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Azacitidine With or Without Lenalidomide or Vorinostat in Treating Patients With Higher-Risk Myelodysplastic Syndromes or Chronic Myelomonocytic Leukemia

Sponsor
National Cancer Institute (NCI) (NIH)
Overall Status
Active, not recruiting
CT.gov ID
NCT01522976
Collaborator
(none)
282
Enrollment
298
Locations
3
Arms
0.9
Patients Per Site

Study Details

Study Description

Brief Summary

This randomized phase II/III trial studies how well azacitidine works with or without lenalidomide or vorinostat in treating patients with higher-risk myelodysplastic syndromes or chronic myelomonocytic leukemia. Drugs used in chemotherapy, such as azacitidine, work in different ways to stop the growth of cancer cells, either by killing the cells, stopping them from dividing, or by stopping them from spreading. Lenalidomide may stop the growth of cancer cells by stopping blood flow to the cancer. Vorinostat may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. It is not yet known whether azacitidine is more effective with or without lenalidomide or vorinostat in treating myelodysplastic syndromes or chronic myelomonocytic leukemia.

Condition or Disease Intervention/Treatment Phase
Phase 2

Detailed Description

PRIMARY OBJECTIVES:
  1. To select based on response rate (complete remission, partial remission, or hematologic improvement) either the combination of lenalidomide and azacitidine or the combination of vorinostat and azacitidine for further testing against single-agent azacitidine among patients with higher-risk myelodysplastic syndromes (MDS) or chronic myelomonocytic leukemia (CMML). (Phase II) II. To compare overall survival between the combination arm selected in the Phase II portion of the trial to single-agent azacitidine among patients with higher-risk myelodysplastic syndromes (MDS) or chronic myelomonocytic leukemia (CMML). (Phase III)
SECONDARY OBJECTIVES:

  1. To estimate relapse-free survival, overall survival and cytogenetic response rate of patients treated on each regimen.

  2. To estimate the frequency and severity of toxicities of the three regimens in this patient population.

  3. To investigate in a preliminary manner the frequency of subgroups from prestudy cytogenetic studies and correlate these subgroups with clinical outcomes in this patient population.

  4. To collect specimens for banking for use in future research studies.

TERTIARY OBJECTIVES:

  1. To evaluate the prevalence of a pre-specified list of molecular lesions (48 total lesions).

  2. To assess associations of these lesions with outcomes (response, event-free survival, relapse-free survival, and overall survival).

  3. To develop a deoxyribonucleic acid (DNA) methylation biomarker predictive of response to DMTi treatment in MDS.

  4. To harness gene expression profiles as clinical biomarkers of primary resistance to DMTi in MDS.

OUTLINE: Patients are randomized to 1 of 3 treatment arms. In Phase III, patients are randomized to 1 of 2 treatment arms (the combination arm selected in Phase II or the single-agent azacitidine arm).

ARM I: Patients receive azacitidine subcutaneously (SC) or intravenously (IV) on days 1-7 or days 1-5 and 8-9, and lenalidomide orally (PO) once daily (QD) on days 1-21.

ARM II: Patients receive azacitidine as in Arm I.

ARM III: Patients receive azacitidine as in Arm I and vorinostat PO twice daily (BID) on days 3-9.

In all arms, treatment repeats every 28 days for up to 5 years in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for up to 5 years.

Study Design

Study Type:
Interventional
Actual Enrollment :
282 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Randomized Phase II/III Study of Azacitidine in Combination With Lenalidomide (NSC-703813) vs. Azacitidine Alone vs. Azacitidine in Combination With Vorinostat (NSC-701852) for Higher-Risk Myelodysplastic Syndromes (MDS) and Chronic Myelomonocytic Leukemia (CMML)
Actual Study Start Date :
Mar 1, 2012
Actual Primary Completion Date :
Jun 1, 2015

Arms and Interventions

Arm Intervention/Treatment
Experimental: Arm I (azacitidine and lenalidomide)

Patients receive azacitidine SC or IV on days 1-7 or days 1-5 and 8-9, and lenalidomide PO QD on days 1-21. Courses repeat every 28 days for up to 5 years in the absence of disease progression or unacceptable toxicity.

Drug: Azacitidine
Given SC or IV
Other Names:
  • 5 AZC
  • 5-AC
  • 5-Azacytidine
  • 5-AZC
  • Azacytidine
  • Azacytidine, 5-
  • Ladakamycin
  • Mylosar
  • Onureg
  • U-18496
  • Vidaza

    • Other: Laboratory Biomarker Analysis
    Correlative studies

    Drug: Lenalidomide
    Given PO
    Other Names:
  • CC-5013
  • CC5013
  • CDC 501
  • Revlimid

    		•
    Experimental: Arm II (azacitidine)

    Patients receive azacitidine as in Arm I. Courses repeat every 28 days for up to 5 years in the absence of disease progression or unacceptable toxicity.

    Drug: Azacitidine
    Given SC or IV
    Other Names:
  • 5 AZC
  • 5-AC
  • 5-Azacytidine
  • 5-AZC
  • Azacytidine
  • Azacytidine, 5-
  • Ladakamycin
  • Mylosar
  • Onureg
  • U-18496
  • Vidaza

    • Other: Laboratory Biomarker Analysis
    Correlative studies
    Experimental: Arm III (azacitidine and vorinostat)

    Patients receive azacitidine as in Arm I and vorinostat PO BID on days 3-9. Courses repeat every 28 days for up to 5 years in the absence of disease progression or unacceptable toxicity.

    Drug: Azacitidine
    Given SC or IV
    Other Names:
  • 5 AZC
  • 5-AC
  • 5-Azacytidine
  • 5-AZC
  • Azacytidine
  • Azacytidine, 5-
  • Ladakamycin
  • Mylosar
  • Onureg
  • U-18496
  • Vidaza

    • Other: Laboratory Biomarker Analysis
    Correlative studies

    Drug: Vorinostat
    Given PO
    Other Names:
  • L-001079038
  • MSK-390
  • SAHA
  • Suberanilohydroxamic Acid
  • Suberoylanilide Hydroxamic Acid
  • Zolinza

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Response Rate (Phase II) [Up to 5 years]

      A response is any of complete hematological remission, partial remission, or hematologic improvement.

    2. Overall Survival (Phase III) [Up to 5 years]

      OS is calculated for all patients from the date of initial registration to date of death due to any cause. The follow-up for patients last known to be alive is censored at the date of last contact. Stratified Cox regression models will be used to compare OS of the combination arm selected in the Phase II portion of the trial to OS of the single-agent azacitidine arm.

    Secondary Outcome Measures

    1. Relapse-free Survival [Up to 5 years]

      RFS is calculated for patients who have achieved a response. RFS will be measured from the date of response to the date of first documentation of relapse from response (as defined in the primary objective), or death due to any cause. The follow-up for patients last known to be alive and without report of relapse is censored at the date of last contact. RFS will be estimated for each of the three arms using the Kaplan-Meier method.

    2. Overall Survival [Up to 5 years]

      OS is calculated for all patients from the date of initial registration to date of death due to any cause. The follow- up for patients last known to be alive is censored at the date of last contact. OS will be estimated for each of the three arms using the Kaplan-Meier method.

    3. Pre-study Cytogenetic Abnormalities [Up to 5 years]

      Cytogenetic risk group is used to identify cytogenetic abnormalities.

    4. Toxicity Rate [Up to 5 years]

      Adverse events that are possibly, probably or definitely related to study drug are reported.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • Patients must have morphologically confirmed diagnosis of myelodysplastic syndrome (MDS) or chronic myelomonocytic leukemia (CMML) based on one of the following:

    • French-American-British (FAB) classifications:

    • Refractory anemia with excess blasts (RAEB - defined as having 5-20% myeloblasts in the bone marrow)

    • Chronic myelomonocytic leukemia (CMML) with 10-19% myeloblasts in the bone marrow and/or 5-19% blasts in the blood

    • World Health Organization (WHO) classifications:

    • Refractory anemia with excess blasts-1 (RAEB-1 - defined as having 5-9% myeloblasts in the bone marrow)

    • Refractory anemia with excess blasts-2 (RAEB-2 - defined as having 10-19% myeloblasts in the bone marrow and/or 5-19% blasts in the blood)

    • Chronic myelomonocytic leukemia-1 (CMML-1 - defined as having < 10% myeloblasts in the bone marrow and/or < 5% blasts in the blood)

    • Chronic myelomonocytic leukemia-2 (CMML-2 - defined as having 10-19% myeloblasts in the bone marrow and/or 5-19% blasts in the blood) OR

    • International prognostic score (IPSS) of intermediate 2 (1.5-2.0 points) or high (>= 2.5 points); a score of intermediate 1 (0.5-1.0 points) is only allowable in the setting of >= 5% myeloblasts

    • NOTE: Patients with acute myeloid leukemia (AML) are not eligible

    • Procedures to obtain specimens for establishing baseline disease must be done within 30 days prior to registration

    • Patients must not have received lenalidomide, azacitidine, vorinostat, or decitabine as treatment previously; any hematopoietic growth factors must be stopped for at least 14 days prior to registration; patients may have received low-dose cytarabine for MDS treatment previously, but they must have discontinued its use for at least 28 days prior to registration; patients may have received prior hydroxyurea per CMML treatment previously, but they must have discontinued its use for at least 7 days prior to registration; these patients will not be eligible if white blood cell (WBC) > 30,000/mm^3

    • Patients must not have received radiation therapy, chemotherapy, or cytotoxic therapy to treat conditions other than MDS within 12 months prior to registration

    • Patients must not have undergone prior allogeneic stem cell or bone marrow transplantation at any time; patients that have undergone an autologous stem cell transplant are eligible

    • Patients must not have used or be using histone deacetylase (HDAC) inhibitor agents for anticancer treatment

    • Patients may not have received agents such as valproic acid for epilepsy within 30 days prior to registration

    • Patients must have Zubrod performance status of 0-2

    • Patients must not have any pre-existing neurotoxicity/neuropathy of >= grade 2 according to the National Cancer Institute (NCI) Common Toxicity Criteria version 4.0, or prior >= grade 3 allergic reaction/hypersensitivity or rash to thalidomide, that has not resolved to < grade 2

    • Patients must not have any serious medical condition, laboratory abnormality, or psychiatric illness that, in the view of the treating physician, would place the participant at an unacceptable risk if he or she were to participate in the study or would prevent that person from giving informed consent

    • Patients must not have history of thromboembolic event or other condition requiring current use of anticoagulation with Coumadin (warfarin) or low molecular-weight heparin

