Moines Iowa United States 50309
    99 Iowa-Wide Oncology Research Coalition NCORP Des Moines Iowa United States 50309
    100 Medical Oncology and Hematology Associates-Des Moines Des Moines Iowa United States 50309
    101 Medical Oncology and Hematology Associates-Laurel Des Moines Iowa United States 50314
    102 Mercy Medical Center - Des Moines Des Moines Iowa United States 50314
    103 Iowa Lutheran Hospital Des Moines Iowa United States 50316
    104 University of Iowa/Holden Comprehensive Cancer Center Iowa City Iowa United States 52242
    105 Siouxland Regional Cancer Center Sioux City Iowa United States 51101
    106 Mercy Medical Center-Sioux City Sioux City Iowa United States 51104
    107 Saint Luke's Regional Medical Center Sioux City Iowa United States 51104
    108 Hospital District Sixth of Harper County Anthony Kansas United States 67003
    109 Cancer Center of Kansas - Chanute Chanute Kansas United States 66720
    110 Cancer Center of Kansas - Dodge City Dodge City Kansas United States 67801
    111 Cancer Center of Kansas - El Dorado El Dorado Kansas United States 67042
    112 Cancer Center of Kansas - Fort Scott Fort Scott Kansas United States 66701
    113 Cancer Center of Kansas-Independence Independence Kansas United States 67301
    114 Providence Medical Center Kansas City Kansas United States 66112
    115 Cancer Center of Kansas-Kingman Kingman Kansas United States 67068
    116 Lawrence Memorial Hospital Lawrence Kansas United States 66044
    117 Cancer Center of Kansas-Liberal Liberal Kansas United States 67905
    118 Cancer Center of Kansas - Newton Newton Kansas United States 67114
    119 Menorah Medical Center Overland Park Kansas United States 66209
    120 Radiation Oncology Practice Corporation Southwest Overland Park Kansas United States 66210
    121 Saint Luke's South Hospital Overland Park Kansas United States 66213
    122 Cancer Center of Kansas - Parsons Parsons Kansas United States 67357
    123 Kansas City NCI Community Oncology Research Program Prairie Village Kansas United States 66208
    124 Cancer Center of Kansas - Pratt Pratt Kansas United States 67124
    125 Cancer Center of Kansas - Salina Salina Kansas United States 67401
    126 Salina Regional Health Center Salina Kansas United States 67401
    127 Shawnee Mission Medical Center-KCCC Shawnee Mission Kansas United States 66204
    128 Saint Francis Hospital and Medical Center - Topeka Topeka Kansas United States 66606
    129 Cancer Center of Kansas - Wellington Wellington Kansas United States 67152
    130 Associates In Womens Health Wichita Kansas United States 67208
    131 Cancer Center of Kansas-Wichita Medical Arts Tower Wichita Kansas United States 67208
    132 Cancer Center of Kansas - Wichita Wichita Kansas United States 67214
    133 Via Christi Regional Medical Center Wichita Kansas United States 67214
    134 Wichita NCI Community Oncology Research Program Wichita Kansas United States 67214
    135 Cancer Center of Kansas - Winfield Winfield Kansas United States 67156
    136 Eastern Maine Medical Center Bangor Maine United States 04401
    137 University of Maryland/Greenebaum Cancer Center Baltimore Maryland United States 21201
    138 Johns Hopkins University/Sidney Kimmel Cancer Center Baltimore Maryland United States 21287
    139 Union Hospital of Cecil County Elkton Maryland United States 21921
    140 Boston Medical Center Boston Massachusetts United States 02118
    141 Henry Ford Hospital Detroit Michigan United States 48202
    142 Sanford Clinic North-Bemidgi Bemidji Minnesota United States 56601
    143 Lake Region Healthcare Corporation-Cancer Care Fergus Falls Minnesota United States 56537
    144 University of Minnesota/Masonic Cancer Center Minneapolis Minnesota United States 55455
    145 Mayo Clinic Rochester Minnesota United States 55905
    146 Southeast Missouri Hospital Cape Girardeau Missouri United States 63701
    147 Veterans Administration Columbia Missouri United States 65201
    148 University of Missouri - Ellis Fischel Columbia Missouri United States 65212
    149 Centerpoint Medical Center LLC Independence Missouri United States 64057
    150 Truman Medical Center Kansas City Missouri United States 64108
    151 Saint Luke's Cancer Institute Kansas City Missouri United States 64111
    152 Saint Luke's Hospital of Kansas City Kansas City Missouri United States 64111
    153 Radiation Oncology Practice Corporation South Kansas City Missouri United States 64114
    154 Saint Joseph Health Center Kansas City Missouri United States 64114
    155 North Kansas City Hospital Kansas City Missouri United States 64116
    156 Heartland Hematology and Oncology Associates Incorporated Kansas City Missouri United States 64118
    157 Research Medical Center Kansas City Missouri United States 64132
    158 Radiation Oncology Practice Corporation - North Kansas City Missouri United States 64154
    159 Saint Luke's East - Lee's Summit Lee's Summit Missouri United States 64086
    160 Liberty Hospital Liberty Missouri United States 64068
    161 Liberty Radiation Oncology Center Liberty Missouri United States 64068
    162 Heartland Regional Medical Center Saint Joseph Missouri United States 64506
    163 Saint Joseph Oncology Inc Saint Joseph Missouri United States 64507
    164 Saint Louis University Hospital Saint Louis Missouri United States 63110
    165 Billings Clinic Cancer Center Billings Montana United States 59101
