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

• Sponsor: Celgene (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01074047
• Collaborator: (none)
• Enrollment: 488
• Locations: 112
• Arms: 2
• Actual Duration (Months): 73.8
• Patients Per Site: 4.4
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Acute Myeloid Leukemia	Drug: Azacitidine; Drug: Conventional Care Regimen	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 488 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: Jun 1, 2010
• Actual Primary Completion Date: Jan 22, 2014
• Actual Study Completion Date: Jul 25, 2016

Arms and Interventions

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 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

Outcome Measures

Primary Outcome Measures

1. Kaplan-Meier Estimates for Overall Survival [Day 1 (randomization) to 40 months]

   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.

Secondary Outcome Measures

1. One-year Overall Survival Rate [From Day 1 (randomization) to 40 months]

   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.

2. Event-free Survival (EFS) [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]

   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.

3. Relapse-Free Survival (RFS) for Participants Who Achieved a Complete Remission (CR) or Complete Remission With Incomplete Blood Count Recovery (CRi) [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]

   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.

4. 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) [Day 1 (randomization) to 40 months]

   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.

5. Duration of Remission Assessed by the IRC Based on Kaplan-Meier Estimates [Day 1 (randomization) to 40 months; date of the first documented CR or CRi until date of first documented relapse.]

   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.

6. Number of Participants Who Achieved a Cytogenetic Complete Response (CRc-10) as Determined by the IRC. [Day 1 (randomization) to 40 months]

   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

7. Number of Participants With Adverse Events (AEs) [Day 1 (randomization) up to last visit completed; final data cut off of 28 Feb 2017]

   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

8. 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 [Baseline to Cycle 3; at approximately 3 months]

   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).

9. 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 [Baseline to Cycle 5, at approximately 5 months]

   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).

10. 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 [Baseline to Cycle 7, at approximately 7 months]

    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).

11. 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 [Baseline to Cycle 9, at approximately 9 months]

    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).

12. 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 [Baseline to End of Study; at approximately 11-12 months]

    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).

13. HRQoL: Change From Baseline in the EORTC QLQ-C30 Dyspnea [Baseline to Cycle 3, at approximately 3 months]

    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).

14. HRQoL: Change From Baseline in the EORTC QLQ-C30 Dyspnea [Baseline to Cycle 5, at approximately 5 months]

    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).

15. HRQoL: Change From Baseline in the EORTC QLQ-C30 Dyspnea [Baseline to Cycle 7, at approximately 7 months]

    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).

16. HRQoL: Change From Baseline in the EORTC QLQ-C30 Dyspnea [Baseline to Cycle 9, at approximately 9 months]

    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).

17. HRQoL: Change From Baseline in the EORTC QLQ-C30 Dyspnea [Baseline to end of study, at approximately 11-12 months]

    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).

18. HRQoL: Change From Baseline in the EORTC QLQ-C30 Physical Functioning Domain [Baseline to Cycle 3, at approximately 3 months]

    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.

19. HRQoL: Change From Baseline in the EORTC QLQ-C30 Physical Functioning Domain [Baseline to Cycle 5, at approximately 5 months]

    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.

20. HRQoL: Change From Baseline in the EORTC QLQ-C30 Physical Functioning Domain [Baseline to Cycle 7, at approximately 7 months]

    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.

21. HRQoL: Change From Baseline in the EORTC QLQ-C30 Physical Functioning Domain [Baseline to Cycle 9, at approximately 9 months]

    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.

22. HRQoL: Change From Baseline in the EORTC QLQ-C30 Physical Functioning Domain [Baseline to end of study, at approximately 11-12 months]

    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.

23. HRQoL: Change From Baseline in the EORTC QLQ-C30 Global Health Status-/Quality of Life Domain [Baseline to Cycle 3, at approximately 3 months]

    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.

24. HRQoL: Change From Baseline in the EORTC QLQ-C30 Global Health Status-/Quality of Life Domain [Baseline to Cycle 5, at approximately 5 months]

    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.

25. HRQoL: Change From Baseline in the EORTC QLQ-C30 Global Health Status-/Quality of Life Domain [Baseline to Cycle 7, at approximately 7 months]

    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.

26. HRQoL: Change From Baseline in the EORTC QLQ-C30 Global Health Status-/Quality of Life Domain [Baseline to Cycle 9, at approximately 9 months]

    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.

27. HRQoL: Change From Baseline in the EORTC QLQ-C30 Global Health Status-/Quality of Life Domain [Baseline to end of study, at approximately 11-12 months]

    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.

28. Healthcare Resource Utilization (HRU): Number of Inpatient Hospitalizations [Day 1 (randomization) to 40 months]

    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.

29. Healthcare Resource Utilization (HRU): Rate of Inpatient Hospitalizations Per Year [Day 1 (randomization) to 40 months]

    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.

30. HRU: Number of Participants Receiving Transfusions [Day 1 (randomization) to 40 months]

    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.

31. HRU: Rate of Transfusions Per Patient Year [Day 1 (randomization) to 40 months]

    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.

32. Number of Participants in the Extension Phase With Treatment Emergent Adverse Events (TEAEs) [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]

    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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 65 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

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

Sponsors and Collaborators

• Celgene

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Celgene
• ClinicalTrials.gov Identifier: NCT01074047
• Other Study ID Numbers: AZA-AML-001
• First Posted: Feb 24, 2010
• Last Update Posted: Aug 29, 2017
• Last Verified: Aug 1, 2017

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Celgene: Acute Myeloid Leukemia; Cytarabine; Vidaza; azacitidine; Intensive Chemotherapy; Low Dose Cytarabine; Celgene
• Additional relevant MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Azacitidine

Study Results

Participant Flow

Recruitment Details	This was a multicenter, international Phase 3 study conducted at 107 investigational sites in 18 countries including South Korea, China, Taiwan, Australia, Canada, United States, Poland, Russia, Czech Republic, Israel, France, Italy, Spain, Germany, United Kingdom, Belgium, Austria and the Netherlands.

Arm/Group Title	Azacitidine (AZA)	Conventional Care Regimens (CCR)
Arm/Group Description	Azacitidine 75 mg/m2/day by subcutaneous injection [SC] for 7 days every 28 days, with a 21 day rest period (optimally for at least 6 cycles) plus best supportive care as needed, including antibiotics and blood product transfusions, growth factors, per physician's discretion.	CCRs included: 1 Intensive Chemotherapy: Cytarabine 100-200 mg/m2 as a continuous intravenous infusion (CIVI) for 7 days and daunorubicin 45 to 60 mg/m² daily (QD) IV on Days 1, 2 and 3 or Idarubicin 9-12 mg/m² IV QD for 3 days. Consolidation Therapy (Cycle 2 and 3) = Cytarabine 100-200 mg/m2 as a CIVI for 3 to 7 days and daunorubicin 45 to 60 mg/m² QD or Idarubicin 9-12 mg/m² IV QD on Days 1 and 2. The first consolidation therapy started between Day 28 and Day 70 from start of induction therapy, upon recovery of absolute neutrophil count (ANC) above 1.0 x 10^9/L and platelets above 75 x 10^9/L. The second cycle started between Day 28 and Day 70 from start of first consolidation therapy. Best supportive care (BSC) of antibiotics and transfusions, were given as needed 2 Low-dose cytarabine 20 mg subcutaneously twice a day (BID) for 10 days every 28 days, plus BSC 3 BSC only = transfusion of blood products, antibiotics, antifungals and nutritional help
Period Title: Treatment Phase
STARTED	241	247
Treated Population	236	240
Safety Population	236	235
Evaluable Population	179	191
COMPLETED	24	13
NOT COMPLETED	217	234
Period Title: Treatment Phase
STARTED	140	163
COMPLETED	16	27
NOT COMPLETED	124	136
Period Title: Treatment Phase
STARTED	22	0
Safety Population	22	0
COMPLETED	0	0
NOT COMPLETED	22	0

