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

Acute Myeloid Leukemia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01074047
• Other study ID #: AZA-AML-001
• Status: Completed
• Phase: Phase 3
• First received: February 16, 2010
• Last updated: August 25, 2017
• Start date: June 1, 2010
• Est. completion date: July 25, 2016

Study information

• Verified date: August 2017
• Source: Celgene
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 488
• Est. completion date: July 25, 2016
• Est. primary completion date: January 22, 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 65 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Acute Myeloid Leukemia
• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute

Intervention

Drug:
• Azacitidine
75 mg/m^2 subcutaneous (SC) daily for 7 days for 28 day cycles until disease progression or unacceptable toxicity
• 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

Locations

Country	Name	City	State
Australia	Royal Adelaide Hospital	Adelaide	South Australia
Australia	Peter MacCallum Cancer Centre	East Melbourne	Victoria
Australia	St Vincent's Hospital	Fitzroy
Australia	Western Hospital	Footscray	Victoria
Australia	Royal Melbourne Hospital	Melbourne	Victoria
Australia	Prince of Wales Hospital	Randwick	New South Wales
Austria	Landeskliniken Salzburg Saint Johanns-Spital, III Medizinische Abteilung	Salzburg
Austria	Klinikum Wels-Grieskirchen GmbH	Wels	Upper Austria
Austria	Wilhelminenspital, I Medizinische Abt.	Wien	Vienna
Belgium	Algemeen Ziekenhuis Sint-Jan	Brugge	West-vlaanderen
Belgium	Grand Hôpital de Charleroi	Charleroi	Hainaut
Belgium	Universitair Ziekenhuis Gent	Ghent	Oost-vlaanderen
Belgium	Centre Hospitalier de Jolimont-Lobbes	La Louvière
Belgium	Cliniques Universitaires UCL de Mont-Godinne	Yvoir	Namur
Canada	Tom Baker Cancer Centre	Calgary
Canada	University of Alberta Hospital	Edmonton	Alberta
Canada	Queen Elizabeth II Health Sciences Centre	Halifax	Nova Scotia
Canada	Centre Hospitalier de l'Université de Montréal pavilion Notre Dame	Montreal	Quebec
Canada	Hopital du Sacre Coeur de Montréal	Montreal	Quebec
Canada	Hopital Maisonneuve-Rosemont	Montreal	Quebec
Canada	Princess Margaret Hospital	Ontario
Canada	Ottawa Hospital General Campus	Ottawa	Ontario
Canada	Sunnybrook Odette Cancer Centre	Toronto	Ontario
Canada	Cancer Care Manitoba	Winnipeg	Manitoba
China	Peking Union Medical College Hospital	Beijing
China	The Third Hospital of Peking University	Beijing
China	Peoples Hospital of Jiangsu Province	Jiangsu
China	Shanghai Changhai Hospital,the Second Military Medical University	Shanghai
China	Shanghai Ruijin Hospital	Shanghai
China	West China Hospital,Sichuan University	Sichuan
China	Tianjin Blood Disease Hospital	Tianjin
Czechia	Fakultni nemocnice Brno	Brno	Jihormoravsky Kraj
Czechia	Fakultni nemocnice Olomouc, hemato-onkologicka klinika	Olomouc	Olomoucký Kraj
Czechia	Ustav hematologie a krevni transfuze	Praha 2	Praha
Czechia	Vseobecna Fakultni Nemocnice v Praze	Praha 2	Praha
France	Centre Hospitalier Universitaire d'Amiens, Groupe Hospitalier Sud	Amiens Cedex 1	Picardie
France	CHRU d'Angers	Angers cedex 09	Pays de La Loire
France	Centre Hospitalier de la Cote Basque	Aquitaine
France	Hospital Avicenne, Service d'hematologie Clinique	Bobigny	ILE-DE-France
France	Hopital Percy Clamart	Clamart Cedex	Ile-de-france
France	Centre Hopitalier Universitaire Dupuytren	Limoges	Limousin Lorraine
France	Centre Hospitalier Universitaire de Lyon-Hôpital Edouard Herriot	Lyon Cedex 03
France	Hôpital de la Conception	Marseille	Provence Alpes Cote D'azur
France	Centre Hospitalier Universitaire Nantes, Hotel Dieu	Nantes Cedex 1	Pays de La Loire
France	Centre Hospitalier Universitaire de Nice	Nice Cedex 3	Nice
France	Hôpital Saint Louis	Paris Cedex 10	Ile-de-france
France	Centre Hospitalier Régional Universitaire, Hôpital de Hautepierre	Strasbourg	Alsace
France	Centre Hospitalier Universitaire de Toulouse	Toulouse Cedex 09	Midi-pyrénées
Germany	Heinrich-Heine-Universität Düsseldorf	Düesseldorf	Nordrhein-westfalen
Germany	Universitatsklinikum Essen, Zentrum fur Tumorforschung und Tumortherapie	Essen	Nordrhein-Westfallen
Germany	Universitatsklinikum Heidelberg	Heidelberg	Baden-wuerttemberg
Germany	Universitätsklinikum Jena	Jena	Thueringen