    • Patients must not have known or suspected hypersensitivity to mannitol

    • Patients must receive a 12-lead electrocardiogram (EKG), chest x-ray or computed tomography (CT) scan, serum creatinine, complete metabolic panel including serum glutamic oxaloacetic transaminase (SGOT) or serum glutamate pyruvate transaminase (SGPT), electrolytes, and bilirubin testing within 28 days prior to registration in order to establish baseline measurements; questions regarding patient safety in regards to results of these tests should be directed to the study chair

    • Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test with a sensitivity of at least 25 mIU/mL within 10 - 14 days prior to registration; FCBP must agree to have a second pregnancy test within 24 hours prior to starting cycle 1 if randomized to receive lenalidomide

    • Further, patients commit to the following if they are randomized to receive lenalidomide: FCBP must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control: one highly effective method and one additional effective method AT THE SAME TIME, at least 28 days before starting lenalidomide; FCBP must also agree to ongoing pregnancy testing; men must agree to use a latex condom during sexual contact with a FCBP, even if they have had a successful vasectomy; a FCBP is a sexually mature woman who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months); all patients must be counseled by a trained counselor every 28 days about pregnancy precautions and risks of fetal exposure

    • NOTE: Patients not randomized to receive lenalidomide will not be required to undergo serial pregnancy testing or lenalidomide counseling after registration

    • No prior malignancy is allowed except for adequately treated basal cell (or squamous cell) skin cancer, in situ cervical cancer, or other cancer for which the patient has been disease-free for three years

    • Cytogenetics requirements:

    • Southwestern Oncology Group (SWOG) (and other sites not affiliated with Alliance or Eastern Cooperative Oncology Group [ECOG]-American College of Radiology Imaging Network [ACRIN]): Pretreatment cytogenetics must be performed on all patients; collection of pretreatment specimens must be completed within 30 days prior to registration to S1117; specimens must be submitted to the site's preferred Clinical Laboratory Improvement Amendments (CLIA)-approved cytogenetics laboratory; reports of the results must be submitted as described; note that cytogenetics are required at other timepoints; NOTE: National Cancer Institute of Canada Clinical Trials Group (NCIC CTG) sites may submit specimens to College of American Pathologists (CAP) or Ontario Laboratory Accreditation (OLA)-approved laboratories providing the lab is licensed to perform fluorescent in situ hybridization (FISH) analysis

    • Alliance: Alliance patients must enroll on Cancer and Leukemia Group B (CALGB) 8461, the cytogenetics protocol; CALGB 8461 provides sample procurement and submission instructions to Alliance-approved institutional cytogeneticists; note that cytogenetics are required at other timepoints

    • ECOG-ACRIN: Pretreatment cytogenetics must be performed on all patients; collection of pretreatment specimens must be completed within 30 days prior to registration to S1117; specimens must be submitted to the site's preferred CLIA-approved cytogenetics laboratory; karyotypes and reports must be submitted for review to the Mayo Clinic Cytogenetics Laboratory in Rochester; note that cytogenetics testing is required at other timepoints

    • Banking requirements:

    • SWOG, Alliance and ECOG-ACRIN (and other sites not affiliated with NCIC CTG): Patients must be offered participation in specimen banking; with patient consent, specimens must be submitted as outlined

    • Alliance: (Temporarily Closed 2/28/14): As of February 28, 2014, CALGB 9665 has been temporarily closed, so Alliance patients under consideration for S1117 are NOT to be registered to CALGB 9665 and no specimens for patients enrolled after February 28, 2014 are to be submitted via this ancillary study; these patients should submit specimens per SWOG instructions; patients already enrolled on CALGB 9665 should continue to submit specimens per instructions in CALGB 9665

    • NCIC CTG: NCIC CTG patients must be offered participation in specimen submission and banking; with patient consent, specimens must be submitted as outlined