Baseline Characteristics

Arm/Group Title	Azacitidine (AZA)	Conventional Care Regimens (CCR)	Total
Arm/Group Description	Azacitidine 75 mg/m2/day by subcutaneous injection [SC] for 7 days every 28 days, with a 21 day rest period (optimally for at least 6 cycles) plus best supportive care as needed, including antibiotics and blood product transfusions, growth factors, per physician's discretion.	#1 Intensive Chemotherapy: Cytarabine 100-200 mg/m^2 as a continuous intravenous infusion (CIVI) for 7 days and daunorubicin 45 to 60 mg/m^² daily (QD) IV on Days 1, 2 and 3 or Idarubicin 9-12 mg/m^² IV QD for 3 days. Consolidation Therapy (Cycle 2 and 3) = Cytarabine 100-200 mg/m^2 as a CIVI for 3 to 7 days and daunorubicin 45 to 60 mg/m^² QD or Idarubicin 9-12 mg/m^² IV QD on Days 1 and 2. Consolidation therapy started between Day 28 and Day 70 from start of induction therapy, upon recovery of absolute neutrophil count (ANC) above 1.0 x 10^9/L and platelets above 75 x 10^9/L. The second cycle started between Day 28 and Day 70 from start of first consolidation therapy. Best supportive care (BSC) of antibiotics and transfusions, were given as needed. # 2 Low-dose cytarabine 20 mg SC twice a day (BID) for 10 days every 28 days, plus BSC # 3 BSC only includes transfusion of blood products, antibiotics, antifungals and nutritional help.	Total of all reporting groups
Overall Participants	241	247	488
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	75.4 (5.60)	75.1 (5.57)	75.2 (5.58)
Age, Customized (participants) [Number]
<75 years	103 42.7%	120 48.6%	223 45.7%
≥75 years	138 57.3%	127 51.4%	265 54.3%
Sex: Female, Male (Count of Participants)
Female	102 42.3%	98 39.7%	200 41%
Male	139 57.7%	149 60.3%	288 59%
Eastern Cooperative Oncology Group (ECOG) Performance Status (participants) [Number]
0 = Fully Active	54 22.4%	57 23.1%	111 22.7%
1 = Restrictive but Ambulatory	132 54.8%	132 53.4%	264 54.1%
2 = Ambulatory but unable to work	55 22.8%	58 23.5%	113 23.2%
3 = Limited Self Care	0 0%	0 0%	0 0%
4 = Completely disabled	0 0%	0 0%	0 0%
World Health Organization Acute Myeloid Leukemia (AML) Classification (participants) [Number]
AML with myelodysplasia-related changes	75 31.1%	83 33.6%	158 32.4%
Therapy-related myeloid neoplasms	8 3.3%	12 4.9%	158 32.4%
AML with recurrent genetic abnormalities	5 2.1%	9 3.6%	14 2.9%
AML not otherwise specified	153 63.5%	143 57.9%	296 60.7%
Bone Marrow-Blasts Counts (Percentage of Bone Marrow Blasts) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Percentage of Bone Marrow Blasts]	66.6 (24.71)	70.2 (22.28)	68.5 (23.56)

Outcome Measures

1. Primary Outcome

Title	Kaplan-Meier Estimates for Overall Survival
Description	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.
Time Frame	Day 1 (randomization) to 40 months

Outcome Measure Data

Analysis Population Description

The intent-to-treat (ITT) population was defined as all participants who were randomized, independent of whether they received study treatment or not. Includes participants who died and participants who were censored

Arm/Group Title	Azacitidine (AZA)	Conventional Care Regimens (CCR)
Arm/Group Description	Azacitidine 75 mg/m2/day by subcutaneous injection [SC] for 7 days every 28 days, with a 21 day rest period (optimally for at least 6 cycles) plus best supportive care as needed, including antibiotics and blood product transfusions, growth factors, per physician's discretion.	CCRs included: #1 Intensive Chemotherapy: Cytarabine 100-200 mg/m^2 as a continuous intravenous infusion (CIVI) for 7 days and daunorubicin 45 to 60 mg/m^² daily (QD) IV on Days 1, 2 and 3 or Idarubicin 9-12 mg/m^² IV QD for 3 days. Consolidation Therapy (Cycle 2 and 3) = Cytarabine 100-200 mg/m^2 as a CIVI for 3 to 7 days and daunorubicin 45 to 60 mg/m^² QD or Idarubicin 9-12 mg/m^² IV QD on Days 1 and 2. The first consolidation therapy started between Day 28 and Day 70 from start of induction therapy, upon recovery of absolute neutrophil count (ANC) above 1.0 x 10^9/L and platelets above 75 x 10^9/L. The second cycle started between Day 28 and Day 70 from start of first consolidation therapy. Best supportive care (BSC) of antibiotics and transfusions, were given as needed # 2 Low-dose cytarabine 20 mg subcutaneously twice a day (BID) for 10 days every 28 days, plus BSC # 3 BSC only = transfusion of blood products, antibiotics, antifungals and nutritional help
Measure Participants	241	247
Median (95% Confidence Interval) [months]	10.4	6.5

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Azacitidine (AZA), Conventional Care Regimens (CCR)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0829
	Comments
	Method	Log Rank
	Comments	The p-value is two-sided from an unstratified log-rank test
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.84
	Confidence Interval	(2-Sided) 95%; 0.69 to 1.02
	Parameter Dispersion	Type: Value:
	Estimation Comments	The hazard ratio is from a Cox proportional hazards model stratified by ECOG performance status and cytogenetic risk status.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Azacitidine (AZA), Conventional Care Regimens (CCR)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1009
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.85
	Confidence Interval	(2-Sided) 95%; 0.69 to 1.03
	Parameter Dispersion	Type: Value:
	Estimation Comments	The hazard ratio is from a Cox proportional hazards model stratified by ECOG performance status and cytogenetic risk status.

2. Secondary Outcome

Title	One-year Overall Survival Rate
Description	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.
Time Frame	From Day 1 (randomization) to 40 months

Outcome Measure Data

Analysis Population Description

The intent-to-treat (ITT) population was defined as all participants who were randomized, independent of whether they received study treatment or not. Includes participants who died and participants who were censored

Arm/Group Title	Azacitidine (AZA)	Conventional Care Regimen
Arm/Group Description	Azacitidine 75 mg/m2/day by subcutaneous injection [SC] for 7 days every 28 days, with a 21 day rest period (optimally for at least 6 cycles) plus best supportive care as needed, including antibiotics and blood product transfusions, growth factors, per physician's discretion.	CCRs included: #1 Intensive Chemotherapy: Cytarabine 100-200 mg/m^2 as a continuous intravenous infusion (CIVI) for 7 days and daunorubicin 45 to 60 mg/m^² daily (QD) IV on Days 1, 2 and 3 or Idarubicin 9-12 mg/m^² IV QD for 3 days. Consolidation Therapy (Cycle 2 and 3) = Cytarabine 100-200 mg/m^2 as a CIVI for 3 to 7 days and daunorubicin 45 to 60 mg/m^² QD or Idarubicin 9-12 mg/m^² IV QD on Days 1 and 2. The first consolidation therapy started between Day 28 and Day 70 from start of induction therapy, upon recovery of absolute neutrophil count (ANC) above 1.0 x 10^9/L and platelets above 75 x 10^9/L. The second cycle started between Day 28 and Day 70 from start of first consolidation therapy. Best supportive care (BSC) of antibiotics and transfusions, were given as needed # 2 Low-dose cytarabine 20 mg subcutaneously twice a day (BID) for 10 days every 28 days, plus BSC # 3 BSC only = transfusion of blood products, antibiotics, antifungals and nutritional help
Measure Participants	241	247
Number (95% Confidence Interval) [percentage of participants]	46.5 19.3%	34.3 13.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Azacitidine (AZA), Conventional Care Regimens (CCR)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference
	Estimated Value	12.26
	Confidence Interval	(2-Sided) 95%; 3.5 to 21.0
	Parameter Dispersion	Type: Value:
	Estimation Comments	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.

3. Secondary Outcome

Title	Event-free Survival (EFS)
Description	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.
Time Frame	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

Outcome Measure Data

Analysis Population Description

The intent-to-treat (ITT) population was defined as all participants who were randomized, independent of whether they received study treatment or not. Includes participants who died and participants who were censored

Arm/Group Title	Azacitidine (AZA)	Conventional Care Regimens (CCR)
Arm/Group Description	Azacitidine 75 mg/m2/day by subcutaneous injection [SC] for 7 days every 28 days, with a 21 day rest period (optimally for at least 6 cycles) plus best supportive care as needed, including antibiotics and blood product transfusions, growth factors, per physician's discretion.	CCRs included: #1 Intensive Chemotherapy: Cytarabine 100-200 mg/m^2 as a continuous intravenous infusion (CIVI) for 7 days and daunorubicin 45 to 60 mg/m^² daily (QD) IV on Days 1, 2 and 3 or Idarubicin 9-12 mg/m^² IV QD for 3 days. Consolidation Therapy (Cycle 2 and 3) = Cytarabine 100-200 mg/m^2 as a CIVI for 3 to 7 days and daunorubicin 45 to 60 mg/m^² QD or Idarubicin 9-12 mg/m^² IV QD on Days 1 and 2. The first consolidation therapy started between Day 28 and Day 70 from start of induction therapy, upon recovery of absolute neutrophil count (ANC) above 1.0 x 10^9/L and platelets above 75 x 10^9/L. The second cycle started between Day 28 and Day 70 from start of first consolidation therapy. Best supportive care (BSC) of antibiotics and transfusions, were given as needed # 2 Low-dose cytarabine 20 mg subcutaneously twice a day (BID) for 10 days every 28 days, plus BSC # 3 BSC only = transfusion of blood products, antibiotics, antifungals and nutritional help
Measure Participants	241	247
Median (95% Confidence Interval) [months]	6.7	4.8

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Azacitidine (AZA), Conventional Care Regimens (CCR)
	Comments	Median is estimated from a Kaplan-Meier distribution of EFS
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1495
	Comments
	Method	Log Rank
	Comments	2 sided unstratified
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.87
	Confidence Interval	(2-Sided) 95%; 0.72 to 1.05
	Parameter Dispersion	Type: Value:
	Estimation Comments	The hazard ratio is from an unstratified Cox proportional hazards model.