    166 Montana Cancer Consortium NCORP Billings Montana United States 59101
    167 Northern Rockies Radiation Oncology Center Billings Montana United States 59101
    168 Saint Vincent Healthcare Billings Montana United States 59101
    169 Frontier Cancer Center and Blood Institute-Billings Billings Montana United States 59102
    170 Bozeman Deaconess Cancer Center Bozeman Montana United States 59715
    171 Bozeman Deaconess Hospital Bozeman Montana United States 59715
    172 Saint James Community Hospital and Cancer Treatment Center Butte Montana United States 59701
    173 Benefis Healthcare- Sletten Cancer Institute Great Falls Montana United States 59405
    174 Berdeaux, Donald MD (UIA Investigator) Great Falls Montana United States 59405
    175 Big Sky Oncology Great Falls Montana United States 59405
    176 Great Falls Clinic Great Falls Montana United States 59405
    177 Northern Montana Hospital Havre Montana United States 59501
    178 Saint Peter's Community Hospital Helena Montana United States 59601
    179 Glacier Oncology PLLC Kalispell Montana United States 59901
    180 Kalispell Medical Oncology Kalispell Montana United States 59901
    181 Kalispell Regional Medical Center Kalispell Montana United States 59901
    182 Montana Cancer Specialists Missoula Montana United States 59802
    183 Saint Patrick Hospital - Community Hospital Missoula Montana United States 59802
    184 Community Medical Hospital Missoula Montana United States 59804
    185 Guardian Oncology and Center for Wellness Missoula Montana United States 59804
    186 Ocean Medical Center Brick New Jersey United States 08724
    187 Cooper Hospital University Medical Center Camden New Jersey United States 08103
    188 Presbyterian Kaseman Hospital Albuquerque New Mexico United States 87110
    189 Montefiore Medical Center-Weiler Hospital Bronx New York United States 10461
    190 Montefiore Medical Center - Moses Campus Bronx New York United States 10467-2490
    191 Roswell Park Cancer Institute Buffalo New York United States 14263
    192 Adirondack Cancer Center Glens Falls New York United States 12801
    193 Northwell Health NCORP Lake Success New York United States 11042
    194 North Shore University Hospital Manhasset New York United States 11030
    195 Orange Regional Medical Center Middletown New York United States 10940
    196 Long Island Jewish Medical Center New Hyde Park New York United States 11040
    197 Laura and Isaac Perlmutter Cancer Center at NYU Langone New York New York United States 10016
    198 Mount Sinai Medical Center New York New York United States 10029
    199 Carolinas Medical Center/Levine Cancer Institute Charlotte North Carolina United States 28203
    200 East Carolina University Greenville North Carolina United States 27858
    201 Kinston Medical Specialists PA Kinston North Carolina United States 28501
    202 Wake Forest University Health Sciences Winston-Salem North Carolina United States 27157
    203 Sanford Clinic North-Fargo Fargo North Dakota United States 58122
    204 Sanford Medical Center-Fargo Fargo North Dakota United States 58122
    205 Akron General Medical Center Akron Ohio United States 44307
    206 Case Western Reserve University Cleveland Ohio United States 44106
    207 Bryn Mawr Hospital Bryn Mawr Pennsylvania United States 19010
    208 Geisinger Medical Center Danville Pennsylvania United States 17822
    209 Geisinger Medical Center-Cancer Center Hazleton Hazleton Pennsylvania United States 18201
    210 Paoli Memorial Hospital Paoli Pennsylvania United States 19301
    211 Fox Chase Cancer Center Philadelphia Pennsylvania United States 19111
    212 University of Pittsburgh Cancer Institute (UPCI) Pittsburgh Pennsylvania United States 15232
    213 Mercy Hospital Scranton Pennsylvania United States 18501
    214 Scranton Hematology Oncology Scranton Pennsylvania United States 18510
    215 Geisinger Medical Group State College Pennsylvania United States 16801
    216 Geisinger Wyoming Valley/Henry Cancer Center Wilkes-Barre Pennsylvania United States 18711
    217 Lankenau Medical Center Wynnewood Pennsylvania United States 19096
    218 Main Line Health NCORP Wynnewood Pennsylvania United States 19096
    219 WellSpan Health-York Hospital York Pennsylvania United States 17403
    220 Sanford Cancer Center-Oncology Clinic Sioux Falls South Dakota United States 57104
    221 Medical X-Ray Center Sioux Falls South Dakota United States 57105
    222 Sanford USD Medical Center - Sioux Falls Sioux Falls South Dakota United States 57117-5134
    223 Jackson-Madison County General Hospital Jackson Tennessee United States 38301
    224 University of Tennessee - Knoxville Knoxville Tennessee United States 37920
    225 Zale Lipshy University Hospital Dallas Texas United States 75235
    226 Clements University Hospital Dallas Texas United States 75390
    227 UT Southwestern/Simmons Cancer Center-Dallas Dallas Texas United States 75390
    228 Scott and White Memorial Hospital Temple Texas United States 76508
    229 Cottonwood Hospital Medical Center Murray Utah United States 84107
    230 Danville Regional Medical Center Danville Virginia United States 24541
    231 University of Wisconsin Hospital and Clinics Madison Wisconsin United States 53792
    232 Medical Consultants Limited Milwaukee Wisconsin United States 53215
    233 Rocky Mountain Oncology Casper Wyoming United States 82609
    234 Welch Cancer Center Sheridan Wyoming United States 82801

