Study of Vidaza Versus Conventional Care Regimens for the Treatment of Acute Myeloid Leukemia (AML)

A Phase 3, Multicenter, Randomized, Open-Label, Study of Azacitidine (Vidaza®) Versus Conventional Care Regimens for the Treatment of Older Subjects With Newly Diagnosed Acute Myeloid Leukemia

The purpose of this study is to compare the effect of azacitidine (Vidaza) to conventional care regimens on overall survival in elderly AML patients.

Study Overview

• Status: Completed
• Conditions: Acute Myeloid Leukemia
• Intervention / Treatment: Drug: Azacitidine; Drug: Conventional Care Regimen

• Study Type: Interventional
• Enrollment (Actual): 488
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • Fitzroy, Australia, 3065
    • St Vincent's hospital
  • New South Wales
    • Randwick, New South Wales, Australia, 2031
      • Prince of Wales Hospital
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Royal Adelaide Hospital
  • Victoria
    • East Melbourne, Victoria, Australia, 3002
      • Peter MacCallum Cancer Centre
    • Footscray, Victoria, Australia, 3011
      • Western Hospital
    • Melbourne, Victoria, Australia, 3050
      • Royal Melbourne Hospital
• Austria
  • Salzburg, Austria, 5020
    • Landeskliniken Salzburg Saint Johanns-Spital, III Medizinische Abteilung
  • Upper Austria
    • Wels, Upper Austria, Austria, 4600
      • Klinikum Wels-Grieskirchen GmbH
  • Vienna
    • Wien, Vienna, Austria, 1160
      • Wilhelminenspital, I Medizinische Abt.
• Belgium
  • La Louvière, Belgium, 7100
    • Centre Hospitalier de Jolimont-Lobbes
  • Hainaut
    • Charleroi, Hainaut, Belgium, 6000
      • Grand Hôpital de Charleroi
  • Namur
    • Yvoir, Namur, Belgium, 5530
      • Cliniques Universitaires UCL de Mont-Godinne
  • Oost-vlaanderen
    • Ghent, Oost-vlaanderen, Belgium, 9000
      • Universitair Ziekenhuis Gent
  • West-vlaanderen
    • Brugge, West-vlaanderen, Belgium, 8000
      • Algemeen Ziekenhuis Sint-Jan
• Canada
  • Calgary, Canada, T2N 2T9
    • Tom Baker Cancer Centre
  • Ontario, Canada, M5G 2M9
    • Princess Margaret Hospital
  • Alberta
    • Edmonton, Alberta, Canada, T6G 2B7
      • University of Alberta Hospital
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3E 0V9
      • Cancer Care Manitoba
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 2Y9
      • Queen Elizabeth II Health Sciences Centre
  • Ontario
    • Ottawa, Ontario, Canada, K1H8L6
      • Ottawa Hospital General Campus
    • Toronto, Ontario, Canada, M4N 3M5
      • Sunnybrook Odette Cancer Centre
  • Quebec
    • Montreal, Quebec, Canada, H1T 2M4
      • Hopital Maisonneuve-Rosemont
    • Montreal, Quebec, Canada, H4J 1C5
      • Hopital Du Sacre Coeur de Montreal
    • Montreal, Quebec, Canada, H2L 4M1
      • Centre Hospitalier de l'Université de Montréal pavilion Notre Dame
• China
  • Beijing, China, 100730
    • Peking Union Medical College Hospital
  • Beijing, China, 100083
    • The Third Hospital of Peking University
  • Jiangsu, China, 210029
    • Peoples Hospital of Jiangsu Province
  • Shanghai, China, 200025
    • Shanghai Ruijin Hospital
  • Shanghai, China, 200433
    • Shanghai Changhai Hospital,the Second Military Medical University
  • Sichuan, China, 610041
    • West China Hospital,Sichuan University
  • Tianjin, China, 3000200
    • Tianjin Blood Disease Hospital
• Czechia
  • Jihormoravsky Kraj
    • Brno, Jihormoravsky Kraj, Czechia, 625 00
      • Fakultni nemocnice Brno
  • Olomoucký Kraj
    • Olomouc, Olomoucký Kraj, Czechia, 775 20
      • Fakultni nemocnice Olomouc, Hemato-onkologicka klinika
  • Praha
    • Praha 2, Praha, Czechia, 128 08
      • Vseobecna fakultni nemocnice v Praze
    • Praha 2, Praha, Czechia, 128 20