4. Secondary Outcome

Title	Relapse-Free Survival (RFS) for Participants Who Achieved a Complete Remission (CR) or Complete Remission With Incomplete Blood Count Recovery (CRi)
Description	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.
Time Frame	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

Outcome Measure Data

Analysis Population Description

Participants who achieved a CR or CRi

Arm/Group Title	Azacitidine (AZA)	Conventional Care Regimen
Arm/Group Description	Azacitidine 75 mg/m2/day by subcutaneous injection [SC] for 7 days every 28 days, with a 21 day rest period (optimally for at least 6 cycles) plus best supportive care as needed, including antibiotics and blood product transfusions, growth factors, per physician's discretion.	CCRs included: #1 Intensive Chemotherapy: Cytarabine 100-200 mg/m^2 as a continuous intravenous infusion (CIVI) for 7 days and daunorubicin 45 to 60 mg/m^² daily (QD) IV on Days 1, 2 and 3 or Idarubicin 9-12 mg/m^² IV QD for 3 days. Consolidation Therapy (Cycle 2 and 3) = Cytarabine 100-200 mg/m^2 as a CIVI for 3 to 7 days and daunorubicin 45 to 60 mg/m^² QD or Idarubicin 9-12 mg/m^² IV QD on Days 1 and 2. The first consolidation therapy started between Day 28 and Day 70 from start of induction therapy, upon recovery of absolute neutrophil count (ANC) above 1.0 x 10^9/L and platelets above 75 x 10^9/L. The second cycle started between Day 28 and Day 70 from start of first consolidation therapy. Best supportive care (BSC) of antibiotics and transfusions, were given as needed # 2 Low-dose cytarabine 20 mg subcutaneously twice a day (BID) for 10 days every 28 days, plus BSC # 3 BSC only = transfusion of blood products, antibiotics, antifungals and nutritional help
Measure Participants	67	62
Median (95% Confidence Interval) [months]	9.3	10.5

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Azacitidine (AZA), Conventional Care Regimens (CCR)
	Comments	Median is estimated from a Kaplan-Meier distribution of RFS
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.5832
	Comments
	Method	Log Rank
	Comments	2 sided unstratified
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.11
	Confidence Interval	(2-Sided) 95%; 0.75 to 1.66
	Parameter Dispersion	Type: Value:
	Estimation Comments	The hazard ratio is from an unstratified Cox proportional hazards model.

5. Secondary Outcome

Title	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)
Description	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.
Time Frame	Day 1 (randomization) to 40 months

Outcome Measure Data

Analysis Population Description

The intent-to-treat (ITT) population was defined as all participants who were randomized, independent of whether they received study treatment or not. Includes participants who died and participants who were censored

Arm/Group Title	Azacitidine (AZA)	Conventional Care Regimens (CCR)
Arm/Group Description	Azacitidine 75 mg/m2/day by subcutaneous injection [SC] for 7 days every 28 days, with a 21 day rest period (optimally for at least 6 cycles) plus best supportive care as needed, including antibiotics and blood product transfusions, growth factors, per physician's discretion.	CCRs included: #1 Intensive Chemotherapy: Cytarabine 100-200 mg/m^2 as a continuous intravenous infusion (CIVI) for 7 days and daunorubicin 45 to 60 mg/m^² daily (QD) IV on Days 1, 2 and 3 or Idarubicin 9-12 mg/m^² IV QD for 3 days. Consolidation Therapy (Cycle 2 and 3) = Cytarabine 100-200 mg/m^2 as a CIVI for 3 to 7 days and daunorubicin 45 to 60 mg/m^² QD or Idarubicin 9-12 mg/m^² IV QD on Days 1 and 2. The first consolidation therapy started between Day 28 and Day 70 from start of induction therapy, upon recovery of absolute neutrophil count (ANC) above 1.0 x 10^9/L and platelets above 75 x 10^9/L. The second cycle started between Day 28 and Day 70 from start of first consolidation therapy. Best supportive care (BSC) of antibiotics and transfusions, were given as needed # 2 Low-dose cytarabine 20 mg subcutaneously twice a day (BID) for 10 days every 28 days, plus BSC # 3 BSC only = transfusion of blood products, antibiotics, antifungals and nutritional help
Measure Participants	241	247
Number [percentage of participants]	27.8 11.5%	25.1 10.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Azacitidine (AZA), Conventional Care Regimens (CCR)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.5384
	Comments
	Method	Fisher Exact
	Comments	P-value is from Fishers exact test

6. Secondary Outcome

Title	Duration of Remission Assessed by the IRC Based on Kaplan-Meier Estimates
Description	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.
Time Frame	Day 1 (randomization) to 40 months; date of the first documented CR or CRi until date of first documented relapse.

Outcome Measure Data

Analysis Population Description

Includes those who achieved a CR or CRi and assessed by the IRC; numbers of ITT participants in each treatment group

Arm/Group Title	Azacitidine (AZA)	Conventional Care Regimen
Arm/Group Description	Azacitidine 75 mg/m2/day by subcutaneous injection [SC] for 7 days every 28 days, with a 21 day rest period (optimally for at least 6 cycles) plus best supportive care as needed, including antibiotics and blood product transfusions, growth factors, per physician's discretion.	CCRs included: #1 Intensive Chemotherapy: Cytarabine 100-200 mg/m^2 as a continuous intravenous infusion (CIVI) for 7 days and daunorubicin 45 to 60 mg/m^² daily (QD) IV on Days 1, 2 and 3 or Idarubicin 9-12 mg/m^² IV QD for 3 days. Consolidation Therapy (Cycle 2 and 3) = Cytarabine 100-200 mg/m^2 as a CIVI for 3 to 7 days and daunorubicin 45 to 60 mg/m^² QD or Idarubicin 9-12 mg/m^² IV QD on Days 1 and 2. The first consolidation therapy started between Day 28 and Day 70 from start of induction therapy, upon recovery of absolute neutrophil count (ANC) above 1.0 x 10^9/L and platelets above 75 x 10^9/L. The second cycle started between Day 28 and Day 70 from start of first consolidation therapy. Best supportive care (BSC) of antibiotics and transfusions, were given as needed # 2 Low-dose cytarabine 20 mg subcutaneously twice a day (BID) for 10 days every 28 days, plus BSC # 3 BSC only = transfusion of blood products, antibiotics, antifungals and nutritional help
Measure Participants	67	62
Median (95% Confidence Interval) [months]	10.4	12.3

7. Secondary Outcome

Title	Number of Participants Who Achieved a Cytogenetic Complete Response (CRc-10) as Determined by the IRC.
Description	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
Time Frame	Day 1 (randomization) to 40 months

Outcome Measure Data

Analysis Population Description

The intent-to-treat (ITT) population was defined as all participants who were randomized, independent of whether they received study treatment or not. Includes participants who died and participants who were censored

Arm/Group Title	Azacitidine (AZA)	Conventional Care Regimens (CCR)
Arm/Group Description	Azacitidine 75 mg/m2/day by subcutaneous injection [SC] for 7 days every 28 days, with a 21 day rest period (optimally for at least 6 cycles) plus best supportive care as needed, including antibiotics and blood product transfusions, growth factors, per physician's discretion.	CCRs included: #1 Intensive Chemotherapy: Cytarabine 100-200 mg/m^2 as a continuous intravenous infusion (CIVI) for 7 days and daunorubicin 45 to 60 mg/m^² daily (QD) IV on Days 1, 2 and 3 or Idarubicin 9-12 mg/m^² IV QD for 3 days. Consolidation Therapy (Cycle 2 and 3) = Cytarabine 100-200 mg/m^2 as a CIVI for 3 to 7 days and daunorubicin 45 to 60 mg/m^² QD or Idarubicin 9-12 mg/m^² IV QD on Days 1 and 2. The first consolidation therapy started between Day 28 and Day 70 from start of induction therapy, upon recovery of absolute neutrophil count (ANC) above 1.0 x 10^9/L and platelets above 75 x 10^9/L. The second cycle started between Day 28 and Day 70 from start of first consolidation therapy. Best supportive care (BSC) of antibiotics and transfusions, were given as needed # 2 Low-dose cytarabine 20 mg subcutaneously twice a day (BID) for 10 days every 28 days, plus BSC # 3 BSC only = transfusion of blood products, antibiotics, antifungals and nutritional help
Measure Participants	241	247
Number [participants]	5 2.1%	15 6.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Azacitidine (AZA), Conventional Care Regimens (CCR)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0376
	Comments
	Method	Fisher Exact
	Comments	P-value is from Fishers exact test

8. Secondary Outcome

Title	Number of Participants With Adverse Events (AEs)
Description	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
Time Frame	Day 1 (randomization) up to last visit completed; final data cut off of 28 Feb 2017

Outcome Measure Data

Analysis Population Description

Safety population = all randomized participants who received at least 1 dose of study drug and had 1 post-dose safety assessment. Because the BSC only regimen consisted of blood products or antibiotics given as needed, those assigned to BSC only were included in the safety population if they had at least 1 post-randomization safety assessment.