    Sponsors and Collaborators

    • National Cancer Institute (NCI)

    Investigators

    • Principal Investigator: Steven Gore, ECOG-ACRIN Cancer Research Group

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    National Cancer Institute (NCI)
    ClinicalTrials.gov Identifier:
    NCT00313586
    Other Study ID Numbers:
    • NCI-2009-01077
    • NCI-2009-01077
    • ECOG-E1905
    • CDR0000466186
    • E1905
    • E1905
    • U10CA180820
    • U10CA021115
    First Posted:
    Apr 12, 2006
    Last Update Posted:
    Feb 2, 2017
    Last Verified:
    Dec 1, 2016

    Study Results

    Participant Flow

    Recruitment Details Participants were recruited from ECOG member institutions between August 18, 2006 and April 29, 2011. One hundred and fifty non-treatment-induced patients and forty-seven treatment-induced patients were enrolled.
    Pre-assignment Detail
    Arm/Group Title Arm A (Azacitidine; Non-treatment-induced Cohort) Arm B (Azacitidine + Entinostat; Non-treatment-induced Cohort) Arm A (Azacitidine; Treatment-induced Cohort) Arm B (Azacitidine + Entinostat; Treatment-induced Cohort)
    Arm/Group Description Non-treatment-induced patients receive azacitidine (50 mg/m2) subcutaneously once daily on days 1-10 in a 28-day cycle. Non-treatment-induced patients receive azacitidine as in arm A and oral entinostat (4 mg/m2) on days 3 and 10 of each 28-day cycle. Treatment-induced patients receive azacitidine (50 mg/m2) subcutaneously once daily on days 1-10 in a 28-day cycle. Treatment-induced patients receive azacitidine as in arm A and oral entinostat (4 mg/m2) on days 3 and 10 of each 28-day cycle.
    Period Title: Overall Study
    STARTED 75 75 24 23
    Treated 74 75 24 23
    COMPLETED 5 5 0 0
    NOT COMPLETED 70 70 24 23