      • Ustav hematologie a krevni transfuze
• France
  • Aquitaine, France, 64109
    • Centre Hospitalier de la Cote Basque
  • Lyon Cedex 03, France, 69437
    • Centre Hospitalier Universitaire de Lyon-Hôpital Edouard Herriot
  • Alsace
    • Strasbourg, Alsace, France, 67091
      • Centre Hospitalier Régional Universitaire, Hôpital de Hautepierre
  • ILE-DE-France
    • Bobigny, ILE-DE-France, France, 93009
      • Hospital Avicenne, Service d'hematologie Clinique
  • Ile-de-france
    • Clamart Cedex, Ile-de-france, France, 92141
      • Hopital Percy Clamart
    • Paris Cedex 10, Ile-de-france, France, 75475
      • Hopital Saint Louis
  • Limousin Lorraine
    • Limoges, Limousin Lorraine, France, 87042
      • Centre Hopitalier Universitaire Dupuytren
  • Midi-pyrénées
    • Toulouse Cedex 09, Midi-pyrénées, France, 31059
      • Centre Hospitalier Universitaire de Toulouse
  • Nice
    • Nice Cedex 3, Nice, France, 06202
      • Centre Hospitalier Universitaire de Nice
  • Pays de La Loire
    • Angers cedex 09, Pays de La Loire, France, 49933
      • CHRU d'Angers
    • Nantes Cedex 1, Pays de La Loire, France, 44093
      • Centre Hospitalier Universitaire Nantes, Hotel Dieu
  • Picardie
    • Amiens Cedex 1, Picardie, France, 80054
      • Centre Hospitalier Universitaire d'Amiens, Groupe Hospitalier Sud
  • Provence Alpes Cote D'azur
    • Marseille, Provence Alpes Cote D'azur, France, 13385
      • Hôpital de la Conception
• Germany
  • Baden-wuerttemberg
    • Heidelberg, Baden-wuerttemberg, Germany, 69120
      • Universitätsklinikum Heidelberg
    • Ulm, Baden-wuerttemberg, Germany, 89081
      • Universitatsklinikum Ulm
  • Mecklenburg-vorpommern
    • Rostock, Mecklenburg-vorpommern, Germany, 18057
      • University of Rostock, Div. of Haematology and Oncology
  • Nordrhein-Westfallen
    • Essen, Nordrhein-Westfallen, Germany, 45122
      • Universitatsklinikum Essen, Zentrum fur Tumorforschung und Tumortherapie
  • Nordrhein-westfalen
    • Düesseldorf, Nordrhein-westfalen, Germany, 40211
      • Heinrich-Heine-Universität Düsseldorf
  • Sachsen
    • Leipzig, Sachsen, Germany, 04103
      • Universitätsklinikum Leipzig
  • Thueringen
    • Jena, Thueringen, Germany, 07747
      • Universitatsklinikum Jena
• Israel
  • Beer Yaakov, Israel, 70300
    • Assaf Harofeh Medical Centre
  • Jerusalem, Israel, 91120
    • Hadassah Medical Center
  • Jerusalem, Israel, 91031
    • Shaare Zedek Medical Center
  • Petach Tikva, Israel, 49100
    • Rabin Medical Center
  • Tel Aviv, Israel, 64239
    • Sourasky Medical Center
  • Tel Hashomer, Israel, 52621
    • Chaim Sheba Medical Center - Tel Hashomer, Heart Institute
  • Beersheva
    • Beer Sheva, Beersheva, Israel, 84101
      • Soroka Medical Center
• Italy
  • Alessandria, Italy, 15121
    • Azienda Ospedaliera SS. Antonio E. Biagio E. Cesare Arrigo di Alessandria
  • Ancona, Italy, 60126
    • Azienda Ospedaliera Universitaria - Ospedali Riuniti di Ancona
  • Bari, Italy, 70124
    • Azienda Ospedaliera Policlinico di Bari
  • Bologna, Italy, 40138
    • Azienda Ospedaliera Sant'Orsola Malpighi
  • Firenze, Italy, 50134
    • Azienda Ospedaliero-Universitaria Careggi
  • Reggio Calabria, Italy, 89100
    • Azienda Ospedaliera Bianchi-Melacrino-Morelli
  • Roma, Italy, 00168
    • Policlinico Universitario Agostino Gemelli
  • Roma, Italy, 00161
    • Azienda Policlinico Umberto I di Roma
  • Udine, Italy, 33100
    • Azienda Ospedaliero Universitaria S. Maria della Misericordia di Udine
  • Varese, Italy, 21100
    • Ospedale di Circolo e Fondazione Macchi
  • Potenza
    • Rionero in Vulture, Potenza, Italy, 85028
      • IRCCS Centro di Riferimento Oncologico di Basilicata di Rionero in Vulture