Arm/Group Title	Azacitidine (AZA)	Conventional Care Regimen #3 Best Supportive Care Only	Conventional Care Regimen #2 Low-dose Cytarabine	Conventional Care Regimen #1 Intensive Chemotherapy
Arm/Group Description	Azacitidine 75 mg/m2/day by subcutaneous injection [SC] for 7 days every 28 days, with a 21 day rest period (optimally for at least 6 cycles) plus best supportive care as needed, including antibiotics and blood product transfusions, growth factors, per physician's discretion.	Best supportive care included red blood cell (RBC) or whole blood transfusions, fresh frozen plasma transfusions, platelet transfusions, antibiotic and/or antifungal therapy, and nutritional support.	Low-dose cytarabine 20 mg SC injection twice a day (BID) for 10 days, every 28 days (optimally for at least 4 cycles) until the end of the study, unless participants were discontinued from the treatment. Best supportive care as needed, including antibiotics and transfusions, per physicians discretion.	Induction Therapy included Cytarabine 100-200 mg/m^2 as a continuous intravenous infusion (IV) for 7 days plus daunorubicin 45 to 60 mg/m^² daily IV on Days 1, 2 and 3 or Idarubicin 9-12 mg/m^² IV daily for 3 days as an alternative to daunorubicin (Cycle 1). Consolidation Therapy (Cycle 2 and 3) Cytarabine 100-200 mg/m^2 as a continuous IV infusion for a total of 3 to 7 days plus daunorubicin 45 to 60 mg/m^² daily or Idarubicin 9-12 mg/m^² IV daily on Days 1 and 2. The first consolidation therapy started between Day 28 and Day 70 from commencement of induction therapy, upon recovery of absolute neutrophil count (ANC) to at least 1.0 x 10^9/L and platelets to at least 75 x 10^9/L. The second consolidation cycle, if given, started between Day 28 and Day 70 from commencement of the first consolidation therapy. Participants could receive BSC as needed, including antibiotics and transfusions, physicians discretion.
Measure Participants	236	40	153	42
At least one Treatment Emergent AE	234 97.1%	36 14.6%	153 31.4%	42 NaN
At least one TEAE related to study drug	188 78%	0 0%	124 25.4%	39 NaN
Grade 3-4 adverse event	207 85.9%	26 10.5%	141 28.9%	37 NaN
Grade 3-4 adverse event related to any study drug	125 51.9%	0 0%	90 18.4%	29 NaN
At least one Grade 5 (leading to death) TEAE	56 23.2%	23 9.3%	38 7.8%	9 NaN
Grade 5 adverse event related to any study drug	12 5%	0 0%	10 2%	4 NaN
Serious TEAE	188 78%	30 12.1%	118 24.2%	27 NaN
Serious TEAE related to any study drug	87 36.1%	0 0%	56 11.5%	14 NaN
TEAE leading to discontinuation of study drug	110 45.6%	0 0%	68 13.9%	11 NaN
Study drug-related TEAE leading to discontinuation	22 9.1%	0 0%	20 4.1%	5 NaN
TEAE leading to study drug dose reduction	8 3.3%	0 0%	2 0.4%	2 NaN
TEAE leading to study drug dose interruption	116 48.1%	0 0%	61 12.5%	4 NaN
TEAE causing study drug dose reduction/disruption	13 5.4%	0 0%	7 1.4%	0 NaN

9. Secondary Outcome

Title	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
Description	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).
Time Frame	Baseline to Cycle 3; at approximately 3 months

Outcome Measure Data

Analysis Population Description

The HRQoL Evaluable population included only participants with a baseline QoL assessment and at least 1 follow-up assessment. Time windows were applied post-hoc to increase the size of the analyzable population.

Arm/Group Title	Azacitidine (AZA)	Conventional Care Regimens (CCR)
Arm/Group Description	Azacitidine 75 mg/m2/day by subcutaneous injection [SC] for 7 days every 28 days, with a 21 day rest period (optimally for at least 6 cycles) plus best supportive care as needed, including antibiotics and blood product transfusions, growth factors, per physician's discretion.	CCRs included: #1 Intensive Chemotherapy: Cytarabine 100-200 mg/m^2 as a continuous intravenous infusion (CIVI) for 7 days and daunorubicin 45 to 60 mg/m^² daily (QD) IV on Days 1, 2 and 3 or Idarubicin 9-12 mg/m^² IV QD for 3 days. Consolidation Therapy (Cycle 2 and 3) = Cytarabine 100-200 mg/m^2 as a CIVI for 3 to 7 days and daunorubicin 45 to 60 mg/m^² QD or Idarubicin 9-12 mg/m^² IV QD on Days 1 and 2. The first consolidation therapy started between Day 28 and Day 70 from start of induction therapy, upon recovery of absolute neutrophil count (ANC) above 1.0 x 10^9/L and platelets above 75 x 10^9/L. The second cycle started between Day 28 and Day 70 from start of first consolidation therapy. Best supportive care (BSC) of antibiotics and transfusions, were given as needed # 2 Low-dose cytarabine 20 mg subcutaneously twice a day (BID) for 10 days every 28 days, plus BSC # 3 BSC only = transfusion of blood products, antibiotics, antifungals and nutritional help
Measure Participants	135	101
Mean (Standard Deviation) [units on a scale]	-1.5 (24.69)	-1.9 (27.54)

10. Secondary Outcome

Title	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
Description	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).
Time Frame	Baseline to Cycle 5, at approximately 5 months

Outcome Measure Data

Analysis Population Description

The HRQoL Evaluable population included only participants with a baseline QoL assessment and at least 1 follow-up assessment. Time windows were applied post-hoc to increase the size of the analyzable population.

Arm/Group Title	Azacitidine (AZA)	Conventional Care Regimens (CCR)
Arm/Group Description	Azacitidine 75 mg/m2/day by subcutaneous injection [SC] for 7 days every 28 days, with a 21 day rest period (optimally for at least 6 cycles) plus best supportive care as needed, including antibiotics and blood product transfusions, growth factors, per physician's discretion.	CCRs included: #1 Intensive Chemotherapy: Cytarabine 100-200 mg/m^2 as a continuous intravenous infusion (CIVI) for 7 days and daunorubicin 45 to 60 mg/m^² daily (QD) IV on Days 1, 2 and 3 or Idarubicin 9-12 mg/m^² IV QD for 3 days. Consolidation Therapy (Cycle 2 and 3) = Cytarabine 100-200 mg/m^2 as a CIVI for 3 to 7 days and daunorubicin 45 to 60 mg/m^² QD or Idarubicin 9-12 mg/m^² IV QD on Days 1 and 2. The first consolidation therapy started between Day 28 and Day 70 from start of induction therapy, upon recovery of absolute neutrophil count (ANC) above 1.0 x 10^9/L and platelets above 75 x 10^9/L. The second cycle started between Day 28 and Day 70 from start of first consolidation therapy. Best supportive care (BSC) of antibiotics and transfusions, were given as needed # 2 Low-dose cytarabine 20 mg subcutaneously twice a day (BID) for 10 days every 28 days, plus BSC # 3 BSC only = transfusion of blood products, antibiotics, antifungals and nutritional help
Measure Participants	112	66
Mean (Standard Deviation) [units on a scale]	-2.8 (27.36)	-7.1 (27.61)

11. Secondary Outcome

Title	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
Description	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).
Time Frame	Baseline to Cycle 7, at approximately 7 months

Outcome Measure Data

Analysis Population Description

The HRQoL Evaluable population included only participants with a baseline QoL assessment and at least 1 follow-up assessment. Time windows were applied post-hoc to increase the size of the analyzable population.

Arm/Group Title	Azacitidine (AZA)	Conventional Care Regimens (CCR)
Arm/Group Description	Azacitidine 75 mg/m2/day by subcutaneous injection [SC] for 7 days every 28 days, with a 21 day rest period (optimally for at least 6 cycles) plus best supportive care as needed, including antibiotics and blood product transfusions, growth factors, per physician's discretion.	CCRs included: #1 Intensive Chemotherapy: Cytarabine 100-200 mg/m^2 as a continuous intravenous infusion (CIVI) for 7 days and daunorubicin 45 to 60 mg/m^² daily (QD) IV on Days 1, 2 and 3 or Idarubicin 9-12 mg/m^² IV QD for 3 days. Consolidation Therapy (Cycle 2 and 3) = Cytarabine 100-200 mg/m^2 as a CIVI for 3 to 7 days and daunorubicin 45 to 60 mg/m^² QD or Idarubicin 9-12 mg/m^² IV QD on Days 1 and 2. The first consolidation therapy started between Day 28 and Day 70 from start of induction therapy, upon recovery of absolute neutrophil count (ANC) above 1.0 x 10^9/L and platelets above 75 x 10^9/L. The second cycle started between Day 28 and Day 70 from start of first consolidation therapy. Best supportive care (BSC) of antibiotics and transfusions, were given as needed # 2 Low-dose cytarabine 20 mg subcutaneously twice a day (BID) for 10 days every 28 days, plus BSC # 3 BSC only = transfusion of blood products, antibiotics, antifungals and nutritional help
Measure Participants	94	53
Mean (Standard Deviation) [units on a scale]	-6.1 (26.90)	-12.2 (30.45)

12. Secondary Outcome

Title	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
Description	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).
Time Frame	Baseline to Cycle 9, at approximately 9 months

Outcome Measure Data

Analysis Population Description

The HRQoL Evaluable population included only participants with a baseline QoL assessment and at least 1 follow-up assessment. Time windows were applied post-hoc to increase the size of the analyzable population. .