    Baseline Characteristics

    Arm/Group Title Arm A (Azacitidine; Non-treatment-induced Cohort) Arm B (Azacitidine + Entinostat; Non-treatment-induced Cohort) Arm A (Azacitidine; Treatment-induced Cohort) Arm B (Azacitidine + Entinostat; Treatment-induced Cohort) Total
    Arm/Group Description Non-treatment-induced patients receive azacitidine (50 mg/m2) subcutaneously once daily on days 1-10 in a 28-day cycle. Non-treatment-induced patients receive azacitidine as in arm A and oral entinostat (4 mg/m2) on days 3 and 10 of each 28-day cycle. Treatment-induced patients receive azacitidine (50 mg/m2) subcutaneously once daily on days 1-10 in a 28-day cycle. Treatment-induced patients receive azacitidine as in arm A and oral entinostat (4 mg/m2) on days 3 and 10 of each 28-day cycle. Total of all reporting groups
    Overall Participants 74 75 24 23 196
    Age (years) [Median (Full Range) ]
    Median (Full Range) [years]
    72
    72
    68
    71
    71
    Gender (Count of Participants)
    Female
    24
    32.4%
    23
    30.7%
    15
    62.5%
    11
    47.8%
    73
    37.2%
    Male
    50
    67.6%
    52
    69.3%
    9
    37.5%
    12
    52.2%
    123
    62.8%
    Region of Enrollment (participants) [Number]
    United States
    74
    100%
    75
    100%
    24
    100%
    23
    100%
    196
    100%

    Outcome Measures

    1. Primary Outcome
    Title Proportion of Patients With Clinical Response
    Description Clinical response is defined as a complete response (CR), partial response (PR) or trilineage response (TR) graded according to the following criteria: World Health Organization classification of the acute leukemias and myelodysplastic syndrome (by Bennett) Myelodysplastic syndromes standardized response criteria: further definition (by Cheson et al.) Report of an international working group to standardize response criteria for myelodysplastic syndromes (by Cheson et al.)
    Time Frame Assessed every 3 months if patient is < 2 years from study entry, every 6 months if patient is 2 - 5 years from study entry.

    Outcome Measure Data

    Analysis Population Description
    All treated patients are included in the analysis.
    Arm/Group Title Arm A (Azacitidine; Non-treatment-induced Cohort) Arm B (Azacitidine + Entinostat; Non-treatment-induced Cohort) Arm A (Azacitidine; Treatment-induced Cohort) Arm B (Azacitidine + Entinostat; Treatment-induced Cohort)
    Arm/Group Description Non-treatment-induced patients receive azacitidine (50 mg/m2) subcutaneously once daily on days 1-10 in a 28-day cycle. Non-treatment-induced patients receive azacitidine as in arm A and oral entinostat (4 mg/m2) on days 3 and 10 of each 28-day cycle. Treatment-induced patients receive azacitidine (50 mg/m2) subcutaneously once daily on days 1-10 in a 28-day cycle. Treatment-induced patients receive azacitidine as in arm A and oral entinostat (4 mg/m2) on days 3 and 10 of each 28-day cycle.
    Measure Participants 74 75 24 23
    Number (95% Confidence Interval) [Proportion of patients]
    0.32
    0.27
    0.46
    0.17