  • Turin
    • Orbassano, Turin, Italy, 10043
      • Azienda Sanitaria Ospedaliera "San Luigi Gonzaga"
• Korea, Republic of
  • Daegu, Korea, Republic of, 700-721
    • Kyungpook National University Hospital
  • Seoul, Korea, Republic of, 138-736
    • Asan Medical Center
  • Seoul, Korea, Republic of, 152-703
    • Korea University Hospital at Guro
  • Seoul, Korea, Republic of, 137-701
    • Seoul Saint Mary's Hospital Seocho-gu
  • Seoul
    • Gangnam-gu, Seoul, Korea, Republic of, 135-710
      • Samsung Medical Center
    • Jongno-gu, Seoul, Korea, Republic of, 110-774
      • Seoul National University Hospital
    • Seodaemun-gu, Seoul, Korea, Republic of, 120-752
      • Yonsei University Health System
• Netherlands
  • Groningen, Netherlands, 9700 RB
    • Universitair Medisch Centrum Groningen
• Poland
  • Dolnoslaskie
    • Wroclaw, Dolnoslaskie, Poland, 50-367
      • Katedra i Klinika Hematologii, Nowotworów Krwi i Transplantacji Szpiku
    • Wroclaw, Dolnoslaskie, Poland, 53-439
      • Dolnośląskie Centrum Transplantacji Komórkowych z Krajowym Bankiem Dawców Szpiku
  • Lodzkie
    • Lódz, Lodzkie, Poland, 93-510
      • Wojewodzki Szpital Specjalistczny im. Mikolaja Kopernika
  • Mazowieckie
    • Warszawa, Mazowieckie, Poland, 02-776
      • Instytut Hematologii i Transfuzjologii
  • Slaskie
    • Katowice, Slaskie, Poland, 40-032
      • Samodzielny Publiczny SK im. A. Mieleckiego Slaskiego Uniwersytetu Medycznego w Katowicach
• Russian Federation
  • Ekaterinburg, Russian Federation, 620137
    • Central City Hospital # 7
  • Moscow, Russian Federation, 125284
    • City Clinical Hospital n.a. S. P. Botkin
  • Nizhniy Novgorod, Russian Federation, 603126
    • State Healthcare Institution "Nizhny Novgorod N.A. Semashko Regional Clinical Hospital"
  • Saint Petersburg, Russian Federation, 197089
    • Saint Petersburg State Academician I.P. Pavlov Medical University
  • Saratov, Russian Federation, 410 028
    • Saratov State Medical University
• Spain
  • Barcelona, Spain, 08036
    • Hospital Clinic i Provincial de Barcelona
  • Madrid, Spain, 28009
    • Hospital General Universitario Gregorio Maranon
  • Salamanca, Spain, 37007
    • Hospital Universitario de Salamanca
  • Sevilla, Spain, 41013
    • Hospital Universitario Virgen del Rocio
  • Valencia, Spain, 46009
    • Hospital Universitario La Fé
  • Asturias
    • Oviedo, Asturias, Spain, 33006
      • Hospital Central de Asturias
  • Baleares
    • Palma de Mallorca, Baleares, Spain, 07198
      • Hospital Son Llatzer
    • Palma de Mallorca, Baleares, Spain, 07014
      • Hospital Son Dureta
• Taiwan
  • Taipei, Taiwan, 10002
    • National Taiwan University Hospital
  • Taipei, Taiwan, 11217
    • Taipei Veterans General Hospital Pei-Tou District
  • Kaohsiung
    • Niao-Sung Hsiang, Kaohsiung, Taiwan, 83301
      • Chang Gung Memorial Hospital, Kaohsiung
• United Kingdom
  • Bournemouth, United Kingdom, BH7 7DW
    • Royal Bournemouth Hospital
  • London, United Kingdom, SE5 9RS
    • King's College Hospital
  • London, United Kingdom, EC1A 7BE
    • Barts and the London NHS Trust
  • Manchester, United Kingdom, M13 9WL
    • Manchester Royal Infirmary
  • Oxford, United Kingdom, OX3 9DS
    • Churchill Hospital
  • Wolverhampton, United Kingdom, WV10 0QP
    • New Cross Hospital
  • Surrey
    • Sutton, Surrey, United Kingdom, SM2 5PT
      • Royal Marsden Hospital
• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Massachusetts General Hospital
  • Texas
    • Houston, Texas, United States, 77030
      • MD Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 65 years and older (Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Diagnosis of one of the following