Arm/Group Title	Azacitidine (AZA)	Conventional Care Regimens (CCR)
Arm/Group Description	Azacitidine 75 mg/m2/day by subcutaneous injection [SC] for 7 days every 28 days, with a 21 day rest period (optimally for at least 6 cycles) plus best supportive care as needed, including antibiotics and blood product transfusions, growth factors, per physician's discretion.	CCRs included: #1 Intensive Chemotherapy: Cytarabine 100-200 mg/m^2 as a continuous intravenous infusion (CIVI) for 7 days and daunorubicin 45 to 60 mg/m^² daily (QD) IV on Days 1, 2 and 3 or Idarubicin 9-12 mg/m^² IV QD for 3 days. Consolidation Therapy (Cycle 2 and 3) = Cytarabine 100-200 mg/m^2 as a CIVI for 3 to 7 days and daunorubicin 45 to 60 mg/m^² QD or Idarubicin 9-12 mg/m^² IV QD on Days 1 and 2. The first consolidation therapy started between Day 28 and Day 70 from start of induction therapy, upon recovery of absolute neutrophil count (ANC) above 1.0 x 10^9/L and platelets above 75 x 10^9/L. The second cycle started between Day 28 and Day 70 from start of first consolidation therapy. Best supportive care (BSC) of antibiotics and transfusions, were given as needed # 2 Low-dose cytarabine 20 mg subcutaneously twice a day (BID) for 10 days every 28 days, plus BSC # 3 BSC only = transfusion of blood products, antibiotics, antifungals and nutritional help
Measure Participants	80	36
Mean (Standard Deviation) [units on a scale]	-9.0 (27.90)	-10.2 (33.85)

13. Secondary Outcome

Title	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
Description	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).
Time Frame	Baseline to End of Study; at approximately 11-12 months

Outcome Measure Data

Analysis Population Description

The HRQoL Evaluable population included only participants with a baseline QoL assessment and at least 1 follow-up assessment. Time windows were applied post-hoc to increase the size of the analyzable population.

Arm/Group Title	Azacitidine (AZA)	Conventional Care Regimens (CCR)
Arm/Group Description	Azacitidine 75 mg/m2/day by subcutaneous injection [SC] for 7 days every 28 days, with a 21 day rest period (optimally for at least 6 cycles) plus best supportive care as needed, including antibiotics and blood product transfusions, growth factors, per physician's discretion.	CCRs included: #1 Intensive Chemotherapy: Cytarabine 100-200 mg/m^2 as a continuous intravenous infusion (CIVI) for 7 days and daunorubicin 45 to 60 mg/m^² daily (QD) IV on Days 1, 2 and 3 or Idarubicin 9-12 mg/m^² IV QD for 3 days. Consolidation Therapy (Cycle 2 and 3) = Cytarabine 100-200 mg/m^2 as a CIVI for 3 to 7 days and daunorubicin 45 to 60 mg/m^² QD or Idarubicin 9-12 mg/m^² IV QD on Days 1 and 2. The first consolidation therapy started between Day 28 and Day 70 from start of induction therapy, upon recovery of absolute neutrophil count (ANC) above 1.0 x 10^9/L and platelets above 75 x 10^9/L. The second cycle started between Day 28 and Day 70 from start of first consolidation therapy. Best supportive care (BSC) of antibiotics and transfusions, were given as needed # 2 Low-dose cytarabine 20 mg subcutaneously twice a day (BID) for 10 days every 28 days, plus BSC # 3 BSC only = transfusion of blood products, antibiotics, antifungals and nutritional help
Measure Participants	87	80
Mean (Standard Deviation) [units on a scale]	8.9 (33.54)	6.1 (34.19)

14. Secondary Outcome

Title	HRQoL: Change From Baseline in the EORTC QLQ-C30 Dyspnea
Description	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).
Time Frame	Baseline to Cycle 3, at approximately 3 months

Outcome Measure Data

Analysis Population Description

The HRQoL Evaluable population included only participants with a baseline QoL assessment and at least 1 follow-up assessment. Time windows were applied post-hoc to increase the size of the analyzable population.

Arm/Group Title	Azacitidine (AZA)	Conventional Care Regimen
Arm/Group Description	Azacitidine 75 mg/m2/day by subcutaneous injection [SC] for 7 days every 28 days, with a 21 day rest period (optimally for at least 6 cycles) plus best supportive care as needed, including antibiotics and blood product transfusions, growth factors, per physician's discretion.	CCRs included: #1 Intensive Chemotherapy: Cytarabine 100-200 mg/m^2 as a continuous intravenous infusion (CIVI) for 7 days and daunorubicin 45 to 60 mg/m^² daily (QD) IV on Days 1, 2 and 3 or Idarubicin 9-12 mg/m^² IV QD for 3 days. Consolidation Therapy (Cycle 2 and 3) = Cytarabine 100-200 mg/m^2 as a CIVI for 3 to 7 days and daunorubicin 45 to 60 mg/m^² QD or Idarubicin 9-12 mg/m^² IV QD on Days 1 and 2. The first consolidation therapy started between Day 28 and Day 70 from start of induction therapy, upon recovery of absolute neutrophil count (ANC) above 1.0 x 10^9/L and platelets above 75 x 10^9/L. The second cycle started between Day 28 and Day 70 from start of first consolidation therapy. Best supportive care (BSC) of antibiotics and transfusions, were given as needed # 2 Low-dose cytarabine 20 mg subcutaneously twice a day (BID) for 10 days every 28 days, plus BSC # 3 BSC only = transfusion of blood products, antibiotics, antifungals and nutritional help
Measure Participants	136	101
Mean (Standard Deviation) [units on a scale]	5.1 (26.88)	-1.7 (30.69)

15. Secondary Outcome

Title	HRQoL: Change From Baseline in the EORTC QLQ-C30 Dyspnea
Description	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).
Time Frame	Baseline to Cycle 5, at approximately 5 months

Outcome Measure Data

Analysis Population Description

The HRQoL Evaluable population included only participants with a baseline QoL assessment and at least 1 follow-up assessment. Time windows were applied post-hoc to increase the size of the analyzable population.

Arm/Group Title	Azacitidine (AZA)	Conventional Care Regimen
Arm/Group Description	Azacitidine 75 mg/m2/day by subcutaneous injection [SC] for 7 days every 28 days, with a 21 day rest period (optimally for at least 6 cycles) plus best supportive care as needed, including antibiotics and blood product transfusions, growth factors, per physician's discretion.	CCRs included: #1 Intensive Chemotherapy: Cytarabine 100-200 mg/m^2 as a continuous intravenous infusion (CIVI) for 7 days and daunorubicin 45 to 60 mg/m^² daily (QD) IV on Days 1, 2 and 3 or Idarubicin 9-12 mg/m^² IV QD for 3 days. Consolidation Therapy (Cycle 2 and 3) = Cytarabine 100-200 mg/m^2 as a CIVI for 3 to 7 days and daunorubicin 45 to 60 mg/m^² QD or Idarubicin 9-12 mg/m^² IV QD on Days 1 and 2. The first consolidation therapy started between Day 28 and Day 70 from start of induction therapy, upon recovery of absolute neutrophil count (ANC) above 1.0 x 10^9/L and platelets above 75 x 10^9/L. The second cycle started between Day 28 and Day 70 from start of first consolidation therapy. Best supportive care (BSC) of antibiotics and transfusions, were given as needed # 2 Low-dose cytarabine 20 mg subcutaneously twice a day (BID) for 10 days every 28 days, plus BSC # 3 BSC only = transfusion of blood products, antibiotics, antifungals and nutritional help
Measure Participants	112	66
Mean (Standard Deviation) [units on a scale]	3.9 (27.49)	-6.6 (28.18)

16. Secondary Outcome

Title	HRQoL: Change From Baseline in the EORTC QLQ-C30 Dyspnea
Description	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).
Time Frame	Baseline to Cycle 7, at approximately 7 months

Outcome Measure Data

Analysis Population Description

The HRQoL Evaluable population included only participants with a baseline QoL assessment and at least 1 follow-up assessment. Time windows were applied post-hoc to increase the size of the analyzable population.