    Adverse Events

    Time Frame Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
    Adverse Event Reporting Description
    Arm/Group Title Arm A (Azacitidine) Arm B (Azacitidine + Entinostat)
    Arm/Group Description Patients receive azacitidine (50 mg/m2) subcutaneously once daily on days 1-10 in a 28-day cycle. Patients receive azacitidine as in arm A and oral entinostat (4 mg/m2) on days 3 and 10 of each 28-day cycle.
    All Cause Mortality
    Arm A (Azacitidine) Arm B (Azacitidine + Entinostat)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN)
    Serious Adverse Events
    Arm A (Azacitidine) Arm B (Azacitidine + Entinostat)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 92/99 (92.9%) 93/98 (94.9%)
    Blood and lymphatic system disorders
    Hemoglobin 55/99 (55.6%) 54/98 (55.1%)
    Hemolysis 0/99 (0%) 1/98 (1%)
    DIC 1/99 (1%) 0/98 (0%)
    Febrile neutropenia 20/99 (20.2%) 25/98 (25.5%)
    Cardiac disorders
    Heart block 3rd degree 0/99 (0%) 1/98 (1%)
    Atrial fibrillation 1/99 (1%) 2/98 (2%)
    Left ventricular diastolic dysfunction 0/99 (0%) 1/98 (1%)
    Pericardial effusion (non-malignant) 0/99 (0%) 1/98 (1%)
    Cardiac/heart, pain 0/99 (0%) 1/98 (1%)
    Eye disorders
    Neuropathy CN II vision 0/99 (0%) 1/98 (1%)
    Gastrointestinal disorders
    Colitis 1/99 (1%) 1/98 (1%)
    Constipation 2/99 (2%) 0/98 (0%)
    Diarrhea w/o prior colostomy 4/99 (4%) 3/98 (3.1%)
    Ileus 0/99 (0%) 1/98 (1%)
    Muco/stomatitis by exam, oral cavity 2/99 (2%) 0/98 (0%)
    Muco/stomatitis (symptom) oral cavity 1/99 (1%) 0/98 (0%)
    Nausea 2/99 (2%) 5/98 (5.1%)
    Obstruction, small bowel NOS 0/99 (0%) 1/98 (1%)
    Typhlitis 1/99 (1%) 0/98 (0%)
    Vomiting 3/99 (3%) 1/98 (1%)
    Abdomen, hemorrhage NOS 0/99 (0%) 1/98 (1%)
    Lower GI, hemorrhage NOS 0/99 (0%) 1/98 (1%)
    Oral cavity, hemorrhage 0/99 (0%) 1/98 (1%)
    Abdomen, pain 0/99 (0%) 1/98 (1%)
    General disorders
    Fatigue 10/99 (10.1%) 21/98 (21.4%)
    Constitutional, other 0/99 (0%) 1/98 (1%)
    Injection site reaction 2/99 (2%) 0/98 (0%)
    Death - multiorgan failure 1/99 (1%) 1/98 (1%)
    Death - sudden death 0/99 (0%) 1/98 (1%)
    Edema limb 0/99 (0%) 1/98 (1%)
    Chest/thoracic pain NOS 0/99 (0%) 1/98 (1%)
    Immune system disorders
    Autoimmune reaction 0/99 (0%) 1/98 (1%)
    Infections and infestations
    Colitis, infectious (e.g. C.diff) 1/99 (1%) 2/98 (2%)
    Infection w/ gr3-4 neut, abdomen NOS 1/99 (1%) 0/98 (0%)
    Infection w/ gr3-4 neut, anal/perianal 0/99 (0%) 1/98 (1%)
    Infection w/ gr3-4 neut, bronchus 1/99 (1%) 0/98 (0%)
    Infection w/ gr3-4 neut, catheter relate 2/99 (2%) 1/98 (1%)
    Infection w/ gr3-4 neut, colon 0/99 (0%) 1/98 (1%)
    Infection w/ gr3-4 neut, foreign body 1/99 (1%) 0/98 (0%)
    Infection w/ gr3-4 neut, lung 8/99 (8.1%) 9/98 (9.2%)
    Infection w/ gr3-4 neut, muscle 0/99 (0%) 1/98 (1%)
    Infection w/ gr3-4 neut, pharynx 1/99 (1%) 0/98 (0%)
    Infection w/ gr3-4 neut, sinus 1/99 (1%) 1/98 (1%)
    Infection w/ gr3-4 neut, skin 1/99 (1%) 2/98 (2%)
    Infection w/ gr3-4 neut, soft tissue NOS 0/99 (0%) 1/98 (1%)