  • Newly diagnosed de novo acute myeloid leukemia (AML)
  • AML secondary to myelodysplastic syndromes (MDS)
  • AML secondary to exposure to leukemogenic therapy or agents with primary malignancy in remission for at least 2 years
• Bone marrow blasts >30%
• Age ≥ 65 years
• Easter Cooperative Oncology Group (ECOG) 0-2

Exclusion Criteria:

• Previous cytotoxic or biologic treatment for AML (except hydroxyurea)
• Previous treatment with azacitidine, decitabine or cytarabine
• Prior use of targeted therapy agents (e.g., FLT3 inhibitors, other kinase inhibitors)
• AML French American British subtype (FAB M3)
• AML associated with inv(16), t(8;21), t(16;16), t(15:17), or t(9;22) karyotypes
• Prior bone marrow or stem cell transplantation
• Candidate for allogeneic bone marrow or stem cell transplant
• Diagnosis of malignant disease within the previous 12 months (excluding base cell carcinoma, "in-situ" carcinoma of the cervix or breast or other local malignancy excised or irradiated with a high probability of cure)
• Malignant hepatic tumors
• Uncontrolled systemic infection
• Active viral infection with Human Immunodeficiency Virus (HIV) or Hepatitis type B or C
• Use of any experimental drug or therapy within 28 days prior to Day 1

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Azacitidine; Azacitidine daily for 7 days for 28 day cycles until disease progression or unacceptable toxicity	Drug: Azacitidine; 75 mg/m^2 subcutaneous (SC) daily for 7 days for 28 day cycles until disease progression or unacceptable toxicity; Other Names: Vidaza
Active Comparator: Conventional Care Regimen	Drug: Conventional Care Regimen; Physician pre-selects prior to randomization from one of the following: Intensive chemotherapy (cytarabine 100-200 mg/m^2 continuous intravenous infusion for 7 days + anthracycline IV x 3 days) + Best Supportive Care; induction with up to 2 consolidation cycles; Low-dose cytarabine 20 mg subcutaneous (SC) twice a day (BID) for 10 days, for 28 day cycles + BSC; until disease progression or unacceptable toxicity; Best Supportive Care only; until study end