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

    • As a part of the Oncology Patient Enrollment Network (OPEN) registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 University of Alabama at Birmingham Cancer Center Birmingham Alabama United States 35233
    2 University of South Alabama Mitchell Cancer Institute Mobile Alabama United States 36688
    3 Mayo Clinic in Arizona Scottsdale Arizona United States 85259
    4 Banner University Medical Center - Tucson Tucson Arizona United States 85719
    5 University of Arizona Cancer Center-North Campus Tucson Arizona United States 85719
    6 John L McClellan Memorial Veterans Hospital Little Rock Arkansas United States 72205
    7 Kaiser Permanente-Deer Valley Medical Center Antioch California United States 94531
    8 City of Hope Comprehensive Cancer Center Duarte California United States 91010
    9 USC / Norris Comprehensive Cancer Center Los Angeles California United States 90033
    10 Kaiser Permanente-Oakland Oakland California United States 94611
    11 Stanford Cancer Institute Palo Alto Palo Alto California United States 94304
    12 Kaiser Permanente-Richmond Richmond California United States 94801
    13 Kaiser Permanente-South Sacramento Sacramento California United States 95823
    14 Kaiser Permanente - Sacramento Sacramento California United States 95825
    15 Kaiser Permanente-San Francisco San Francisco California United States 94115
    16 Kaiser Permanente-Santa Teresa-San Jose San Jose California United States 95119
    17 Kaiser Permanente-San Rafael San Rafael California United States 94903
    18 Kaiser Permanente Medical Center - Santa Clara Santa Clara California United States 95051
    19 Kaiser Permanente-Santa Rosa Santa Rosa California United States 95403
    20 Sutter Pacific Medical Foundation Santa Rosa California United States 95403
    21 Kaiser Permanente-South San Francisco South San Francisco California United States 94080
    22 Kaiser Permanente-Vallejo Vallejo California United States 94589
    23 Kaiser Permanente-Walnut Creek Walnut Creek California United States 94596
    24 The Medical Center of Aurora Aurora Colorado United States 80012
    25 University of Colorado Hospital Aurora Colorado United States 80045
    26 Boulder Community Hospital Boulder Colorado United States 80301
    27 Penrose-Saint Francis Healthcare Colorado Springs Colorado United States 80907
    28 Porter Adventist Hospital Denver Colorado United States 80210
    29 Colorado Blood Cancer Institute Denver Colorado United States 80218
    30 Presbyterian - Saint Lukes Medical Center - Health One Denver Colorado United States 80218
    31 Rocky Mountain Cancer Centers-Midtown Denver Colorado United States 80218
    32 SCL Health Saint Joseph Hospital Denver Colorado United States 80218
    33 Rocky Mountain Cancer Centers-Rose Denver Colorado United States 80220
    34 Rose Medical Center Denver Colorado United States 80220
    35 Western States Cancer Research NCORP Denver Colorado United States 80222
    36 Mercy Medical Center Durango Colorado United States 81301
    37 Mountain Blue Cancer Care Center - Swedish Englewood Colorado United States 80113
    38 Swedish Medical Center Englewood Colorado United States 80113
    39 Poudre Valley Hospital Fort Collins Colorado United States 80524
    40 Mountain Blue Cancer Care Center Golden Colorado United States 80401
    41 North Colorado Medical Center Greeley Colorado United States 80631
    42 Rocky Mountain Cancer Centers-Greenwood Village Greenwood Village Colorado United States 80111
    43 Rocky Mountain Cancer Centers-Lakewood Lakewood Colorado United States 80228
    44 Saint Anthony Hospital Lakewood Colorado United States 80228
    45 Littleton Adventist Hospital Littleton Colorado United States 80122
    46 Rocky Mountain Cancer Centers-Sky Ridge Lone Tree Colorado United States 80124
    47 Sky Ridge Medical Center Lone Tree Colorado United States 80124
    48 Longmont United Hospital Longmont Colorado United States 80501
    49 McKee Medical Center Loveland Colorado United States 80539
    50 Parker Adventist Hospital Parker Colorado United States 80138
    51 Rocky Mountain Cancer Centers-Parker Parker Colorado United States 80138
    52 Saint Mary Corwin Medical Center Pueblo Colorado United States 81004
    53 SCL Health Lutheran Medical Center Wheat Ridge Colorado United States 80033
    54 University of Connecticut Farmington Connecticut United States 06030
    55 Smilow Cancer Hospital Care Center at Saint Francis Hartford Connecticut United States 06105
    56 The Hospital of Central Connecticut New Britain Connecticut United States 06050
    57 Beebe Medical Center Lewes Delaware United States 19958
    58 Christiana Care Health System-Christiana Hospital Newark Delaware United States 19718
    59 Sibley Memorial Hospital Washington District of Columbia United States 20016
    60 Veterans Affairs Medical Center -Washington DC Washington District of Columbia United States 20422
    61 University of Florida Health Science Center - Gainesville Gainesville Florida United States 32610
    62 Jupiter Medical Center Jupiter Florida United States 33458
    63 Mount Sinai Medical Center Miami Beach Florida United States 33140
    64 AdventHealth Orlando Orlando Florida United States 32803
    65 Augusta University Medical Center Augusta Georgia United States 30912
    66 Hawaii Cancer Care Inc - Waterfront Plaza Honolulu Hawaii United States 96813
    67 Straub Clinic and Hospital Honolulu Hawaii United States 96813
    68 University of Hawaii Cancer Center Honolulu Hawaii United States 96813
    69 Queen's Cancer Center - Kuakini Honolulu Hawaii United States 96817
    70 Kaiser Permanente Moanalua Medical Center Honolulu Hawaii United States 96819
    71 Saint Alphonsus Cancer Care Center-Boise Boise Idaho United States 83706
    72 Kootenai Clinic Cancer Services - Post Falls Post Falls Idaho United States 83854
    73 Illinois CancerCare-Bloomington Bloomington Illinois United States 61704
    74 Illinois CancerCare-Canton Canton Illinois United States 61520
    75 Illinois CancerCare-Carthage Carthage Illinois United States 62321
    76 Hematology and Oncology Associates Chicago Illinois United States 60611
    77 Northwestern University Chicago Illinois United States 60611
    78 University of Illinois Chicago Illinois United States 60612
    79 University of Chicago Comprehensive Cancer Center Chicago Illinois United States 60637
    80 Decatur Memorial Hospital Decatur Illinois United States 62526
    81 Heartland Cancer Research NCORP Decatur Illinois United States 62526
    82 Illinois CancerCare-Eureka Eureka Illinois United States 61530
    83 NorthShore University HealthSystem-Evanston Hospital Evanston Illinois United States 60201
    84 Illinois CancerCare-Galesburg Galesburg Illinois United States 61401
    85 Illinois CancerCare-Havana Havana Illinois United States 62644
    86 Illinois CancerCare-Kewanee Clinic Kewanee Illinois United States 61443
    87 Illinois CancerCare-Macomb Macomb Illinois United States 61455
    88 Loyola University Medical Center Maywood Illinois United States 60153
    89 Trinity Medical Center Moline Illinois United States 61265
    90 Illinois CancerCare-Monmouth Monmouth Illinois United States 61462
    91 Illinois CancerCare-Community Cancer Center Normal Illinois United States 61761
    92 Illinois CancerCare-Ottawa Clinic Ottawa Illinois United States 61350
    93 Illinois CancerCare-Pekin Pekin Illinois United States 61554
    94 Illinois CancerCare-Peoria Peoria Illinois United States 61615
    95 Illinois CancerCare-Peru Peru Illinois United States 61354
    96 Illinois CancerCare-Princeton Princeton Illinois United States 61356
    97 Swedish American Hospital Rockford Illinois United States 61104
    98 SwedishAmerican Regional Cancer Center/ACT Rockford Illinois United States 61114
    99 Memorial Medical Center Springfield Illinois United States 62781
    100 Carle Cancer Center Urbana Illinois United States 61801
    101 Premier Oncology Hematology Associates Merrillville Indiana United States 46410
    102 McFarland Clinic PC - Ames Ames Iowa United States 50010
    103 University of Iowa/Holden Comprehensive Cancer Center Iowa City Iowa United States 52242
    104 Siouxland Regional Cancer Center Sioux City Iowa United States 51101
    105 MercyOne Waterloo Medical Center Waterloo Iowa United States 50702
    106 University of Kansas Cancer Center Kansas City Kansas United States 66160
    107 Kansas City NCI Community Oncology Research Program Prairie Village Kansas United States 66208
    108 Cotton O'Neil Cancer Center / Stormont Vail Health Topeka Kansas United States 66606
    109 University of Kentucky/Markey Cancer Center Lexington Kentucky United States 40536
    110 Ochsner Health Center-Summa Baton Rouge Louisiana United States 70809
    111 Ochsner Medical Center Jefferson New Orleans Louisiana United States 70121
    112 LSU Health Sciences Center at Shreveport Shreveport Louisiana United States 71103
    113 Eastern Maine Medical Center Bangor Maine United States 04401
    114 Johns Hopkins University/Sidney Kimmel Cancer Center Baltimore Maryland United States 21287
    115 Christiana Care - Union Hospital Elkton Maryland United States 21921
    116 Massachusetts General Hospital Cancer Center Boston Massachusetts United States 02114
    117 Dana-Farber Cancer Institute Boston Massachusetts United States 02215
    118 Steward Saint Elizabeth's Medical Center Brighton Massachusetts United States 02135
    119 Baystate Medical Center Springfield Massachusetts United States 01199
    120 UMass Memorial Medical Center - University Campus Worcester Massachusetts United States 01655
    121 Michigan Cancer Research Consortium NCORP Ann Arbor Michigan United States 48106
    122 Saint Joseph Mercy Hospital Ann Arbor Michigan United States 48106
    123 Bronson Battle Creek Battle Creek Michigan United States 49017
    124 Wayne State University/Karmanos Cancer Institute Detroit Michigan United States 48201
    125 Ascension Saint John Hospital Detroit Michigan United States 48236
    126 Green Bay Oncology - Escanaba Escanaba Michigan United States 49829
    127 Cancer Research Consortium of West Michigan NCORP Grand Rapids Michigan United States 49503
    128 Mercy Health Saint Mary's Grand Rapids Michigan United States 49503
    129 Spectrum Health at Butterworth Campus Grand Rapids Michigan United States 49503
    130 Green Bay Oncology - Iron Mountain Iron Mountain Michigan United States 49801
    131 West Michigan Cancer Center Kalamazoo Michigan United States 49007
    132 Mercy Health Mercy Campus Muskegon Michigan United States 49444
    133 Lake Huron Medical Center Port Huron Michigan United States 48060
    134 Spectrum Health Reed City Hospital Reed City Michigan United States 49677
    135 Munson Medical Center Traverse City Michigan United States 49684
    136 Saint John Macomb-Oakland Hospital Warren Michigan United States 48093
    137 Sanford Joe Lueken Cancer Center Bemidji Minnesota United States 56601
    138 Fairview Ridges Hospital Burnsville Minnesota United States 55337
    139 Mercy Hospital Coon Rapids Minnesota United States 55433
    140 Essentia Health Cancer Center Duluth Minnesota United States 55805
    141 Fairview Southdale Hospital Edina Minnesota United States 55435
    142 Unity Hospital Fridley Minnesota United States 55432
    143 Hutchinson Area Health Care Hutchinson Minnesota United States 55350
    144 Minnesota Oncology Hematology PA-Maplewood Maplewood Minnesota United States 55109
    145 Saint John's Hospital - Healtheast Maplewood Minnesota United States 55109
    146 Abbott-Northwestern Hospital Minneapolis Minnesota United States 55407
    147 Hennepin County Medical Center Minneapolis Minnesota United States 55415
    148 Minneapolis VA Medical Center Minneapolis Minnesota United States 55417
    149 North Memorial Medical Health Center Robbinsdale Minnesota United States 55422
    150 Mayo Clinic in Rochester Rochester Minnesota United States 55905
    151 Coborn Cancer Center at Saint Cloud Hospital Saint Cloud Minnesota United States 56303
    152 Metro Minnesota Community Oncology Research Consortium Saint Louis Park Minnesota United States 55416
    153 Park Nicollet Clinic - Saint Louis Park Saint Louis Park Minnesota United States 55416
    154 Regions Hospital Saint Paul Minnesota United States 55101
    155 United Hospital Saint Paul Minnesota United States 55102
    156 Saint Francis Regional Medical Center Shakopee Minnesota United States 55379
    157 Lakeview Hospital Stillwater Minnesota United States 55082
    158 Ridgeview Medical Center Waconia Minnesota United States 55387
    159 Rice Memorial Hospital Willmar Minnesota United States 56201
    160 Minnesota Oncology Hematology PA-Woodbury Woodbury Minnesota United States 55125
    161 University of Mississippi Medical Center Jackson Mississippi United States 39216
    162 Saint Francis Medical Center Cape Girardeau Missouri United States 63703
    163 Veterans Administration Columbia Missouri United States 65201
    164 University of Missouri - Ellis Fischel Columbia Missouri United States 65212
    165 Saint Luke's Hospital of Kansas City Kansas City Missouri United States 64111
    166 Mercy Hospital Saint Louis Saint Louis Missouri United States 63141
    167 Saint Louis-Cape Girardeau CCOP Saint Louis Missouri United States 63141
    168 Billings Clinic Cancer Center Billings Montana United States 59101
    169 Bozeman Deaconess Hospital Bozeman Montana United States 59715
    170 Cooper Hospital University Medical Center Camden New Jersey United States 08103
    171 University of New Mexico Cancer Center Albuquerque New Mexico United States 87102
    172 Presbyterian Kaseman Hospital Albuquerque New Mexico United States 87110
    173 Montefiore Medical Center-Weiler Hospital Bronx New York United States 10461
    174 Montefiore Medical Center - Moses Campus Bronx New York United States 10467
    175 Roswell Park Cancer Institute Buffalo New York United States 14263
    176 Northwell Health/Center for Advanced Medicine Lake Success New York United States 11042
    177 North Shore University Hospital Manhasset New York United States 11030
    178 NYU Winthrop Hospital Mineola New York United States 11501
    179 NYP/Weill Cornell Medical Center New York New York United States 10065
    180 University of Rochester Rochester New York United States 14642
    181 Randolph Hospital Asheboro North Carolina United States 27203
    182 Wayne Memorial Hospital Goldsboro North Carolina United States 27534
    183 Cone Health Cancer Center Greensboro North Carolina United States 27403
    184 Margaret R Pardee Memorial Hospital Hendersonville North Carolina United States 28791
    185 Vidant Oncology-Kinston Kinston North Carolina United States 28501
    186 FirstHealth of the Carolinas-Moore Regional Hospital Pinehurst North Carolina United States 28374
    187 Annie Penn Memorial Hospital Reidsville North Carolina United States 27320
    188 Iredell Memorial Hospital Statesville North Carolina United States 28677
    189 Southeast Clinical Oncology Research Consortium NCORP Winston-Salem North Carolina United States 27104
    190 Mid Dakota Clinic Bismarck North Dakota United States 58501
    191 Sanford Bismarck Medical Center Bismarck North Dakota United States 58501
    192 Sanford Broadway Medical Center Fargo North Dakota United States 58122
    193 Sanford Clinic North-Fargo Fargo North Dakota United States 58122
    194 Sanford Roger Maris Cancer Center Fargo North Dakota United States 58122
    195 Cleveland Clinic Cancer Center Beachwood Beachwood Ohio United States 44122
    196 University of Cincinnati Cancer Center-UC Medical Center Cincinnati Ohio United States 45219
    197 Case Western Reserve University Cleveland Ohio United States 44106
    198 Cleveland Clinic Cancer Center/Fairview Hospital Cleveland Ohio United States 44111
    199 Cleveland Clinic Foundation Cleveland Ohio United States 44195
    200 Riverside Methodist Hospital Columbus Ohio United States 43214
    201 Columbus NCI Community Oncology Research Program Columbus Ohio United States 43215
    202 The Mark H Zangmeister Center Columbus Ohio United States 43219
    203 Mount Carmel Health Center West Columbus Ohio United States 43222
    204 Miami Valley Hospital Dayton Ohio United States 45409
    205 Cleveland Clinic Cancer Center Independence Independence Ohio United States 44131
    206 Marietta Memorial Hospital Marietta Ohio United States 45750
    207 Hillcrest Hospital Cancer Center Mayfield Heights Ohio United States 44124
    208 Licking Memorial Hospital Newark Ohio United States 43055
    209 University Hospitals Parma Medical Center Parma Ohio United States 44129
    210 North Coast Cancer Care Sandusky Ohio United States 44870
    211 Springfield Regional Medical Center Springfield Ohio United States 45505
    212 Cleveland Clinic Cancer Center Strongsville Strongsville Ohio United States 44136
    213 ProMedica Flower Hospital Sylvania Ohio United States 43560
    214 University of Toledo Toledo Ohio United States 43614
    215 Saint Ann's Hospital Westerville Ohio United States 43081
    216 Cleveland Clinic Wooster Family Health and Surgery Center Wooster Ohio United States 44691
    217 Cancer Care Associates-Norman Norman Oklahoma United States 73071
    218 University of Oklahoma Health Sciences Center Oklahoma City Oklahoma United States 73104
    219 Mercy Hospital Oklahoma City Oklahoma City Oklahoma United States 73120
    220 Legacy Mount Hood Medical Center Gresham Oregon United States 97030
    221 Providence Milwaukie Hospital Milwaukie Oregon United States 97222
    222 Providence Newberg Medical Center Newberg Oregon United States 97132
    223 Providence Willamette Falls Medical Center Oregon City Oregon United States 97045
    224 Legacy Good Samaritan Hospital and Medical Center Portland Oregon United States 97210
    225 Providence Portland Medical Center Portland Oregon United States 97213
    226 Providence Saint Vincent Medical Center Portland Oregon United States 97225
    227 Lehigh Valley Hospital-Cedar Crest Allentown Pennsylvania United States 18103
    228 Carlisle Regional Cancer Center Carlisle Pennsylvania United States 17015
    229 Geisinger Medical Center Danville Pennsylvania United States 17822
    230 Doylestown Hospital Doylestown Pennsylvania United States 18901
    231 Geisinger Medical Center-Cancer Center Hazleton Hazleton Pennsylvania United States 18201
    232 Penn State Milton S Hershey Medical Center Hershey Pennsylvania United States 17033-0850
    233 University of Pittsburgh Cancer Institute (UPCI) Pittsburgh Pennsylvania United States 15232
    234 Guthrie Medical Group PC-Robert Packer Hospital Sayre Pennsylvania United States 18840
    235 Reading Hospital West Reading Pennsylvania United States 19611
    236 Geisinger Wyoming Valley/Henry Cancer Center Wilkes-Barre Pennsylvania United States 18711
    237 Prisma Health Cancer Institute - Spartanburg Boiling Springs South Carolina United States 29316
    238 Roper Hospital Charleston South Carolina United States 29401
    239 Saint Francis Hospital Greenville South Carolina United States 29601
    240 Prisma Health Cancer Institute - Butternut Greenville South Carolina United States 29605
    241 Prisma Health Cancer Institute - Faris Greenville South Carolina United States 29605
    242 Prisma Health Greenville Memorial Hospital Greenville South Carolina United States 29605
    243 Prisma Health Cancer Institute - Eastside Greenville South Carolina United States 29615
    244 Prisma Health Cancer Institute - Seneca Seneca South Carolina United States 29672
    245 Spartanburg Medical Center Spartanburg South Carolina United States 29303
    246 Rapid City Regional Hospital Rapid City South Dakota United States 57701
    247 Sanford Cancer Center Oncology Clinic Sioux Falls South Dakota United States 57104
    248 Sanford USD Medical Center - Sioux Falls Sioux Falls South Dakota United States 57117-5134
    249 Thompson Cancer Survival Center Knoxville Tennessee United States 37916
    250 Vanderbilt University/Ingram Cancer Center Nashville Tennessee United States 37232
    251 The Don and Sybil Harrington Cancer Center Amarillo Texas United States 79106
    252 UT Southwestern/Simmons Cancer Center-Dallas Dallas Texas United States 75390
    253 Huntsman Cancer Institute/University of Utah Salt Lake City Utah United States 84112
    254 Sovah Health Martinsville Martinsville Virginia United States 24115
    255 PeaceHealth Southwest Medical Center Vancouver Washington United States 98664
    256 West Virginia University Healthcare Morgantown West Virginia United States 26506
    257 Marshfield Clinic-Chippewa Center Chippewa Falls Wisconsin United States 54729
    258 HSHS Sacred Heart Hospital Eau Claire Wisconsin United States 54701
    259 Marshfield Clinic Cancer Center at Sacred Heart Eau Claire Wisconsin United States 54701
    260 Green Bay Oncology at Saint Vincent Hospital Green Bay Wisconsin United States 54301-3526
    261 Saint Vincent Hospital Cancer Center Green Bay Green Bay Wisconsin United States 54301
    262 Green Bay Oncology Limited at Saint Mary's Hospital Green Bay Wisconsin United States 54303
    263 Saint Vincent Hospital Cancer Center at Saint Mary's Green Bay Wisconsin United States 54303
    264 Aurora BayCare Medical Center Green Bay Wisconsin United States 54311
    265 Mercyhealth Hospital and Cancer Center - Janesville Janesville Wisconsin United States 53548
    266 Gundersen Lutheran Medical Center La Crosse Wisconsin United States 54601
    267 Dean Hematology and Oncology Clinic Madison Wisconsin United States 53717
    268 Aurora Bay Area Medical Group-Marinette Marinette Wisconsin United States 54143
    269 Bay Area Medical Center Marinette Wisconsin United States 54143
    270 Marshfield Medical Center-Marshfield Marshfield Wisconsin United States 54449
    271 Marshfield Medical Center Marshfield Wisconsin United States 54449
    272 Medical College of Wisconsin Milwaukee Wisconsin United States 53226
    273 Marshfield Clinic-Minocqua Center Minocqua Wisconsin United States 54548
    274 ProHealth Oconomowoc Memorial Hospital Oconomowoc Wisconsin United States 53066
    275 Saint Vincent Hospital Cancer Center at Oconto Falls Oconto Falls Wisconsin United States 54154
    276 Ascension Saint Mary's Hospital Rhinelander Wisconsin United States 54501
    277 Marshfield Medical Center-Rice Lake Rice Lake Wisconsin United States 54868
    278 Ascension Saint Michael's Hospital Stevens Point Wisconsin United States 54481
    279 Green Bay Oncology - Sturgeon Bay Sturgeon Bay Wisconsin United States 54235
    280 Aurora Medical Center in Summit Summit Wisconsin United States 53066
    281 ProHealth Waukesha Memorial Hospital Waukesha Wisconsin United States 53188
    282 Aurora Cancer Care-Milwaukee West Wauwatosa Wisconsin United States 53226
    283 Marshfield Medical Center - Weston Weston Wisconsin United States 54476
    284 Marshfield Clinic - Wisconsin Rapids Center Wisconsin Rapids Wisconsin United States 54494
    285 Tom Baker Cancer Centre Calgary Alberta Canada T2N 4N2
    286 Clinical Research Unit at Vancouver Coastal Health Authority Vancouver British Columbia Canada V5Z 3P1
    287 CancerCare Manitoba Winnipeg Manitoba Canada R3E 0V9
    288 The Moncton Hospital Moncton New Brunswick Canada E1C 6Z8
    289 Atlantic Health Sciences Corporation-Saint John Regional Hospital Saint John New Brunswick Canada E2L 4L2
    290 QEII Health Sciences Centre/Nova Scotia Health Authority Halifax Nova Scotia Canada B3H 2Y9
    291 Juravinski Cancer Centre at Hamilton Health Sciences Hamilton Ontario Canada L8V 5C2
    292 Odette Cancer Centre- Sunnybrook Health Sciences Centre Toronto Ontario Canada M4N 3M5
    293 University Health Network-Princess Margaret Hospital Toronto Ontario Canada M5G 2M9
    294 CSSS Champlain-Charles Le Moyne Greenfield Park Quebec Canada J4V 2H1
    295 McGill University Department of Oncology Montreal Quebec Canada H2W 1S6
    296 The Research Institute of the McGill University Health Centre (MUHC) Montreal Quebec Canada H3H 2R9
    297 Allan Blair Cancer Centre Regina Saskatchewan Canada S4T 7T1
    298 Saskatoon Cancer Centre Saskatoon Saskatchewan Canada S7N 4H4