Arm/Group Title	Azacitidine (AZA)	Conventional Care Regimen
Arm/Group Description	Azacitidine 75 mg/m2/day by subcutaneous injection [SC] for 7 days every 28 days, with a 21 day rest period (optimally for at least 6 cycles) plus best supportive care as needed, including antibiotics and blood product transfusions, growth factors, per physician's discretion.	CCRs included: #1 Intensive Chemotherapy: Cytarabine 100-200 mg/m^2 as a continuous intravenous infusion (CIVI) for 7 days and daunorubicin 45 to 60 mg/m^² daily (QD) IV on Days 1, 2 and 3 or Idarubicin 9-12 mg/m^² IV QD for 3 days. Consolidation Therapy (Cycle 2 and 3) = Cytarabine 100-200 mg/m^2 as a CIVI for 3 to 7 days and daunorubicin 45 to 60 mg/m^² QD or Idarubicin 9-12 mg/m^² IV QD on Days 1 and 2. The first consolidation therapy started between Day 28 and Day 70 from start of induction therapy, upon recovery of absolute neutrophil count (ANC) above 1.0 x 10^9/L and platelets above 75 x 10^9/L. The second cycle started between Day 28 and Day 70 from start of first consolidation therapy. Best supportive care (BSC) of antibiotics and transfusions, were given as needed # 2 Low-dose cytarabine 20 mg subcutaneously twice a day (BID) for 10 days every 28 days, plus BSC # 3 BSC only = transfusion of blood products, antibiotics, antifungals and nutritional help
Measure Participants	94	53
Mean (Standard Deviation) [units on a scale]	0.4 (29.93)	-8.8 (28.61)

17. Secondary Outcome

Title	HRQoL: Change From Baseline in the EORTC QLQ-C30 Dyspnea
Description	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).
Time Frame	Baseline to Cycle 9, at approximately 9 months

Outcome Measure Data

Analysis Population Description

The HRQoL Evaluable population included only participants with a baseline QoL assessment and at least 1 follow-up assessment. Time windows were applied post-hoc to increase the size of the analyzable population. The analysis included 157 from the azacitidine group and 134 in the CCR group, a smaller number than the ITT population.

Arm/Group Title	Azacitidine (AZA)	Conventional Care Regimen
Arm/Group Description	Azacitidine 75 mg/m2/day by subcutaneous injection [SC] for 7 days every 28 days, with a 21 day rest period (optimally for at least 6 cycles) plus best supportive care as needed, including antibiotics and blood product transfusions, growth factors, per physician's discretion.	CCRs included: #1 Intensive Chemotherapy: Cytarabine 100-200 mg/m^2 as a continuous intravenous infusion (CIVI) for 7 days and daunorubicin 45 to 60 mg/m^² daily (QD) IV on Days 1, 2 and 3 or Idarubicin 9-12 mg/m^² IV QD for 3 days. Consolidation Therapy (Cycle 2 and 3) = Cytarabine 100-200 mg/m^2 as a CIVI for 3 to 7 days and daunorubicin 45 to 60 mg/m^² QD or Idarubicin 9-12 mg/m^² IV QD on Days 1 and 2. The first consolidation therapy started between Day 28 and Day 70 from start of induction therapy, upon recovery of absolute neutrophil count (ANC) above 1.0 x 10^9/L and platelets above 75 x 10^9/L. The second cycle started between Day 28 and Day 70 from start of first consolidation therapy. Best supportive care (BSC) of antibiotics and transfusions, were given as needed # 2 Low-dose cytarabine 20 mg subcutaneously twice a day (BID) for 10 days every 28 days, plus BSC # 3 BSC only = transfusion of blood products, antibiotics, antifungals and nutritional help
Measure Participants	81	36
Mean (Standard Deviation) [units on a scale]	-4.9 (26.93)	-2.8 (26.87)

18. Secondary Outcome

Title	HRQoL: Change From Baseline in the EORTC QLQ-C30 Dyspnea
Description	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).
Time Frame	Baseline to end of study, at approximately 11-12 months

Outcome Measure Data

Analysis Population Description

The HRQoL Evaluable population included only participants with a baseline QoL assessment and at least 1 follow-up assessment. Time windows were applied post-hoc to increase the size of the analyzable population.

Arm/Group Title	Azacitidine (AZA)	Conventional Care Regimen
Arm/Group Description	Azacitidine 75 mg/m2/day by subcutaneous injection [SC] for 7 days every 28 days, with a 21 day rest period (optimally for at least 6 cycles) plus best supportive care as needed, including antibiotics and blood product transfusions, growth factors, per physician's discretion.	CCRs included: #1 Intensive Chemotherapy: Cytarabine 100-200 mg/m^2 as a continuous intravenous infusion (CIVI) for 7 days and daunorubicin 45 to 60 mg/m^² daily (QD) IV on Days 1, 2 and 3 or Idarubicin 9-12 mg/m^² IV QD for 3 days. Consolidation Therapy (Cycle 2 and 3) = Cytarabine 100-200 mg/m^2 as a CIVI for 3 to 7 days and daunorubicin 45 to 60 mg/m^² QD or Idarubicin 9-12 mg/m^² IV QD on Days 1 and 2. The first consolidation therapy started between Day 28 and Day 70 from start of induction therapy, upon recovery of absolute neutrophil count (ANC) above 1.0 x 10^9/L and platelets above 75 x 10^9/L. The second cycle started between Day 28 and Day 70 from start of first consolidation therapy. Best supportive care (BSC) of antibiotics and transfusions, were given as needed # 2 Low-dose cytarabine 20 mg subcutaneously twice a day (BID) for 10 days every 28 days, plus BSC # 3 BSC only = transfusion of blood products, antibiotics, antifungals and nutritional help
Measure Participants	87	80
Mean (Standard Deviation) [units on a scale]	12.6 (31.43)	6.3 (35.22)

19. Secondary Outcome

Title	HRQoL: Change From Baseline in the EORTC QLQ-C30 Physical Functioning Domain
Description	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.
Time Frame	Baseline to Cycle 3, at approximately 3 months

Outcome Measure Data

Analysis Population Description

The HRQoL Evaluable population included only participants with a baseline QoL assessment and at least 1 follow-up assessment. Time windows were applied post-hoc to increase the size of the analyzable population.

Arm/Group Title	Azacitidine (AZA)	Conventional Care Regimen
Arm/Group Description	Azacitidine 75 mg/m2/day by subcutaneous injection [SC] for 7 days every 28 days, with a 21 day rest period (optimally for at least 6 cycles) plus best supportive care as needed, including antibiotics and blood product transfusions, growth factors, per physician's discretion.	CCRs included: #1 Intensive Chemotherapy: Cytarabine 100-200 mg/m^2 as a continuous intravenous infusion (CIVI) for 7 days and daunorubicin 45 to 60 mg/m^² daily (QD) IV on Days 1, 2 and 3 or Idarubicin 9-12 mg/m^² IV QD for 3 days. Consolidation Therapy (Cycle 2 and 3) = Cytarabine 100-200 mg/m^2 as a CIVI for 3 to 7 days and daunorubicin 45 to 60 mg/m^² QD or Idarubicin 9-12 mg/m^² IV QD on Days 1 and 2. The first consolidation therapy started between Day 28 and Day 70 from start of induction therapy, upon recovery of absolute neutrophil count (ANC) above 1.0 x 10^9/L and platelets above 75 x 10^9/L. The second cycle started between Day 28 and Day 70 from start of first consolidation therapy. Best supportive care (BSC) of antibiotics and transfusions, were given as needed # 2 Low-dose cytarabine 20 mg subcutaneously twice a day (BID) for 10 days every 28 days, plus BSC # 3 BSC only = transfusion of blood products, antibiotics, antifungals and nutritional help
Measure Participants	136	102
Mean (Standard Deviation) [units on a scale]	-4.2 (17.98)	-0.3 (18.85)

20. Secondary Outcome

Title	HRQoL: Change From Baseline in the EORTC QLQ-C30 Physical Functioning Domain
Description	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.
Time Frame	Baseline to Cycle 5, at approximately 5 months

Outcome Measure Data

Analysis Population Description

The HRQoL Evaluable population included only participants with a baseline QoL assessment and at least 1 follow-up assessment. Time windows were applied post-hoc to increase the size of the analyzable population.

Arm/Group Title	Azacitidine (AZA)	Conventional Care Regimen
Arm/Group Description	Azacitidine 75 mg/m2/day by subcutaneous injection [SC] for 7 days every 28 days, with a 21 day rest period (optimally for at least 6 cycles) plus best supportive care as needed, including antibiotics and blood product transfusions, growth factors, per physician's discretion.	CCRs included: #1 Intensive Chemotherapy: Cytarabine 100-200 mg/m^2 as a continuous intravenous infusion (CIVI) for 7 days and daunorubicin 45 to 60 mg/m^² daily (QD) IV on Days 1, 2 and 3 or Idarubicin 9-12 mg/m^² IV QD for 3 days. Consolidation Therapy (Cycle 2 and 3) = Cytarabine 100-200 mg/m^2 as a CIVI for 3 to 7 days and daunorubicin 45 to 60 mg/m^² QD or Idarubicin 9-12 mg/m^² IV QD on Days 1 and 2. The first consolidation therapy started between Day 28 and Day 70 from start of induction therapy, upon recovery of absolute neutrophil count (ANC) above 1.0 x 10^9/L and platelets above 75 x 10^9/L. The second cycle started between Day 28 and Day 70 from start of first consolidation therapy. Best supportive care (BSC) of antibiotics and transfusions, were given as needed # 2 Low-dose cytarabine 20 mg subcutaneously twice a day (BID) for 10 days every 28 days, plus BSC # 3 BSC only = transfusion of blood products, antibiotics, antifungals and nutritional help
Measure Participants	112	67
Mean (Standard Deviation) [units on a scale]	-4.4 (19.25)	-1.3 (20.41)

21. Secondary Outcome

Title	HRQoL: Change From Baseline in the EORTC QLQ-C30 Physical Functioning Domain
Description	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.
Time Frame	Baseline to Cycle 7, at approximately 7 months

Outcome Measure Data

Analysis Population Description

The HRQoL Evaluable population included only participants with a baseline QoL assessment and at least 1 follow-up assessment. Time windows were applied post-hoc to increase the size of the analyzable population.