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Kaplan-Meier Estimates for Overall Survival	Overall Survival was defined as the time from randomization to death from any cause. Overall survival was calculated by the formula: date of death - date of randomization + 1. Participants surviving at the end of the follow-up period or who withdrew consent to follow-up were censored at the date of last contact. Participants who were lost to follow-up were censored at the date last known alive.	Day 1 (randomization) to 40 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
One-year Overall Survival Rate	Kaplan Meier methods were used to estimate the 1-year survival probabilities for time to death from any cause. Estimates of the 1-year (365 day) survival probabilities and corresponding 95% confidence intervals (CI) were presented by treatment group. The CI for the difference in the 1-year survival probabilities was derived using Greenwoods variance estimate.	From Day 1 (randomization) to 40 months
Event-free Survival (EFS)	Event-free survival was defined as the interval from the date of randomization to the date of treatment failure, progressive disease, relapse after complete remission (CR) or complete remission with incomplete blood count recovery (CRi), death from any cause, or lost to follow-up, whichever occurs first. Participants who were still alive without any of these events were censored at the date of their last response assessment.	Day 1 (randomization) to date of treatment failure, progressive disease, relapse after Complete Remission (CR) or Complete remission with incomplete blood count recovery (CRi), death from any cause. Day 1 (randomization) to 40 months
Relapse-Free Survival (RFS) for Participants Who Achieved a Complete Remission (CR) or Complete Remission With Incomplete Blood Count Recovery (CRi)	Relapse-free survival was defined as the interval from the date of first documented CR or CRi to the date of relapse, death from any cause, or lost to follow-up, whichever occurred first. Participants who were still alive and in continuous CR or CRi were censored at the date of their last response assessment.	Day 1 of first documented CR or CRi to the date of relapse, death from any cause, or lost to follow-up. Day 1 (randomization) to 40 months
Percentage of Participants Who Achieved a Morphologic CR + CRi as Determined by the Independent Review Committee (IRC) Based on International Working Group (IWG) Response Criteria for Acute Myeloid Leukemia (AML)	A complete remission (CR) is defined as a leukemia-free state defined as less than 5% blasts in a BM aspirate with marrow spicules and with at least 200 nucleated cells (there should be no blasts with Auer rods), an absolute neutrophil count (ANC) of ≥ 1 x 10^9/L, a platelet count ≥ 100 x 10^9/L, and transfusion independence (no transfusions for 1 week prior to each assessment). No duration of these findings is required for confirmation of this response. A CR with incomplete blood count recovery (CRi) is defined as <5% BM blasts with the ANC count < 1 x 10^9/L and/or the platelet count may be < 100 x 10^9/L. Where the date of the hematology assessment used is the earliest on or following the date of the BM sample up to 8 days after the BM date.	Day 1 (randomization) to 40 months
Duration of Remission Assessed by the IRC Based on Kaplan-Meier Estimates	The time from the date CR or CRi was first documented until the date of documented relapse from CR/CRi. Duration of remission was defined only for those participants who achieved a CR or CRi, as determined by the IRC. Participants who were lost to follow-up without documented relapse, or were alive at last follow-up without documented relapse were censored at the date of their last response assessment.	Day 1 (randomization) to 40 months; date of the first documented CR or CRi until date of first documented relapse.
Number of Participants Who Achieved a Cytogenetic Complete Response (CRc-10) as Determined by the IRC.	The CRc is a normal karyotype defined as no clonal abnormalities after review of at least 10 metaphases using conventional cytogenetic techniques. Cytogenetic complete remission rate (CRc) is when the following criteria are met: 1) CR criteria met and 2) an abnormal karyotype is present at baseline and 3) there is reversion to normal karyotype at the time of CR (based on ≥ 10 metaphases), where date of cytogenetic sample = date of BM sample used for the CR assessment	Day 1 (randomization) to 40 months
Number of Participants With Adverse Events (AEs)	AEs = any noxious, unintended, or untoward medical occurrence that may appear or worsen during the course of a study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the participant's health, regardless of cause. Serious AE (SAE) = any AE which results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; constitutes an important medical event. The severity of AEs were graded based upon the participants symptoms according to the Common Terminology Criteria for Adverse Events (CTCAE, Version 4.0); AEs were evaluated for severity according to the following scale: Grade 1 = Mild - transient or mild discomfort; no medical intervention required; Grade 2 = Moderate - mild to moderate limitation in activity; Grade 3 = Severe; Grade 4 = Life threatening; Grade 5 = Death	Day 1 (randomization) up to last visit completed; final data cut off of 28 Feb 2017
Health Related Quality of Life (HRQoL): Change From Baseline in the European Organization for Research and Treatment of Cancer Cancer Quality of Life Questionnaire for Patients With Cancer (EORTC QLQ-C30) Fatigue Domain	The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Fatigue Scale is scored between 0 and 100, with a high score indicating a higher level of symptoms. Negative change from Baseline values indicate reduction in fatigue (i.e. improvement in symptom) and positive values indicate increases in fatigue (i.e. worsening of symptom).	Baseline to Cycle 3; at approximately 3 months