    Sponsors and Collaborators

    • National Cancer Institute (NCI)

    Investigators

    • Principal Investigator: Mikkael A Sekeres, Southwest Oncology Group

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    National Cancer Institute (NCI)
    ClinicalTrials.gov Identifier:
    NCT01522976
    Other Study ID Numbers:
    • NCI-2012-00242
    • NCI-2012-00242
    • CDR0000723909
    • SWOG-S1117
    • S1117
    • S1117
    • U10CA180888
    • U10CA032102
    First Posted:
    Feb 1, 2012
    Last Update Posted:
    Dec 1, 2021
    Last Verified:
    Nov 1, 2021
    Additional relevant MeSH terms:
    Leukemia
    Preleukemia
    Leukemia, Myelomonocytic, Acute
    Leukemia, Myelomonocytic, Chronic
    Leukemia, Myelomonocytic, Juvenile
    Myelodysplastic Syndromes
    Anemia, Refractory, with Excess of Blasts
    Syndrome
    Lenalidomide
    Azacitidine
    Vorinostat

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title Arm 1: Azacitidine/Lenalidomide Arm 2: Azacitidine Arm 3: Azacitidine/Vorinostat
    Arm/Group Description Patients receive azacitidine SC or IV on days 1-7 or days 1-5 and 8-9, and lenalidomide PO QD on days 1-21. Courses repeat every 28 days for up to 5 years in the absence of disease progression or unacceptable toxicity. Azacitidine: Given SC or IV Lenalidomide: Given PO Patients receive azacitidine as in Arm 1. Courses repeat every 28 days for up to 5 years in the absence of disease progression or unacceptable toxicity. Azacitidine: Given SC or IV Patients receive azacitidine as in Arm 1 and vorinostat PO BID on days 3-9. Courses repeat every 28 days for up to 5 years in the absence of disease progression or unacceptable toxicity. Azacitidine: Given SC or IV Vorinostat: Given PO
    Period Title: Overall Study
    STARTED 97 92 93
    COMPLETED 0 0 0
    NOT COMPLETED 97 92 93

    Baseline Characteristics

    Arm/Group Title Arm 1: Azacitidine/Lenalidomide Arm 2: Azacitidine Arm 3: Azacitidine/Vorinostat Total
    Arm/Group Description Patients receive azacitidine SC or IV on days 1-7 or days 1-5 and 8-9, and lenalidomide PO QD on days 1-21. Courses repeat every 28 days for up to 5 years in the absence of disease progression or unacceptable toxicity. Azacitidine: Given SC or IV Lenalidomide: Given PO Patients receive azacitidine as in Arm 1. Courses repeat every 28 days for up to 5 years in the absence of disease progression or unacceptable toxicity. Azacitidine: Given SC or IV Patients receive azacitidine as in Arm 1 and vorinostat PO BID on days 3-9. Courses repeat every 28 days for up to 5 years in the absence of disease progression or unacceptable toxicity. Azacitidine: Given SC or IV Vorinostat: Given PO Total of all reporting groups
    Overall Participants 93 92 92 277
    Age (years) [Median (Full Range) ]
    Median (Full Range) [years]
    70.81
    69.67
    70.36
    70.18
    Sex: Female, Male (Count of Participants)
    Female
    32
    34.4%
    31
    33.7%
    22
    23.9%
    85
    30.7%
    Male
    61
    65.6%
    61
    66.3%
    70
    76.1%
    192
    69.3%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    1
    1.1%
    0
    0%
    1
    1.1%
    2
    0.7%
    Asian
    1
    1.1%
    4
    4.3%
    2
    2.2%
    7
    2.5%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    1
    1.1%
    1
    0.4%
    Black or African American
    2
    2.2%
    3
    3.3%
    4
    4.3%
    9
    3.2%
    White
    86
    92.5%
    80
    87%
    83
    90.2%
    249
    89.9%
    More than one race
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Unknown or Not Reported
    3
    3.2%
    5
    5.4%
    1
    1.1%
    9
    3.2%