Arm/Group Title	Azacitidine (AZA)	Conventional Care Regimen
Arm/Group Description	Azacitidine 75 mg/m2/day by subcutaneous injection [SC] for 7 days every 28 days, with a 21 day rest period (optimally for at least 6 cycles) plus best supportive care as needed, including antibiotics and blood product transfusions, growth factors, per physician's discretion.	CCRs included: #1 Intensive Chemotherapy: Cytarabine 100-200 mg/m^2 as a continuous intravenous infusion (CIVI) for 7 days and daunorubicin 45 to 60 mg/m^² daily (QD) IV on Days 1, 2 and 3 or Idarubicin 9-12 mg/m^² IV QD for 3 days. Consolidation Therapy (Cycle 2 and 3) = Cytarabine 100-200 mg/m^2 as a CIVI for 3 to 7 days and daunorubicin 45 to 60 mg/m^² QD or Idarubicin 9-12 mg/m^² IV QD on Days 1 and 2. The first consolidation therapy started between Day 28 and Day 70 from start of induction therapy, upon recovery of absolute neutrophil count (ANC) above 1.0 x 10^9/L and platelets above 75 x 10^9/L. The second cycle started between Day 28 and Day 70 from start of first consolidation therapy. Best supportive care (BSC) of antibiotics and transfusions, were given as needed # 2 Low-dose cytarabine 20 mg subcutaneously twice a day (BID) for 10 days every 28 days, plus BSC # 3 BSC only = transfusion of blood products, antibiotics, antifungals and nutritional help
Measure Participants	94	54
Mean (Standard Deviation) [units on a scale]	1.6 (18.75)	1.5 (23.08)

22. Secondary Outcome

Title	HRQoL: Change From Baseline in the EORTC QLQ-C30 Physical Functioning Domain
Description	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.
Time Frame	Baseline to Cycle 9, at approximately 9 months

Outcome Measure Data

Analysis Population Description

The HRQoL Evaluable population included only participants with a baseline QoL assessment and at least 1 follow-up assessment. Time windows were applied post-hoc to increase the size of the analyzable population.

Arm/Group Title	Azacitidine (AZA)	Conventional Care Regimen
Arm/Group Description	Azacitidine 75 mg/m2/day by subcutaneous injection [SC] for 7 days every 28 days, with a 21 day rest period (optimally for at least 6 cycles) plus best supportive care as needed, including antibiotics and blood product transfusions, growth factors, per physician's discretion.	CCRs included: #1 Intensive Chemotherapy: Cytarabine 100-200 mg/m^2 as a continuous intravenous infusion (CIVI) for 7 days and daunorubicin 45 to 60 mg/m^² daily (QD) IV on Days 1, 2 and 3 or Idarubicin 9-12 mg/m^² IV QD for 3 days. Consolidation Therapy (Cycle 2 and 3) = Cytarabine 100-200 mg/m^2 as a CIVI for 3 to 7 days and daunorubicin 45 to 60 mg/m^² QD or Idarubicin 9-12 mg/m^² IV QD on Days 1 and 2. The first consolidation therapy started between Day 28 and Day 70 from start of induction therapy, upon recovery of absolute neutrophil count (ANC) above 1.0 x 10^9/L and platelets above 75 x 10^9/L. The second cycle started between Day 28 and Day 70 from start of first consolidation therapy. Best supportive care (BSC) of antibiotics and transfusions, were given as needed # 2 Low-dose cytarabine 20 mg subcutaneously twice a day (BID) for 10 days every 28 days, plus BSC # 3 BSC only = transfusion of blood products, antibiotics, antifungals and nutritional help
Measure Participants	81	36
Mean (Standard Deviation) [units on a scale]	3.5 (18.26)	-0.4 (22.81)

23. Secondary Outcome

Title	HRQoL: Change From Baseline in the EORTC QLQ-C30 Physical Functioning Domain
Description	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.
Time Frame	Baseline to end of study, at approximately 11-12 months

Outcome Measure Data

Analysis Population Description

The HRQoL Evaluable population included only participants with a baseline QoL assessment and at least 1 follow-up assessment. Time windows were applied post-hoc to increase the size of the analyzable population.

Arm/Group Title	Azacitidine (AZA)	Conventional Care Regimen
Arm/Group Description	Azacitidine 75 mg/m2/day by subcutaneous injection [SC] for 7 days every 28 days, with a 21 day rest period (optimally for at least 6 cycles) plus best supportive care as needed, including antibiotics and blood product transfusions, growth factors, per physician's discretion.	CCRs included: #1 Intensive Chemotherapy: Cytarabine 100-200 mg/m^2 as a continuous intravenous infusion (CIVI) for 7 days and daunorubicin 45 to 60 mg/m^² daily (QD) IV on Days 1, 2 and 3 or Idarubicin 9-12 mg/m^² IV QD for 3 days. Consolidation Therapy (Cycle 2 and 3) = Cytarabine 100-200 mg/m^2 as a CIVI for 3 to 7 days and daunorubicin 45 to 60 mg/m^² QD or Idarubicin 9-12 mg/m^² IV QD on Days 1 and 2. The first consolidation therapy started between Day 28 and Day 70 from start of induction therapy, upon recovery of absolute neutrophil count (ANC) above 1.0 x 10^9/L and platelets above 75 x 10^9/L. The second cycle started between Day 28 and Day 70 from start of first consolidation therapy. Best supportive care (BSC) of antibiotics and transfusions, were given as needed # 2 Low-dose cytarabine 20 mg subcutaneously twice a day (BID) for 10 days every 28 days, plus BSC # 3 BSC only = transfusion of blood products, antibiotics, antifungals and nutritional help
Measure Participants	87	81
Mean (Standard Deviation) [units on a scale]	-13.0 (26.74)	-9.4 (26.43)

24. Secondary Outcome

Title	HRQoL: Change From Baseline in the EORTC QLQ-C30 Global Health Status-/Quality of Life Domain
Description	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.
Time Frame	Baseline to Cycle 3, at approximately 3 months

Outcome Measure Data

Analysis Population Description

The HRQoL Evaluable population included only participants with a baseline QoL assessment and at least 1 follow-up assessment. Time windows were applied post-hoc to increase the size of the analyzable population.

Arm/Group Title	Azacitidine (AZA)	Conventional Care Regimen
Arm/Group Description	Azacitidine 75 mg/m2/day by subcutaneous injection [SC] for 7 days every 28 days, with a 21 day rest period (optimally for at least 6 cycles) plus best supportive care as needed, including antibiotics and blood product transfusions, growth factors, per physician's discretion.	CCRs included: #1 Intensive Chemotherapy: Cytarabine 100-200 mg/m^2 as a continuous intravenous infusion (CIVI) for 7 days and daunorubicin 45 to 60 mg/m^² daily (QD) IV on Days 1, 2 and 3 or Idarubicin 9-12 mg/m^² IV QD for 3 days. Consolidation Therapy (Cycle 2 and 3) = Cytarabine 100-200 mg/m^2 as a CIVI for 3 to 7 days and daunorubicin 45 to 60 mg/m^² QD or Idarubicin 9-12 mg/m^² IV QD on Days 1 and 2. The first consolidation therapy started between Day 28 and Day 70 from start of induction therapy, upon recovery of absolute neutrophil count (ANC) above 1.0 x 10^9/L and platelets above 75 x 10^9/L. The second cycle started between Day 28 and Day 70 from start of first consolidation therapy. Best supportive care (BSC) of antibiotics and transfusions, were given as needed # 2 Low-dose cytarabine 20 mg subcutaneously twice a day (BID) for 10 days every 28 days, plus BSC # 3 BSC only = transfusion of blood products, antibiotics, antifungals and nutritional help
Measure Participants	134	101
Mean (Standard Deviation) [units on a scale]	0.9 (20.97)	3.8 (26.42)

25. Secondary Outcome

Title	HRQoL: Change From Baseline in the EORTC QLQ-C30 Global Health Status-/Quality of Life Domain
Description	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.
Time Frame	Baseline to Cycle 5, at approximately 5 months

Outcome Measure Data

Analysis Population Description

The HRQoL Evaluable population included only participants with a baseline QoL assessment and at least 1 follow-up assessment. Time windows were applied post-hoc to increase the size of the analyzable population.