Health Related Quality of Life (HRQoL): Change From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Cancer (EORTC QLQ-C30) Fatigue Domain	The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Fatigue Scale is scored between 0 and 100, with a high score indicating a higher level of symptoms. Negative change from Baseline values indicate reduction in fatigue (i.e. improvement in symptom) and positive values indicate increases in fatigue (i.e. worsening of symptom).	Baseline to Cycle 5, at approximately 5 months
Health Related Quality of Life (HRQoL): Change From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Cancer (EORTC QLQ-C30) Fatigue Domain	The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Fatigue Scale is scored between 0 and 100, with a high score indicating a higher level of symptoms. Negative change from Baseline values indicate reduction in fatigue (i.e. improvement in symptom) and positive values indicate increases in fatigue (i.e. worsening of symptom).	Baseline to Cycle 7, at approximately 7 months
Health Related Quality of Life (HRQoL): Change From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Cancer (EORTC QLQ-C30) Fatigue Domain	The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Fatigue Scale is scored between 0 and 100, with a high score indicating a higher level of symptoms. Negative change from Baseline values indicate reduction in fatigue (i.e. improvement in symptom) and positive values indicate increases in fatigue (i.e. worsening of symptom).	Baseline to Cycle 9, at approximately 9 months
Health Related Quality of Life (HRQoL): Change From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Cancer (EORTC QLQ-C30) Fatigue Domain	The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Fatigue Scale is scored between 0 and 100, with a high score indicating a higher level of symptoms. Negative change from Baseline values indicate reduction in fatigue (i.e. improvement in symptom) and positive values indicate increases in fatigue (i.e. worsening of symptom).	Baseline to End of Study; at approximately 11-12 months
HRQoL: Change From Baseline in the EORTC QLQ-C30 Dyspnea	The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Dyspnea scale is scored between 0 and 100, with a high score indicating a higher level of symptoms. Negative change from Baseline values indicate decreased dyspnea (i.e. improvement in symptom) and positive values indicate increased dyspnea (i.e. worsening of symptom).	Baseline to Cycle 3, at approximately 3 months
HRQoL: Change From Baseline in the EORTC QLQ-C30 Dyspnea	The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Dyspnea scale is scored between 0 and 100, with a high score indicating a higher level of symptoms. Negative change from Baseline values indicate decreased dyspnea (i.e. improvement in symptom) and positive values indicate increased dyspnea (i.e. worsening of symptom).	Baseline to Cycle 5, at approximately 5 months
HRQoL: Change From Baseline in the EORTC QLQ-C30 Dyspnea	The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Dyspnea scale is scored between 0 and 100, with a high score indicating a higher level of symptoms. Negative change from Baseline values indicate decreased dyspnea (i.e. improvement in symptom) and positive values indicate increased dyspnea (i.e. worsening of symptom).	Baseline to Cycle 7, at approximately 7 months
HRQoL: Change From Baseline in the EORTC QLQ-C30 Dyspnea	The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Dyspnea scale is scored between 0 and 100, with a high score indicating a higher level of symptoms. Negative change from Baseline values indicate decreased dyspnea (i.e. improvement in symptom) and positive values indicate increased dyspnea (i.e. worsening of symptom).	Baseline to Cycle 9, at approximately 9 months
HRQoL: Change From Baseline in the EORTC QLQ-C30 Dyspnea	The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Dyspnea scale is scored between 0 and 100, with a high score indicating a higher level of symptoms. Negative change from Baseline values indicate decreased dyspnea (i.e. improvement in symptom) and positive values indicate increased dyspnea (i.e. worsening of symptom).	Baseline to end of study, at approximately 11-12 months
HRQoL: Change From Baseline in the EORTC QLQ-C30 Physical Functioning Domain	The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 PhysicalFunctioning Scale is scored between 0 and 100, with a high score indicating better functioning. Negative change from Baseline values indicate deterioration in functioning and positive values indicate improvement.	Baseline to Cycle 3, at approximately 3 months
HRQoL: Change From Baseline in the EORTC QLQ-C30 Physical Functioning Domain	The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 PhysicalFunctioning Scale is scored between 0 and 100, with a high score indicating better functioning. Negative change from Baseline values indicate deterioration in functioning and positive values indicate improvement.	Baseline to Cycle 5, at approximately 5 months
HRQoL: Change From Baseline in the EORTC QLQ-C30 Physical Functioning Domain	The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 PhysicalFunctioning Scale is scored between 0 and 100, with a high score indicating better functioning. Negative change from Baseline values indicate deterioration in functioning and positive values indicate improvement.	Baseline to Cycle 7, at approximately 7 months
HRQoL: Change From Baseline in the EORTC QLQ-C30 Physical Functioning Domain	The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 PhysicalFunctioning Scale is scored between 0 and 100, with a high score indicating better functioning. Negative change from Baseline values indicate deterioration in functioning and positive values indicate improvement.	Baseline to Cycle 9, at approximately 9 months