    Outcome Measures

    1. Primary Outcome
    Title Response Rate (Phase II)
    Description A response is any of complete hematological remission, partial remission, or hematologic improvement.
    Time Frame Up to 5 years

    Outcome Measure Data

    Analysis Population Description
    Analysis includes eligible patients only.
    Arm/Group Title Arm 1: Azacitidine/Lenalidomide Arm 2: Azacitidine Arm 3: Azacitidine/Vorinostat
    Arm/Group Description Patients receive azacitidine SC or IV on days 1-7 or days 1-5 and 8-9, and lenalidomide PO QD on days 1-21. Courses repeat every 28 days for up to 5 years in the absence of disease progression or unacceptable toxicity. Azacitidine: Given SC or IV Lenalidomide: Given PO Patients receive azacitidine as in Arm 1. Courses repeat every 28 days for up to 5 years in the absence of disease progression or unacceptable toxicity. Azacitidine: Given SC or IV Patients receive azacitidine as in Arm 1 and vorinostat PO BID on days 3-9. Courses repeat every 28 days for up to 5 years in the absence of disease progression or unacceptable toxicity. Azacitidine: Given SC or IV Vorinostat: Given PO
    Measure Participants 93 92 92
    Number (95% Confidence Interval) [percentage of patients having a response]
    49
    38
    27
    2. Primary Outcome
    Title Overall Survival (Phase III)
    Description OS is calculated for all patients from the date of initial registration to date of death due to any cause. The follow-up for patients last known to be alive is censored at the date of last contact. Stratified Cox regression models will be used to compare OS of the combination arm selected in the Phase II portion of the trial to OS of the single-agent azacitidine arm.
    Time Frame Up to 5 years

    Outcome Measure Data

    Analysis Population Description
    This trial did not proceed to the Phase III portion. Therefore, no patients were analyzed for this outcome measure.
    Arm/Group Title Arm 1: Azacitidine/Lenalidomide Arm 2: Azacitidine Arm 3: Azacitidine/Vorinostat
    Arm/Group Description Patients receive azacitidine SC or IV on days 1-7 or days 1-5 and 8-9, and lenalidomide PO QD on days 1-21. Courses repeat every 28 days for up to 5 years in the absence of disease progression or unacceptable toxicity. Azacitidine: Given SC or IV Lenalidomide: Given PO Patients receive azacitidine as in Arm 1. Courses repeat every 28 days for up to 5 years in the absence of disease progression or unacceptable toxicity. Azacitidine: Given SC or IV Patients receive azacitidine as in Arm 1 and vorinostat PO BID on days 3-9. Courses repeat every 28 days for up to 5 years in the absence of disease progression or unacceptable toxicity. Azacitidine: Given SC or IV Vorinostat: Given PO
    Measure Participants 0 0 0
    3. Secondary Outcome
    Title Relapse-free Survival
    Description RFS is calculated for patients who have achieved a response. RFS will be measured from the date of response to the date of first documentation of relapse from response (as defined in the primary objective), or death due to any cause. The follow-up for patients last known to be alive and without report of relapse is censored at the date of last contact. RFS will be estimated for each of the three arms using the Kaplan-Meier method.
    Time Frame Up to 5 years

    Outcome Measure Data

    Analysis Population Description
    Analysis includes eligible patients who had a response.
    Arm/Group Title Arm 1: Azacitidine/Lenalidomide Arm 2: Azacitidine Arm 3: Azacitidine/Vorinostat
    Arm/Group Description Patients receive azacitidine SC or IV on days 1-7 or days 1-5 and 8-9, and lenalidomide PO QD on days 1-21. Courses repeat every 28 days for up to 5 years in the absence of disease progression or unacceptable toxicity. Azacitidine: Given SC or IV Lenalidomide: Given PO Patients receive azacitidine as in Arm 1. Courses repeat every 28 days for up to 5 years in the absence of disease progression or unacceptable toxicity. Azacitidine: Given SC or IV Patients receive azacitidine as in Arm 1 and vorinostat PO BID on days 3-9. Courses repeat every 28 days for up to 5 years in the absence of disease progression or unacceptable toxicity. Azacitidine: Given SC or IV Vorinostat: Given PO
    Measure Participants 46 35 25
    Median (95% Confidence Interval) [Days]
    435
    311
    455
    4. Secondary Outcome
    Title Overall Survival
    Description OS is calculated for all patients from the date of initial registration to date of death due to any cause. The follow- up for patients last known to be alive is censored at the date of last contact. OS will be estimated for each of the three arms using the Kaplan-Meier method.
    Time Frame Up to 5 years

    Outcome Measure Data

    Analysis Population Description
    Analysis includes eligible patients only.
    Arm/Group Title Arm 1: Azacitidine/Lenalidomide Arm 2: Azacitidine Arm 3: Azacitidine/Vorinostat
    Arm/Group Description Patients receive azacitidine SC or IV on days 1-7 or days 1-5 and 8-9, and lenalidomide PO QD on days 1-21. Courses repeat every 28 days for up to 5 years in the absence of disease progression or unacceptable toxicity. Azacitidine: Given SC or IV Lenalidomide: Given PO Patients receive azacitidine as in Arm 1. Courses repeat every 28 days for up to 5 years in the absence of disease progression or unacceptable toxicity. Azacitidine: Given SC or IV Patients receive azacitidine as in Arm 1 and vorinostat PO BID on days 3-9. Courses repeat every 28 days for up to 5 years in the absence of disease progression or unacceptable toxicity. Azacitidine: Given SC or IV Vorinostat: Given PO
    Measure Participants 93 92 92
    Median (95% Confidence Interval) [Days]
    588
    449
    527
    5. Secondary Outcome
    Title Pre-study Cytogenetic Abnormalities
    Description Cytogenetic risk group is used to identify cytogenetic abnormalities.
    Time Frame Up to 5 years

    Outcome Measure Data

    Analysis Population Description
    Analysis includes eligible patients only.
    Arm/Group Title Arm 1: Azacitidine/Lenalidomide Arm 2: Azacitidine Arm 3: Azacitidine/Vorinostat
    Arm/Group Description Patients receive azacitidine SC or IV on days 1-7 or days 1-5 and 8-9, and lenalidomide PO QD on days 1-21. Courses repeat every 28 days for up to 5 years in the absence of disease progression or unacceptable toxicity. Azacitidine: Given SC or IV Lenalidomide: Given PO Patients receive azacitidine as in Arm 1. Courses repeat every 28 days for up to 5 years in the absence of disease progression or unacceptable toxicity. Azacitidine: Given SC or IV Patients receive azacitidine as in Arm 1 and vorinostat PO BID on days 3-9. Courses repeat every 28 days for up to 5 years in the absence of disease progression or unacceptable toxicity. Azacitidine: Given SC or IV Vorinostat: Given PO
    Measure Participants 93 92 92
    Good/very good
    35
    37.6%
    29
    31.5%
    34
    37%
    Intermediate
    13
    14%
    16
    17.4%
    18
    19.6%
    Poor
    8
    8.6%
    10
    10.9%
    8
    8.7%
    Very poor
    23
    24.7%
    23
    25%
    19
    20.7%
    Missing
    14
    15.1%
    14
    15.2%
    13
    14.1%
    6. Secondary Outcome
    Title Toxicity Rate
    Description Adverse events that are possibly, probably or definitely related to study drug are reported.
    Time Frame Up to 5 years