    Infection w/ gr3-4 neut, upper airway 1/99 (1%) 1/98 (1%)
    Infection w/ gr3-4 neut, urinary tract 0/99 (0%) 2/98 (2%)
    Infection Gr0-2 neut, catheter 1/99 (1%) 0/98 (0%)
    Infection Gr0-2 neut, colon 1/99 (1%) 0/98 (0%)
    Infection Gr0-2 neut, lung 1/99 (1%) 2/98 (2%)
    Infection Gr0-2 neut, muscle 0/99 (0%) 1/98 (1%)
    Infection Gr0-2 neut, skin 1/99 (1%) 0/98 (0%)
    Infection Gr0-2 neut, urinary tract 1/99 (1%) 0/98 (0%)
    Infection Gr0-2 neut, wound 1/99 (1%) 0/98 (0%)
    Infection w/ unk ANC abdomen NOS 1/99 (1%) 0/98 (0%)
    Infection w/ unk ANC urinary tract NOS 1/99 (1%) 1/98 (1%)
    Opportunistic infection lymphopenia>=gr1 0/99 (0%) 3/98 (3.1%)
    Infection w/ gr3-4 neut, blood 2/99 (2%) 5/98 (5.1%)
    Infection Gr0-2 neut, blood 1/99 (1%) 1/98 (1%)
    Infection-other 0/99 (0%) 2/98 (2%)
    Investigations
    Leukocytes 69/99 (69.7%) 65/98 (66.3%)
    Lymphopenia 5/99 (5.1%) 7/98 (7.1%)
    Neutrophils 78/99 (78.8%) 72/98 (73.5%)
    Platelets 75/99 (75.8%) 76/98 (77.6%)
    Weight loss 0/99 (0%) 1/98 (1%)
    Coagulation-other 0/99 (0%) 1/98 (1%)
    Alkaline phosphatase 1/99 (1%) 0/98 (0%)
    ALT, SGPT 0/99 (0%) 4/98 (4.1%)
    AST, SGOT 1/99 (1%) 5/98 (5.1%)
    Bilirubin 2/99 (2%) 2/98 (2%)
    Creatinine 1/99 (1%) 3/98 (3.1%)
    Lipase 0/99 (0%) 1/98 (1%)
    Metabolism and nutrition disorders
    Anorexia 2/99 (2%) 4/98 (4.1%)
    Dehydration 2/99 (2%) 2/98 (2%)
    Hypoalbuminemia 1/99 (1%) 7/98 (7.1%)
    Hypocalcemia 0/99 (0%) 3/98 (3.1%)
    Hyperglycemia 3/99 (3%) 7/98 (7.1%)
    Hypomagnesemia 1/99 (1%) 1/98 (1%)
    Hypophosphatemia 2/99 (2%) 3/98 (3.1%)
    Hyperkalemia 0/99 (0%) 1/98 (1%)
    Hypokalemia 3/99 (3%) 2/98 (2%)
    Hyponatremia 2/99 (2%) 12/98 (12.2%)
    Hyperuricemia 1/99 (1%) 0/98 (0%)
    Musculoskeletal and connective tissue disorders
    Arthritis 0/99 (0%) 2/98 (2%)
    Nonneuropathic generalized weakness 0/99 (0%) 1/98 (1%)
    Chest wall, pain 0/99 (0%) 1/98 (1%)
    Extremity-limb, pain 1/99 (1%) 1/98 (1%)
    Joint, pain 0/99 (0%) 1/98 (1%)
    Muscle, pain 0/99 (0%) 1/98 (1%)
    Nervous system disorders
    CNS, hemorrhage 0/99 (0%) 1/98 (1%)
    Ataxia 1/99 (1%) 0/98 (0%)
    Dizziness 0/99 (0%) 1/98 (1%)
    Neuropathy-sensory 0/99 (0%) 1/98 (1%)
    Syncope 0/99 (0%) 1/98 (1%)
    Head/headache 1/99 (1%) 4/98 (4.1%)
    Psychiatric disorders
    Confusion 1/99 (1%) 1/98 (1%)
    Renal and urinary disorders
    Renal failure 0/99 (0%) 3/98 (3.1%)
    Respiratory, thoracic and mediastinal disorders
    Nose, hemorrhage 0/99 (0%) 1/98 (1%)
    Dyspnea 3/99 (3%) 5/98 (5.1%)
    Hypoxia 2/99 (2%) 1/98 (1%)
    Pulmonary/Upper Respiratory-other 0/99 (0%) 1/98 (1%)
    Skin and subcutaneous tissue disorders
    Rash/desquamation 0/99 (0%) 2/98 (2%)
    Rash: acne/acneiform 0/99 (0%) 1/98 (1%)
    Vascular disorders
    Hypotension 4/99 (4%) 3/98 (3.1%)
    Visceral arterial ischemia 0/99 (0%) 1/98 (1%)
    Other (Not Including Serious) Adverse Events
    Arm A (Azacitidine) Arm B (Azacitidine + Entinostat)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 96/99 (97%) 97/98 (99%)
    Blood and lymphatic system disorders
    Hemoglobin 80/99 (80.8%) 74/98 (75.5%)