Germany	Universitätsklinikum Leipzig	Leipzig	Sachsen
Germany	University of Rostock, Div. of Haematology and Oncology	Rostock	Mecklenburg-vorpommern
Germany	Universitätsklinikum Ulm	Ulm	Baden-wuerttemberg
Israel	Soroka Medical Center	Beer Sheva	Beersheva
Israel	Assaf Harofeh Medical Centre	Beer Yaakov
Israel	Hadassah Medical Center	Jerusalem
Israel	Shaare Zedek Medical Center	Jerusalem
Israel	Rabin Medical Center	Petach Tikva
Israel	Sourasky Medical Center	Tel Aviv
Israel	Chaim Sheba Medical Center - Tel Hashomer, Heart Institute	Tel Hashomer
Italy	Azienda Ospedaliera SS. Antonio E. Biagio E. Cesare Arrigo di Alessandria	Alessandria
Italy	Azienda Ospedaliera Universitaria - Ospedali Riuniti di Ancona	Ancona
Italy	Azienda Ospedaliera Policlinico di Bari	Bari
Italy	Azienda Ospedaliera Sant'Orsola Malpighi	Bologna
Italy	Azienda Ospedaliero-Universitaria Careggi	Firenze
Italy	Azienda Sanitaria Ospedaliera "San Luigi Gonzaga"	Orbassano	Turin
Italy	Azienda Ospedaliera Bianchi-Melacrino-Morelli	Reggio Calabria
Italy	IRCCS Centro di Riferimento Oncologico di Basilicata di Rionero in Vulture	Rionero in Vulture	Potenza
Italy	Azienda Policlinico Umberto I di Roma	Roma
Italy	Policlinico Universitario Agostino Gemelli	Roma
Italy	Azienda Ospedaliero Universitaria S. Maria della Misericordia di Udine	Udine
Italy	Ospedale di Circolo e Fondazione Macchi	Varese
Korea, Republic of	Kyungpook National University Hospital	Daegu
Korea, Republic of	Samsung Medical Center	Gangnam-gu	Seoul
Korea, Republic of	Seoul National University Hospital	Jongno-gu	Seoul
Korea, Republic of	Yonsei University Health System	Seodaemun-gu	Seoul
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Korea University Hospital at Guro	Seoul
Korea, Republic of	Seoul Saint Mary's Hospital Seocho-gu	Seoul
Netherlands	Universitair Medisch Centrum Groningen	Groningen
Poland	Samodzielny Publiczny SK im. A. Mieleckiego Slaskiego Uniwersytetu Medycznego w Katowicach	Katowice	Slaskie
Poland	Wojewodzki Szpital Specjalistczny im. Mikolaja Kopernika	Lódz	Lodzkie
Poland	Instytut Hematologii i Transfuzjologii	Warszawa	Mazowieckie
Poland	Dolnoslaskie Centrum Transplantacji Komórkowych z Krajowym Bankiem Dawców Szpiku	Wroclaw	Dolnoslaskie
Poland	Katedra i Klinika Hematologii, Nowotworów Krwi i Transplantacji Szpiku	Wroclaw	Dolnoslaskie
Russian Federation	Central City Hospital # 7	Ekaterinburg
Russian Federation	City Clinical Hospital n.a. S. P. Botkin	Moscow
Russian Federation	State Healthcare Institution "Nizhny Novgorod N.A. Semashko Regional Clinical Hospital"	Nizhniy Novgorod
Russian Federation	Saint Petersburg State Academician I.P. Pavlov Medical University	Saint Petersburg
Russian Federation	Saratov State Medical University	Saratov
Spain	Hospital Clinic i Provincial de Barcelona	Barcelona
Spain	Hospital General Universitario Gregorio Marañon	Madrid
Spain	Hospital Central de Asturias	Oviedo	Asturias
Spain	Hospital Son Dureta	Palma de Mallorca	Baleares
Spain	Hospital Son Llàtzer	Palma de Mallorca	Baleares
Spain	Hospital Universitario de Salamanca	Salamanca
Spain	Hospital Universitario Virgen del Rocío	Sevilla
Spain	Hospital Universitario La Fe	Valencia
Taiwan	Chang Gung Memorial Hospital, Kaohsiung	Niao-Sung Hsiang	Kaohsiung
Taiwan	National Taiwan University Hospital	Taipei
Taiwan	Taipei Veterans General Hospital Pei-Tou District	Taipei
United Kingdom	Royal Bournemouth Hospital	Bournemouth
United Kingdom	Barts and the London NHS Trust	London
United Kingdom	King's College Hospital	London
United Kingdom	Manchester Royal Infirmary	Manchester
United Kingdom	Churchill Hospital	Oxford
United Kingdom	Royal Marsden Hospital	Sutton	Surrey
United Kingdom	New Cross Hospital	Wolverhampton
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	MD Anderson Cancer Center	Houston	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Celgene

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Belgium,  Canada,  China,  Czechia,  France,  Germany,  Israel,  Italy,  Korea, Republic of,  Netherlands,  Poland,  Russian Federation,  Spain,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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.
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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