HRQoL: Change From Baseline in the EORTC QLQ-C30 Physical Functioning Domain	The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 PhysicalFunctioning Scale is scored between 0 and 100, with a high score indicating better functioning. Negative change from Baseline values indicate deterioration in functioning and positive values indicate improvement.	Baseline to end of study, at approximately 11-12 months
HRQoL: Change From Baseline in the EORTC QLQ-C30 Global Health Status-/Quality of Life Domain	The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Global Health Status/QOL scale is scored between 0 and 100, with a high score indicating better Global Health Status/QOL. Negative change from Baseline values indicate deterioration in Global Health Status/QOL and positive values indicate improvement.	Baseline to Cycle 3, at approximately 3 months
HRQoL: Change From Baseline in the EORTC QLQ-C30 Global Health Status-/Quality of Life Domain	The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Global Health Status/QOL scale is scored between 0 and 100, with a high score indicating better Global Health Status/QOL. Negative change from Baseline values indicate deterioration in Global Health Status/QOL and positive values indicate improvement.	Baseline to Cycle 5, at approximately 5 months
HRQoL: Change From Baseline in the EORTC QLQ-C30 Global Health Status-/Quality of Life Domain	The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Global Health Status/QOL scale is scored between 0 and 100, with a high score indicating better Global Health Status/QOL. Negative change from Baseline values indicate deterioration in Global Health Status/QOL and positive values indicate improvement.	Baseline to Cycle 7, at approximately 7 months
HRQoL: Change From Baseline in the EORTC QLQ-C30 Global Health Status-/Quality of Life Domain	The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Global Health Status/QOL scale is scored between 0 and 100, with a high score indicating better Global Health Status/QOL. Negative change from Baseline values indicate deterioration in Global Health Status/QOL and positive values indicate improvement.	Baseline to Cycle 9, at approximately 9 months
HRQoL: Change From Baseline in the EORTC QLQ-C30 Global Health Status-/Quality of Life Domain	The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Global Health Status/QOL scale is scored between 0 and 100, with a high score indicating better Global Health Status/QOL. Negative change from Baseline values indicate deterioration in Global Health Status/QOL and positive values indicate improvement.	Baseline to end of study, at approximately 11-12 months
Healthcare Resource Utilization (HRU): Number of Inpatient Hospitalizations	HRU was defined as any consumption of healthcare resources directly or indirectly related to the treatment of the patient. HRU Analysis may help in evaluating potential costs and budget impact of new treatments from a payer perspective.	Day 1 (randomization) to 40 months
Healthcare Resource Utilization (HRU): Rate of Inpatient Hospitalizations Per Year	HRU was defined as any consumption of healthcare resources directly or indirectly related to the treatment of the patient. HRU Analysis may help in evaluating potential costs and budget impact of new treatments from a payer perspective. The rate of inpatient hospitalizations per patient year was calculated as the total number of hospitalizations divided by the total number of patient-years followed in the study period. Patient-years (PY) were calculated as the duration from baseline to last available HRQL assessment for each patient.	Day 1 (randomization) to 40 months
HRU: Number of Participants Receiving Transfusions	Count of study participants who had transfusions during the treatment phase. HRU is defined as any consumption of healthcare resources directly or indirectly related to the treatment of the patient. HRU Analysis may help in evaluating potential costs and budget impact of new treatments from a payer perspective.	Day 1 (randomization) to 40 months
HRU: Rate of Transfusions Per Patient Year	HRU is defined as any consumption of healthcare resources directly or indirectly related to the treatment of the patient. HRU Analysis may help in evaluating potential costs and budget impact of new treatments from a payer perspective. The rate of transfusions per patient year was calculated as the total number of transfusions divided by the total number of patient-years followed in the study period. Patient-years (PY) were calculated as the duration from baseline to last available HRQL assessment for each patient.	Day 1 (randomization) to 40 months
Number of Participants in the Extension Phase With Treatment Emergent Adverse Events (TEAEs)	AEs = any noxious, unintended, or untoward medical occurrence that may appear or worsen during the course of a study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the participant's health, regardless of cause. Serious AE (SAE) = any AE which results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; constitutes an important medical event. The severity of AEs were graded based upon the participants symptoms according to the Common Terminology Criteria for Adverse Events (CTCAE, Version 4.0); AEs were evaluated for severity according to the following scale: Grade 1 = Mild - transient or mild discomfort; no medical intervention required; Grade 2 = Moderate - mild to moderate limitation in activity; Grade 3 = Severe; Grade 4 = Life threatening; Grade 5 = Death	From the date of informed consent for the Extension Phase through to the date of last dose of study drug + 28 days up to last visit completed 24 July 2016; maximum duration of exposure to Azacitidine was 871 days