    Gastrointestinal disorders
    Constipation 37/99 (37.4%) 39/98 (39.8%)
    Diarrhea w/o prior colostomy 28/99 (28.3%) 40/98 (40.8%)
    Dyspepsia 7/99 (7.1%) 10/98 (10.2%)
    Muco/stomatitis by exam, oral cavity 4/99 (4%) 5/98 (5.1%)
    Nausea 49/99 (49.5%) 55/98 (56.1%)
    Vomiting 22/99 (22.2%) 30/98 (30.6%)
    Abdomen, pain 9/99 (9.1%) 13/98 (13.3%)
    General disorders
    Fatigue 71/99 (71.7%) 71/98 (72.4%)
    Fever w/o neutropenia 10/99 (10.1%) 7/98 (7.1%)
    Rigors/chills 4/99 (4%) 5/98 (5.1%)
    Injection site reaction 41/99 (41.4%) 42/98 (42.9%)
    Edema limb 7/99 (7.1%) 23/98 (23.5%)
    Injury, poisoning and procedural complications
    Bruising 6/99 (6.1%) 6/98 (6.1%)
    Investigations
    Leukocytes 67/99 (67.7%) 57/98 (58.2%)
    Lymphopenia 11/99 (11.1%) 8/98 (8.2%)
    Neutrophils 56/99 (56.6%) 49/98 (50%)
    Platelets 63/99 (63.6%) 57/98 (58.2%)
    Weight loss 8/99 (8.1%) 15/98 (15.3%)
    Alkaline phosphatase 11/99 (11.1%) 17/98 (17.3%)
    ALT, SGPT 15/99 (15.2%) 12/98 (12.2%)
    AST, SGOT 14/99 (14.1%) 11/98 (11.2%)
    Bilirubin 11/99 (11.1%) 11/98 (11.2%)
    Creatinine 18/99 (18.2%) 26/98 (26.5%)
    Metabolism and nutrition disorders
    Anorexia 27/99 (27.3%) 49/98 (50%)
    Dehydration 3/99 (3%) 9/98 (9.2%)
    Hypoalbuminemia 22/99 (22.2%) 41/98 (41.8%)
    Hypocalcemia 16/99 (16.2%) 42/98 (42.9%)
    Hyperglycemia 30/99 (30.3%) 40/98 (40.8%)
    Hypomagnesemia 3/99 (3%) 5/98 (5.1%)
    Hypophosphatemia 2/99 (2%) 8/98 (8.2%)
    Hypokalemia 7/99 (7.1%) 14/98 (14.3%)
    Hyponatremia 24/99 (24.2%) 36/98 (36.7%)
    Musculoskeletal and connective tissue disorders
    Nonneuropathic generalized weakness 1/99 (1%) 7/98 (7.1%)
    Joint, pain 3/99 (3%) 10/98 (10.2%)
    Muscle, pain 1/99 (1%) 7/98 (7.1%)
    Nervous system disorders
    Taste disturbance 9/99 (9.1%) 18/98 (18.4%)
    Dizziness 3/99 (3%) 11/98 (11.2%)
    Neuropathy-sensory 2/99 (2%) 8/98 (8.2%)
    Head/headache 9/99 (9.1%) 16/98 (16.3%)
    Psychiatric disorders
    Insomnia 8/99 (8.1%) 10/98 (10.2%)
    Respiratory, thoracic and mediastinal disorders
    Allergic rhinitis 5/99 (5.1%) 4/98 (4.1%)
    Nose, hemorrhage 3/99 (3%) 12/98 (12.2%)
    Cough 6/99 (6.1%) 9/98 (9.2%)
    Dyspnea 15/99 (15.2%) 22/98 (22.4%)
    Skin and subcutaneous tissue disorders
    Sweating 6/99 (6.1%) 6/98 (6.1%)
    Alopecia 6/99 (6.1%) 9/98 (9.2%)
    Pruritus/itching 5/99 (5.1%) 7/98 (7.1%)
    Rash/desquamation 11/99 (11.1%) 13/98 (13.3%)
    Petechiae 4/99 (4%) 9/98 (9.2%)
    Vascular disorders
    Hypotension 2/99 (2%) 8/98 (8.2%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.

    Results Point of Contact

    Name/Title Study Statistician
    Organization ECOG Statistical Office
    Phone 617-632-3012
    Email
    Responsible Party:
    National Cancer Institute (NCI)
    ClinicalTrials.gov Identifier:
    NCT00313586
    Other Study ID Numbers:
    • NCI-2009-01077
    • NCI-2009-01077
    • ECOG-E1905
    • CDR0000466186
    • E1905
    • E1905
    • U10CA180820
    • U10CA021115
    First Posted:
    Apr 12, 2006
    Last Update Posted:
    Feb 2, 2017
    Last Verified:
    Dec 1, 2016