    Outcome Measure Data

    Analysis Population Description
    Analysis includes only eligible patients who also received treatment.
    Arm/Group Title Arm 1: Azacitidine/Lenalidomide Arm 2: Azacitidine Arm 3: Azacitidine/Vorinostat
    Arm/Group Description Patients receive azacitidine SC or IV on days 1-7 or days 1-5 and 8-9, and lenalidomide PO QD on days 1-21. Courses repeat every 28 days for up to 5 years in the absence of disease progression or unacceptable toxicity. Azacitidine: Given SC or IV Patients receive azacitidine as in Arm 1. Courses repeat every 28 days for up to 5 years in the absence of disease progression or unacceptable toxicity. Azacitidine: Given SC or IV Patients receive azacitidine as in Arm 1 and vorinostat PO BID on days 3-9. Courses repeat every 28 days for up to 5 years in the absence of disease progression or unacceptable toxicity. Azacitidine: Given SC or IV Vorinostat: Given PO
    Measure Participants 89 91 91
    Abdominal infection
    1
    1.1%
    0
    0%
    0
    0%
    Abdominal pain
    1
    1.1%
    0
    0%
    3
    3.3%
    Acute kidney injury
    0
    0%
    0
    0%
    1
    1.1%
    Adult respiratory distress syndrome
    1
    1.1%
    0
    0%
    0
    0%
    Alanine aminotransferase increased
    0
    0%
    0
    0%
    5
    5.4%
    Anemia
    48
    51.6%
    37
    40.2%
    44
    47.8%
    Anorectal infection
    0
    0%
    0
    0%
    1
    1.1%
    Anorexia
    4
    4.3%
    0
    0%
    3
    3.3%
    Apnea
    0
    0%
    0
    0%
    1
    1.1%
    Ascites
    1
    1.1%
    0
    0%
    1
    1.1%
    Aspartate aminotransferase increased
    0
    0%
    0
    0%
    3
    3.3%
    Ataxia
    0
    0%
    0
    0%
    1
    1.1%
    Back pain
    1
    1.1%
    0
    0%
    0
    0%
    Blood and lymphatic system disorders - Other
    0
    0%
    2
    2.2%
    1
    1.1%
    Blood bilirubin increased
    0
    0%
    0
    0%
    3
    3.3%
    Bronchial infection
    0
    0%
    0
    0%
    1
    1.1%
    CD4 lymphocytes decreased
    1
    1.1%
    0
    0%
    0
    0%
    Cardiac arrest
    1
    1.1%
    0
    0%
    0
    0%
    Catheter related infection
    1
    1.1%
    2
    2.2%
    1
    1.1%
    Cecal infection
    0
    0%
    0
    0%
    1
    1.1%
    Cholecystitis
    0
    0%
    0
    0%
    1
    1.1%
    Colitis
    0
    0%
    0
    0%
    1
    1.1%
    Confusion
    0
    0%
    0
    0%
    1
    1.1%
    Constipation
    2
    2.2%
    1
    1.1%
    1
    1.1%
    Creatinine increased
    2
    2.2%
    0
    0%
    0
    0%
    Dehydration
    5
    5.4%
    1
    1.1%
    3
    3.3%
    Delirium
    0
    0%
    0
    0%
    1
    1.1%
    Diarrhea
    5
    5.4%
    0
    0%
    3
    3.3%
    Dizziness
    1
    1.1%
    0
    0%
    0
    0%
    Dyspnea
    4
    4.3%
    2
    2.2%
    3
    3.3%
    Epistaxis
    0
    0%
    0
    0%
    1
    1.1%
    Esophageal pain
    0
    0%
    0
    0%
    1
    1.1%
    Esophagitis
    1
    1.1%
    0
    0%
    0
    0%
    Fall
    0
    0%
    0
    0%
    1
    1.1%
    Fatigue
    9
    9.7%
    6
    6.5%
    14
    15.2%
    Febrile neutropenia
    16
    17.2%
    11
    12%
    13
    14.1%
    Fever
    0
    0%
    0
    0%
    2
    2.2%
    Flushing
    0
    0%
    0
    0%
    1
    1.1%
    Gastric hemorrhage
    0
    0%
    0
    0%
    1
    1.1%
    Gastrointestinal pain
    1
    1.1%
    0
    0%
    1
    1.1%
    General disorders and admin site conditions-Other
    1
    1.1%
    0
    0%
    0
    0%
    Generalized muscle weakness
    3
    3.2%
    1
    1.1%
    3
    3.3%
    Hallucinations
    0
    0%
    0
    0%
    1
    1.1%
    Headache
    0
    0%
    0
    0%
    1
    1.1%
    Heart failure
    0
    0%
    0
    0%
    1
    1.1%
    Hematoma
    0
    0%
    0
    0%
    1
    1.1%
    Hematuria
    1
    1.1%
    0
    0%
    2
    2.2%
    Hyperglycemia
    1
    1.1%
    1
    1.1%
    2
    2.2%
    Hypernatremia
    0
    0%
    1
    1.1%
    0
    0%
    Hypertension
    1
    1.1%
    0
    0%
    2
    2.2%
    Hyperuricemia
    0
    0%
    0
    0%
    1
    1.1%
    Hypoalbuminemia
    3
    3.2%
    0
    0%
    0
    0%
    Hypokalemia
    4
    4.3%
    0
    0%
    1
    1.1%
    Hypomagnesemia
    1
    1.1%
    0
    0%
    0
    0%
    Hyponatremia
    5
    5.4%
    1
    1.1%
    4
    4.3%
    Hypophosphatemia
    1
    1.1%
    0
    0%
    2
    2.2%
    Hypotension
    4
    4.3%
    0
    0%
    3
    3.3%
    Hypoxia
    0
    0%
    0
    0%
    1
    1.1%
    Infections and infestations - Other, specify
    4
    4.3%
    2
    2.2%
    5
    5.4%
    Intracranial hemorrhage
    1
    1.1%
    0
    0%
    0
    0%
    Investigations - Other, specify
    1
    1.1%
    0
    0%
    0
    0%
    Leukocytosis
    0
    0%
    1
    1.1%
    0
    0%
    Lower gastrointestinal hemorrhage
    0
    0%
    0
    0%
    2
    2.2%
    Lung infection
    4
    4.3%
    1
    1.1%
    2
    2.2%
    Lymphocyte count decreased
    14
    15.1%
    9
    9.8%
    3
    3.3%
    Lymphocyte count increased
    0
    0%
    1
    1.1%
    1
    1.1%
    Mucosal infection
    0
    0%
    0
    0%
    1
    1.1%
    Mucositis oral
    1
    1.1%
    0
    0%
    0
    0%
    Nausea
    1
    1.1%
    2
    2.2%
    2
    2.2%
    Neutrophil count decreased
    69
    74.2%
    48
    52.2%
    63
    68.5%
    Pain
    1
    1.1%
    0
    0%
    0
    0%
    Papulopustular rash
    1
    1.1%
    0
    0%
    0
    0%
    Pericardial effusion
    1
    1.1%
    0
    0%
    0
    0%
    Platelet count decreased
    61
    65.6%
    46
    50%
    64
    69.6%
    Pneumonitis
    0
    0%
    0
    0%
    1
    1.1%
    Pruritus
    1
    1.1%
    0
    0%
    0
    0%
    Pulmonary edema
    0
    0%
    0
    0%
    1
    1.1%
    Purpura
    1
    1.1%
    0
    0%
    0
    0%
    Rash maculo-papular
    13
    14%
    3
    3.3%
    1
    1.1%
    Renal and urinary disorders - Other, specify
    0
    0%
    0
    0%
    1
    1.1%
    Respiratory failure
    0
    0%
    0
    0%
    1
    1.1%
    Sepsis
    4
    4.3%
    2
    2.2%
    3
    3.3%
    Sinus bradycardia
    1
    1.1%
    0
    0%
    0
    0%
    Skin infection
    3
    3.2%
    1
    1.1%
    2
    2.2%
    Soft tissue infection
    1
    1.1%
    1
    1.1%
    0
    0%
    Sudden death NOS
    0
    0%
    1
    1.1%
    0
    0%
    Syncope
    2
    2.2%
    0
    0%
    4
    4.3%
    Thromboembolic event
    1
    1.1%
    0
    0%
    1
    1.1%
    Tooth infection
    0
    0%
    0
    0%
    1
    1.1%
    Upper gastrointestinal hemorrhage
    0
    0%
    0
    0%
    1
    1.1%
    Upper respiratory infection
    0
    0%
    1
    1.1%
    0
    0%
    Urinary tract infection
    1
    1.1%
    1
    1.1%
    1
    1.1%
    Vascular disorders - Other, specify
    0
    0%
    0
    0%
    1
    1.1%
    Vomiting
    1
    1.1%
    1
    1.1%
    1
    1.1%
    Weight loss
    1
    1.1%
    0
    0%
    0
    0%
    White blood cell decreased
    48
    51.6%
    34
    37%
    44
    47.8%