Collaborators and Investigators

• Sponsor: Celgene
• Investigators: Study Director: C L Beach, PharmD, Celgene Corporation

Publications and helpful links

General Publications

• Seymour JF, Dohner H, Butrym A, Wierzbowska A, Selleslag D, Jang JH, Kumar R, Cavenagh J, Schuh AC, Candoni A, Recher C, Sandhu I, Del Castillo TB, Al-Ali HK, Falantes J, Stone RM, Minden MD, Weaver J, Songer S, Beach CL, Dombret H. Azacitidine improves clinical outcomes in older patients with acute myeloid leukaemia with myelodysplasia-related changes compared with conventional care regimens. BMC Cancer. 2017 Dec 14;17(1):852. doi: 10.1186/s12885-017-3803-6.
• Dombret H, Seymour JF, Butrym A, Wierzbowska A, Selleslag D, Jang JH, Kumar R, Cavenagh J, Schuh AC, Candoni A, Recher C, Sandhu I, Bernal del Castillo T, Al-Ali HK, Martinelli G, Falantes J, Noppeney R, Stone RM, Minden MD, McIntyre H, Songer S, Lucy LM, Beach CL, Dohner H. International phase 3 study of azacitidine vs conventional care regimens in older patients with newly diagnosed AML with >30% blasts. Blood. 2015 Jul 16;126(3):291-9. doi: 10.1182/blood-2015-01-621664. Epub 2015 May 18.

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2010
• Primary Completion (Actual): January 22, 2014
• Study Completion (Actual): July 25, 2016

Study Registration Dates

• First Submitted: February 16, 2010
• First Submitted That Met QC Criteria: February 22, 2010
• First Posted (Estimate): February 24, 2010

Study Record Updates

• Last Update Posted (Actual): August 29, 2017
• Last Update Submitted That Met QC Criteria: August 25, 2017
• Last Verified: August 1, 2017

More Information

Terms related to this study

• Keywords: Acute Myeloid Leukemia; Cytarabine; azacitidine; Low Dose Cytarabine; Vidaza; Celgene; Intensive Chemotherapy
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Azacitidine
• Other Study ID Numbers: AZA-AML-001

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No