    Adverse Events

    Time Frame Up to 5 years
    Adverse Event Reporting Description Analysis includes only eligible patients who also received treatment. Adverse events that are possibly, probably or definitely related to study drug are reported.
    Arm/Group Title Arm 1: Azacitidine/Lenalidomide Arm 2: Azacitidine Arm 3: Azacitidine/Vorinostat
    Arm/Group Description Patients receive azacitidine SC or IV on days 1-7 or days 1-5 and 8-9, and lenalidomide PO QD on days 1-21. Courses repeat every 28 days for up to 5 years in the absence of disease progression or unacceptable toxicity. Azacitidine: Given SC or IV Lenalidomide: Given PO Patients receive azacitidine as in Arm 1. Courses repeat every 28 days for up to 5 years in the absence of disease progression or unacceptable toxicity. Azacitidine: Given SC or IV Patients receive azacitidine as in Arm 1 and vorinostat PO BID on days 3-9. Courses repeat every 28 days for up to 5 years in the absence of disease progression or unacceptable toxicity. Azacitidine: Given SC or IV Vorinostat: Given PO
    All Cause Mortality
    Arm 1: Azacitidine/Lenalidomide Arm 2: Azacitidine Arm 3: Azacitidine/Vorinostat
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN) / (NaN)
    Serious Adverse Events
    Arm 1: Azacitidine/Lenalidomide Arm 2: Azacitidine Arm 3: Azacitidine/Vorinostat
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 37/89 (41.6%) 8/91 (8.8%) 47/91 (51.6%)
    Blood and lymphatic system disorders
    Anemia 6/89 (6.7%) 0/91 (0%) 6/91 (6.6%)
    Blood and lymphatic system disorders - Other 0/89 (0%) 0/91 (0%) 1/91 (1.1%)
    Febrile neutropenia 6/89 (6.7%) 1/91 (1.1%) 2/91 (2.2%)
    Cardiac disorders
    Atrial fibrillation 4/89 (4.5%) 0/91 (0%) 0/91 (0%)
    Atrioventricular block first degree 0/89 (0%) 0/91 (0%) 1/91 (1.1%)
    Cardiac arrest 1/89 (1.1%) 1/91 (1.1%) 0/91 (0%)
    Chest pain - cardiac 0/89 (0%) 0/91 (0%) 2/91 (2.2%)
    Heart failure 1/89 (1.1%) 0/91 (0%) 2/91 (2.2%)
    Myocardial infarction 1/89 (1.1%) 0/91 (0%) 0/91 (0%)
    Pericardial effusion 1/89 (1.1%) 0/91 (0%) 1/91 (1.1%)
    Sinus bradycardia 2/89 (2.2%) 0/91 (0%) 2/91 (2.2%)
    Sinus tachycardia 0/89 (0%) 0/91 (0%) 1/91 (1.1%)
    Ventricular arrhythmia 1/89 (1.1%) 0/91 (0%) 0/91 (0%)
    Ventricular tachycardia 1/89 (1.1%) 0/91 (0%) 0/91 (0%)
    Endocrine disorders
    Adrenal insufficiency 1/89 (1.1%) 0/91 (0%) 0/91 (0%)
    Gastrointestinal disorders
    Abdominal pain 0/89 (0%) 0/91 (0%) 5/91 (5.5%)
    Ascites 1/89 (1.1%) 0/91 (0%) 1/91 (1.1%)
    Colitis 0/89 (0%) 0/91 (0%) 2/91 (2.2%)
    Constipation 1/89 (1.1%) 0/91 (0%) 2/91 (2.2%)
    Dental caries 0/89 (0%) 0/91 (0%) 1/91 (1.1%)
    Dysphagia 0/89 (0%) 0/91 (0%) 1/91 (1.1%)
    Enterocolitis 0/89 (0%) 0/91 (0%) 2/91 (2.2%)
    Esophageal pain 0/89 (0%) 0/91 (0%) 1/91 (1.1%)
    Gastric hemorrhage 0/89 (0%) 0/91 (0%) 1/91 (1.1%)
    Gastrointestinal disorders-Other 0/89 (0%) 0/91 (0%) 2/91 (2.2%)
    Gastrointestinal pain 0/89 (0%) 0/91 (0%) 1/91 (1.1%)
    Ileus 1/89 (1.1%) 0/91 (0%) 0/91 (0%)
    Jejunal hemorrhage 0/89 (0%) 0/91 (0%) 1/91 (1.1%)
    Lower gastrointestinal hemorrhage 0/89 (0%) 0/91 (0%) 1/91 (1.1%)
    Mucositis oral 1/89 (1.1%) 0/91 (0%) 0/91 (0%)
    Nausea 1/89 (1.1%) 0/91 (0%) 2/91 (2.2%)
    Small intestinal obstruction 0/89 (0%) 0/91 (0%) 1/91 (1.1%)
    Upper gastrointestinal hemorrhage 0/89 (0%) 0/91 (0%) 2/91 (2.2%)
    Vomiting 0/89 (0%) 0/91 (0%) 1/91 (1.1%)
    General disorders
    Death NOS 0/89 (0%) 1/91 (1.1%) 0/91 (0%)
    Edema limbs 0/89 (0%) 0/91 (0%) 2/91 (2.2%)
    Fatigue 1/89 (1.1%) 0/91 (0%) 4/91 (4.4%)
    Fever 1/89 (1.1%) 0/91 (0%) 6/91 (6.6%)
    Infusion related reaction 1/89 (1.1%) 0/91 (0%) 0/91 (0%)
    Malaise 1/89 (1.1%) 0/91 (0%) 0/91 (0%)
    Non-cardiac chest pain 1/89 (1.1%) 0/91 (0%) 1/91 (1.1%)
    Pain 1/89 (1.1%) 0/91 (0%) 0/91 (0%)
    Sudden death NOS 0/89 (0%) 1/91 (1.1%) 0/91 (0%)
    Hepatobiliary disorders
    Cholecystitis 0/89 (0%) 0/91 (0%) 2/91 (2.2%)
    Hepatobiliary disorders-Other 2/89 (2.2%) 0/91 (0%) 0/91 (0%)
    Immune system disorders
    Allergic reaction 1/89 (1.1%) 0/91 (0%) 1/91 (1.1%)
    Infections and infestations
    Abdominal infection 1/89 (1.1%) 0/91 (0%) 0/91 (0%)
    Anorectal infection 0/89 (0%) 0/91 (0%) 1/91 (1.1%)
    Bronchial infection 0/89 (0%) 0/91 (0%) 1/91 (1.1%)
    Catheter related infection 0/89 (0%) 0/91 (0%) 1/91 (1.1%)
    Infections and infestations-Other 4/89 (4.5%) 0/91 (0%) 8/91 (8.8%)
    Lip infection 1/89 (1.1%) 0/91 (0%) 0/91 (0%)
    Lung infection 5/89 (5.6%) 0/91 (0%) 4/91 (4.4%)
    Mucosal infection 0/89 (0%) 0/91 (0%) 1/91 (1.1%)
    Sepsis 4/89 (4.5%) 2/91 (2.2%) 4/91 (4.4%)
    Skin infection 2/89 (2.2%) 0/91 (0%) 1/91 (1.1%)
    Soft tissue infection 1/89 (1.1%) 0/91 (0%) 0/91 (0%)
    Tooth infection 0/89 (0%) 0/91 (0%) 1/91 (1.1%)
    Urinary tract infection 0/89 (0%) 1/91 (1.1%) 3/91 (3.3%)
    Injury, poisoning and procedural complications
    Fracture 1/89 (1.1%) 0/91 (0%) 1/91 (1.1%)
    Investigations
    Alanine aminotransferase increased 0/89 (0%) 0/91 (0%) 2/91 (2.2%)
    Aspartate aminotransferase increased 0/89 (0%) 0/91 (0%) 2/91 (2.2%)
    Blood bilirubin increased 1/89 (1.1%) 0/91 (0%) 1/91 (1.1%)
    Cardiac troponin I increased 1/89 (1.1%) 0/91 (0%) 0/91 (0%)
    Creatinine increased 2/89 (2.2%) 0/91 (0%) 2/91 (2.2%)
    Investigations-Other 1/89 (1.1%) 0/91 (0%) 0/91 (0%)
    Lymphocyte count increased 0/89 (0%) 0/91 (0%) 1/91 (1.1%)
    Neutrophil count decreased 2/89 (2.2%) 0/91 (0%) 4/91 (4.4%)
    Platelet count decreased 7/89 (7.9%) 0/91 (0%) 8/91 (8.8%)
    White blood cell decreased 3/89 (3.4%) 0/91 (0%) 2/91 (2.2%)
    Metabolism and nutrition disorders
    Anorexia 1/89 (1.1%) 0/91 (0%) 1/91 (1.1%)
    Dehydration 3/89 (3.4%) 0/91 (0%) 2/91 (2.2%)
    Hyperglycemia 2/89 (2.2%) 0/91 (0%) 2/91 (2.2%)
    Hypoalbuminemia 2/89 (2.2%) 0/91 (0%) 0/91 (0%)
    Hypocalcemia 2/89 (2.2%) 0/91 (0%) 0/91 (0%)
    Hypokalemia 4/89 (4.5%) 0/91 (0%) 0/91 (0%)
    Hypomagnesemia 1/89 (1.1%) 0/91 (0%) 0/91 (0%)
    Hyponatremia 4/89 (4.5%) 0/91 (0%) 2/91 (2.2%)
    Hypophosphatemia 0/89 (0%) 0/91 (0%) 2/91 (2.2%)
    Metabolism and nutrition disorders - Other, specify 1/89 (1.1%) 0/91 (0%) 0/91 (0%)
    Musculoskeletal and connective tissue disorders
    Back pain 0/89 (0%) 0/91 (0%) 2/91 (2.2%)
    Generalized muscle weakness 2/89 (2.2%) 0/91 (0%) 3/91 (3.3%)
    Neck pain 1/89 (1.1%) 0/91 (0%) 0/91 (0%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Neoplasms benign, malignant and unspecified - Other 2/89 (2.2%) 0/91 (0%) 0/91 (0%)
    Nervous system disorders
    Dizziness 2/89 (2.2%) 0/91 (0%) 1/91 (1.1%)
    Headache 1/89 (1.1%) 0/91 (0%) 0/91 (0%)
    Intracranial hemorrhage 2/89 (2.2%) 1/91 (1.1%) 0/91 (0%)
    Nervous system disorders-Other 0/89 (0%) 1/91 (1.1%) 0/91 (0%)
    Presyncope 1/89 (1.1%) 0/91 (0%) 1/91 (1.1%)
    Stroke 1/89 (1.1%) 0/91 (0%) 1/91 (1.1%)
    Syncope 1/89 (1.1%) 0/91 (0%) 4/91 (4.4%)
    Psychiatric disorders
    Confusion 1/89 (1.1%) 0/91 (0%) 0/91 (0%)
    Delirium 0/89 (0%) 0/91 (0%) 1/91 (1.1%)
    Hallucinations 0/89 (0%) 0/91 (0%) 1/91 (1.1%)
    Renal and urinary disorders
    Acute kidney injury 2/89 (2.2%) 0/91 (0%) 1/91 (1.1%)
    Chronic kidney disease 0/89 (0%) 0/91 (0%) 1/91 (1.1%)
    Hematuria 1/89 (1.1%) 0/91 (0%) 2/91 (2.2%)
    Renal and urinary disorders-Other 0/89 (0%) 0/91 (0%) 1/91 (1.1%)
    Renal calculi 1/89 (1.1%) 0/91 (0%) 0/91 (0%)
    Respiratory, thoracic and mediastinal disorders
    Adult respiratory distress syndrome 1/89 (1.1%) 0/91 (0%) 0/91 (0%)
    Cough 0/89 (0%) 0/91 (0%) 1/91 (1.1%)
    Dyspnea 6/89 (6.7%) 0/91 (0%) 2/91 (2.2%)
    Epistaxis 0/89 (0%) 0/91 (0%) 1/91 (1.1%)
    Hypoxia 1/89 (1.1%) 0/91 (0%) 1/91 (1.1%)
    Laryngeal hemorrhage 0/89 (0%) 0/91 (0%) 1/91 (1.1%)
    Pleural effusion 0/89 (0%) 0/91 (0%) 2/91 (2.2%)
    Pneumonitis 1/89 (1.1%) 0/91 (0%) 1/91 (1.1%)
    Pulmonary edema 0/89 (0%) 0/91 (0%) 1/91 (1.1%)
    Resp, thoracic and mediastinal disorders - Other 1/89 (1.1%) 0/91 (0%) 0/91 (0%)
    Respiratory failure 1/89 (1.1%) 0/91 (0%) 2/91 (2.2%)
    Skin and subcutaneous tissue disorders
    Rash maculo-papular 4/89 (4.5%) 0/91 (0%) 0/91 (0%)
    Skin and subcutaneous tissue disorders - Other 0/89 (0%) 0/91 (0%) 1/91 (1.1%)
    Vascular disorders
    Flushing 0/89 (0%) 0/91 (0%) 1/91 (1.1%)
    Hematoma 0/89 (0%) 0/91 (0%) 1/91 (1.1%)
    Hypertension 2/89 (2.2%) 0/91 (0%) 2/91 (2.2%)
    Hypotension 3/89 (3.4%) 0/91 (0%) 3/91 (3.3%)
    Thromboembolic event 1/89 (1.1%) 0/91 (0%) 1/91 (1.1%)
    Vascular disorders-Other 0/89 (0%) 0/91 (0%) 1/91 (1.1%)
    Other (Not Including Serious) Adverse Events
    Arm 1: Azacitidine/Lenalidomide Arm 2: Azacitidine Arm 3: Azacitidine/Vorinostat
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 88/89 (98.9%) 89/91 (97.8%) 91/91 (100%)
    Blood and lymphatic system disorders
    Anemia 76/89 (85.4%) 71/91 (78%) 72/91 (79.1%)
    Febrile neutropenia 13/89 (14.6%) 14/91 (15.4%) 13/91 (14.3%)
    Cardiac disorders
    Chest pain - cardiac 3/89 (3.4%) 2/91 (2.2%) 6/91 (6.6%)
    Sinus tachycardia 3/89 (3.4%) 4/91 (4.4%) 9/91 (9.9%)
    Gastrointestinal disorders
    Abdominal pain 8/89 (9%) 14/91 (15.4%) 21/91 (23.1%)
    Constipation 49/89 (55.1%) 54/91 (59.3%) 44/91 (48.4%)
    Diarrhea 42/89 (47.2%) 23/91 (25.3%) 53/91 (58.2%)
    Dry mouth 10/89 (11.2%) 9/91 (9.9%) 7/91 (7.7%)
    Dyspepsia 4/89 (4.5%) 13/91 (14.3%) 7/91 (7.7%)
    Gastroesophageal reflux disease 4/89 (4.5%) 1/91 (1.1%) 6/91 (6.6%)
    Hemorrhoids 5/89 (5.6%) 2/91 (2.2%) 4/91 (4.4%)
    Mucositis oral 15/89 (16.9%) 7/91 (7.7%) 10/91 (11%)
    Nausea 38/89 (42.7%) 42/91 (46.2%) 61/91 (67%)
    Oral pain 5/89 (5.6%) 2/91 (2.2%) 4/91 (4.4%)
    Vomiting 18/89 (20.2%) 18/91 (19.8%) 36/91 (39.6%)
    General disorders
    Chills 19/89 (21.3%) 11/91 (12.1%) 10/91 (11%)
    Edema limbs 24/89 (27%) 22/91 (24.2%) 28/91 (30.8%)
    Fatigue 74/89 (83.1%) 69/91 (75.8%) 74/91 (81.3%)
    Fever 14/89 (15.7%) 19/91 (20.9%) 15/91 (16.5%)
    General disorders and admin site conditions - Other 5/89 (5.6%) 4/91 (4.4%) 5/91 (5.5%)
    Injection site reaction 22/89 (24.7%) 19/91 (20.9%) 18/91 (19.8%)
    Non-cardiac chest pain 2/89 (2.2%) 3/91 (3.3%) 5/91 (5.5%)
    Pain 14/89 (15.7%) 10/91 (11%) 10/91 (11%)
    Infections and infestations
    Infections and infestations-Other 9/89 (10.1%) 10/91 (11%) 8/91 (8.8%)
    Lung infection 2/89 (2.2%) 6/91 (6.6%) 5/91 (5.5%)
    Skin infection 9/89 (10.1%) 13/91 (14.3%) 9/91 (9.9%)
    Upper respiratory infection 5/89 (5.6%) 6/91 (6.6%) 4/91 (4.4%)
    Urinary tract infection 8/89 (9%) 2/91 (2.2%) 3/91 (3.3%)
    Injury, poisoning and procedural complications
    Bruising 25/89 (28.1%) 24/91 (26.4%) 18/91 (19.8%)
    Fall 0/89 (0%) 6/91 (6.6%) 7/91 (7.7%)
    Injury, poison and procedural complications - Other 2/89 (2.2%) 5/91 (5.5%) 0/91 (0%)
    Investigations
    Alanine aminotransferase increased 18/89 (20.2%) 16/91 (17.6%) 17/91 (18.7%)
    Alkaline phosphatase increased 17/89 (19.1%) 16/91 (17.6%) 13/91 (14.3%)
    Aspartate aminotransferase increased 18/89 (20.2%) 23/91 (25.3%) 17/91 (18.7%)
    Blood bilirubin increased 14/89 (15.7%) 13/91 (14.3%) 24/91 (26.4%)
    Creatinine increased 21/89 (23.6%) 26/91 (28.6%) 25/91 (27.5%)
    INR increased 4/89 (4.5%) 5/91 (5.5%) 3/91 (3.3%)
    Lymphocyte count decreased 32/89 (36%) 16/91 (17.6%) 19/91 (20.9%)
    Neutrophil count decreased 77/89 (86.5%) 58/91 (63.7%) 73/91 (80.2%)
    Platelet count decreased 78/89 (87.6%) 68/91 (74.7%) 69/91 (75.8%)
    Weight loss 22/89 (24.7%) 15/91 (16.5%) 19/91 (20.9%)
    White blood cell decreased 66/89 (74.2%) 52/91 (57.1%) 60/91 (65.9%)
    Metabolism and nutrition disorders
    Anorexia 39/89 (43.8%) 31/91 (34.1%) 45/91 (49.5%)
    Dehydration 9/89 (10.1%) 10/91 (11%) 17/91 (18.7%)
    Hypercalcemia 2/89 (2.2%) 6/91 (6.6%) 3/91 (3.3%)
    Hyperglycemia 33/89 (37.1%) 27/91 (29.7%) 32/91 (35.2%)
    Hyperkalemia 6/89 (6.7%) 6/91 (6.6%) 6/91 (6.6%)
    Hypermagnesemia 3/89 (3.4%) 7/91 (7.7%) 5/91 (5.5%)
    Hypernatremia 5/89 (5.6%) 3/91 (3.3%) 3/91 (3.3%)
    Hyperuricemia 2/89 (2.2%) 5/91 (5.5%) 3/91 (3.3%)
    Hypoalbuminemia 29/89 (32.6%) 21/91 (23.1%) 32/91 (35.2%)
    Hypocalcemia 30/89 (33.7%) 16/91 (17.6%) 25/91 (27.5%)
    Hypokalemia 40/89 (44.9%) 15/91 (16.5%) 19/91 (20.9%)
    Hypomagnesemia 13/89 (14.6%) 10/91 (11%) 9/91 (9.9%)
    Hyponatremia 23/89 (25.8%) 22/91 (24.2%) 34/91 (37.4%)
    Hypophosphatemia 4/89 (4.5%) 2/91 (2.2%) 6/91 (6.6%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 15/89 (16.9%) 11/91 (12.1%) 7/91 (7.7%)
    Back pain 16/89 (18%) 18/91 (19.8%) 14/91 (15.4%)
    Bone pain 6/89 (6.7%) 2/91 (2.2%) 3/91 (3.3%)
    Generalized muscle weakness 22/89 (24.7%) 15/91 (16.5%) 23/91 (25.3%)
    Musculoskeletal and connective tiss disorder - Other 5/89 (5.6%) 3/91 (3.3%) 1/91 (1.1%)
    Myalgia 16/89 (18%) 12/91 (13.2%) 6/91 (6.6%)
    Neck pain 6/89 (6.7%) 4/91 (4.4%) 1/91 (1.1%)
    Pain in extremity 19/89 (21.3%) 16/91 (17.6%) 12/91 (13.2%)
    Nervous system disorders
    Dizziness 19/89 (21.3%) 22/91 (24.2%) 28/91 (30.8%)
    Dysgeusia 11/89 (12.4%) 11/91 (12.1%) 16/91 (17.6%)
    Headache 12/89 (13.5%) 14/91 (15.4%) 16/91 (17.6%)
    Paresthesia 5/89 (5.6%) 1/91 (1.1%) 1/91 (1.1%)
    Peripheral sensory neuropathy 9/89 (10.1%) 10/91 (11%) 8/91 (8.8%)
    Tremor 5/89 (5.6%) 3/91 (3.3%) 2/91 (2.2%)
    Psychiatric disorders
    Anxiety 15/89 (16.9%) 13/91 (14.3%) 6/91 (6.6%)
    Confusion 3/89 (3.4%) 5/91 (5.5%) 4/91 (4.4%)
    Depression 9/89 (10.1%) 9/91 (9.9%) 12/91 (13.2%)
    Insomnia 18/89 (20.2%) 15/91 (16.5%) 14/91 (15.4%)
    Renal and urinary disorders
    Chronic kidney disease 1/89 (1.1%) 3/91 (3.3%) 7/91 (7.7%)
    Proteinuria 4/89 (4.5%) 7/91 (7.7%) 1/91 (1.1%)
    Urinary frequency 5/89 (5.6%) 2/91 (2.2%) 2/91 (2.2%)
    Respiratory, thoracic and mediastinal disorders
    Allergic rhinitis 7/89 (7.9%) 5/91 (5.5%) 5/91 (5.5%)
    Cough 24/89 (27%) 26/91 (28.6%) 28/91 (30.8%)
    Dyspnea 41/89 (46.1%) 36/91 (39.6%) 36/91 (39.6%)
    Epistaxis 5/89 (5.6%) 13/91 (14.3%) 11/91 (12.1%)
    Nasal congestion 3/89 (3.4%) 4/91 (4.4%) 6/91 (6.6%)
    Pleural effusion 1/89 (1.1%) 5/91 (5.5%) 4/91 (4.4%)
    Postnasal drip 7/89 (7.9%) 1/91 (1.1%) 1/91 (1.1%)
    Sore throat 7/89 (7.9%) 2/91 (2.2%) 8/91 (8.8%)
    Skin and subcutaneous tissue disorders
    Alopecia 4/89 (4.5%) 3/91 (3.3%) 11/91 (12.1%)
    Dry skin 7/89 (7.9%) 4/91 (4.4%) 5/91 (5.5%)
    Hyperhidrosis 4/89 (4.5%) 4/91 (4.4%) 7/91 (7.7%)
    Pruritus 29/89 (32.6%) 15/91 (16.5%) 7/91 (7.7%)
    Purpura 6/89 (6.7%) 5/91 (5.5%) 7/91 (7.7%)
    Rash maculo-papular 46/89 (51.7%) 20/91 (22%) 16/91 (17.6%)
    Skin and subcutaneous tissue disorders - Other 14/89 (15.7%) 15/91 (16.5%) 5/91 (5.5%)
    Skin ulceration 4/89 (4.5%) 1/91 (1.1%) 6/91 (6.6%)
    Vascular disorders
    Hematoma 5/89 (5.6%) 4/91 (4.4%) 5/91 (5.5%)
    Hot flashes 9/89 (10.1%) 4/91 (4.4%) 5/91 (5.5%)
    Hypertension 10/89 (11.2%) 11/91 (12.1%) 11/91 (12.1%)
    Hypotension 13/89 (14.6%) 5/91 (5.5%) 15/91 (16.5%)

    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 Leukemia Committee Statistician
    Organization SWOG Statistical Center
    Phone 206-667-6597
    Email amoseley@fredhutch.org
    Responsible Party:
    National Cancer Institute (NCI)
    ClinicalTrials.gov Identifier:
    NCT01522976
    Other Study ID Numbers:
    • NCI-2012-00242
    • NCI-2012-00242
    • CDR0000723909
    • SWOG-S1117
    • S1117
    • S1117
    • U10CA180888
    • U10CA032102
    First Posted:
    Feb 1, 2012
    Last Update Posted:
    Dec 1, 2021
    Last Verified:
    Nov 1, 2021