Arm/Group Title	Azacitidine (AZA)	Conventional Care Regimen
Arm/Group Description	Azacitidine 75 mg/m2/day by subcutaneous injection [SC] for 7 days every 28 days, with a 21 day rest period (optimally for at least 6 cycles) plus best supportive care as needed, including antibiotics and blood product transfusions, growth factors, per physician's discretion.	CCRs included: #1 Intensive Chemotherapy: Cytarabine 100-200 mg/m^2 as a continuous intravenous infusion (CIVI) for 7 days and daunorubicin 45 to 60 mg/m^² daily (QD) IV on Days 1, 2 and 3 or Idarubicin 9-12 mg/m^² IV QD for 3 days. Consolidation Therapy (Cycle 2 and 3) = Cytarabine 100-200 mg/m^2 as a CIVI for 3 to 7 days and daunorubicin 45 to 60 mg/m^² QD or Idarubicin 9-12 mg/m^² IV QD on Days 1 and 2. The first consolidation therapy started between Day 28 and Day 70 from start of induction therapy, upon recovery of absolute neutrophil count (ANC) above 1.0 x 10^9/L and platelets above 75 x 10^9/L. The second cycle started between Day 28 and Day 70 from start of first consolidation therapy. Best supportive care (BSC) of antibiotics and transfusions, were given as needed # 2 Low-dose cytarabine 20 mg subcutaneously twice a day (BID) for 10 days every 28 days, plus BSC # 3 BSC only = transfusion of blood products, antibiotics, antifungals and nutritional help
Measure Participants	112	66
Mean (Standard Deviation) [units on a scale]	1.6 (22.50)	9.0 (24.82)

26. Secondary Outcome

Title	HRQoL: Change From Baseline in the EORTC QLQ-C30 Global Health Status-/Quality of Life Domain
Description	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.
Time Frame	Baseline to Cycle 7, at approximately 7 months

Outcome Measure Data

Analysis Population Description

The HRQoL Evaluable population included only participants with a baseline QoL assessment and at least 1 follow-up assessment. Time windows were applied post-hoc to increase the size of the analyzable population.

Arm/Group Title	Azacitidine (AZA)	Conventional Care Regimen
Arm/Group Description	Azacitidine 75 mg/m2/day by subcutaneous injection [SC] for 7 days every 28 days, with a 21 day rest period (optimally for at least 6 cycles) plus best supportive care as needed, including antibiotics and blood product transfusions, growth factors, per physician's discretion.	CCRs included: #1 Intensive Chemotherapy: Cytarabine 100-200 mg/m^2 as a continuous intravenous infusion (CIVI) for 7 days and daunorubicin 45 to 60 mg/m^² daily (QD) IV on Days 1, 2 and 3 or Idarubicin 9-12 mg/m^² IV QD for 3 days. Consolidation Therapy (Cycle 2 and 3) = Cytarabine 100-200 mg/m^2 as a CIVI for 3 to 7 days and daunorubicin 45 to 60 mg/m^² QD or Idarubicin 9-12 mg/m^² IV QD on Days 1 and 2. The first consolidation therapy started between Day 28 and Day 70 from start of induction therapy, upon recovery of absolute neutrophil count (ANC) above 1.0 x 10^9/L and platelets above 75 x 10^9/L. The second cycle started between Day 28 and Day 70 from start of first consolidation therapy. Best supportive care (BSC) of antibiotics and transfusions, were given as needed # 2 Low-dose cytarabine 20 mg subcutaneously twice a day (BID) for 10 days every 28 days, plus BSC # 3 BSC only = transfusion of blood products, antibiotics, antifungals and nutritional help
Measure Participants	94	52
Mean (Standard Deviation) [units on a scale]	5.1 (25.84)	8.7 (27.91)

27. Secondary Outcome

Title	HRQoL: Change From Baseline in the EORTC QLQ-C30 Global Health Status-/Quality of Life Domain
Description	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.
Time Frame	Baseline to Cycle 9, at approximately 9 months

Outcome Measure Data

Analysis Population Description

The HRQoL Evaluable population included only participants with a baseline QoL assessment and at least 1 follow-up assessment. Time windows were applied post-hoc to increase the size of the analyzable population.

Arm/Group Title	Azacitidine (AZA)	Conventional Care Regimen
Arm/Group Description	Azacitidine 75 mg/m2/day by subcutaneous injection [SC] for 7 days every 28 days, with a 21 day rest period (optimally for at least 6 cycles) plus best supportive care as needed, including antibiotics and blood product transfusions, growth factors, per physician's discretion.	CCRs included: #1 Intensive Chemotherapy: Cytarabine 100-200 mg/m^2 as a continuous intravenous infusion (CIVI) for 7 days and daunorubicin 45 to 60 mg/m^² daily (QD) IV on Days 1, 2 and 3 or Idarubicin 9-12 mg/m^² IV QD for 3 days. Consolidation Therapy (Cycle 2 and 3) = Cytarabine 100-200 mg/m^2 as a CIVI for 3 to 7 days and daunorubicin 45 to 60 mg/m^² QD or Idarubicin 9-12 mg/m^² IV QD on Days 1 and 2. The first consolidation therapy started between Day 28 and Day 70 from start of induction therapy, upon recovery of absolute neutrophil count (ANC) above 1.0 x 10^9/L and platelets above 75 x 10^9/L. The second cycle started between Day 28 and Day 70 from start of first consolidation therapy. Best supportive care (BSC) of antibiotics and transfusions, were given as needed # 2 Low-dose cytarabine 20 mg subcutaneously twice a day (BID) for 10 days every 28 days, plus BSC # 3 BSC only = transfusion of blood products, antibiotics, antifungals and nutritional help
Measure Participants	80	36
Mean (Standard Deviation) [units on a scale]	7.8 (27.28)	10.4 (23.09)

28. Secondary Outcome

Title	HRQoL: Change From Baseline in the EORTC QLQ-C30 Global Health Status-/Quality of Life Domain
Description	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.
Time Frame	Baseline to end of study, at approximately 11-12 months

Outcome Measure Data

Analysis Population Description

The HRQoL Evaluable population included only participants with a baseline QoL assessment and at least 1 follow-up assessment. Time windows were applied post-hoc to increase the size of the analyzable population.

Arm/Group Title	Azacitidine (AZA)	Conventional Care Regimen
Arm/Group Description	Azacitidine 75 mg/m2/day by subcutaneous injection [SC] for 7 days every 28 days, with a 21 day rest period (optimally for at least 6 cycles) plus best supportive care as needed, including antibiotics and blood product transfusions, growth factors, per physician's discretion.	CCRs included: #1 Intensive Chemotherapy: Cytarabine 100-200 mg/m^2 as a continuous intravenous infusion (CIVI) for 7 days and daunorubicin 45 to 60 mg/m^² daily (QD) IV on Days 1, 2 and 3 or Idarubicin 9-12 mg/m^² IV QD for 3 days. Consolidation Therapy (Cycle 2 and 3) = Cytarabine 100-200 mg/m^2 as a CIVI for 3 to 7 days and daunorubicin 45 to 60 mg/m^² QD or Idarubicin 9-12 mg/m^² IV QD on Days 1 and 2. The first consolidation therapy started between Day 28 and Day 70 from start of induction therapy, upon recovery of absolute neutrophil count (ANC) above 1.0 x 10^9/L and platelets above 75 x 10^9/L. The second cycle started between Day 28 and Day 70 from start of first consolidation therapy. Best supportive care (BSC) of antibiotics and transfusions, were given as needed # 2 Low-dose cytarabine 20 mg subcutaneously twice a day (BID) for 10 days every 28 days, plus BSC # 3 BSC only = transfusion of blood products, antibiotics, antifungals and nutritional help
Measure Participants	87	80
Mean (Standard Deviation) [units on a scale]	-4.4 (29.20)	-6.1 (27.90)

29. Secondary Outcome

Title	Healthcare Resource Utilization (HRU): Number of Inpatient Hospitalizations
Description	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.
Time Frame	Day 1 (randomization) to 40 months

Outcome Measure Data

Analysis Population Description

HRU was analyzed for the HRQoL Evaluable Population, a smaller sample than either the ITT population or safety population. Duration of therapy differed between treatment groups. Rate-per-patient year values adjust for these differences.

Arm/Group Title	Azacitidine (AZA)	Conventional Care Regimens (CCR)
Arm/Group Description	Azacitidine 75 mg/m2/day by subcutaneous injection [SC] for 7 days every 28 days, with a 21 day rest period (optimally for at least 6 cycles) plus best supportive care as needed, including antibiotics and blood product transfusions, growth factors, per physician's discretion.	CCRs included: #1 Intensive Chemotherapy: Cytarabine 100-200 mg/m^2 as a continuous intravenous infusion (CIVI) for 7 days and daunorubicin 45 to 60 mg/m^² daily (QD) IV on Days 1, 2 and 3 or Idarubicin 9-12 mg/m^² IV QD for 3 days. Consolidation Therapy (Cycle 2 and 3) = Cytarabine 100-200 mg/m^2 as a CIVI for 3 to 7 days and daunorubicin 45 to 60 mg/m^² QD or Idarubicin 9-12 mg/m^² IV QD on Days 1 and 2. The first consolidation therapy started between Day 28 and Day 70 from start of induction therapy, upon recovery of absolute neutrophil count (ANC) above 1.0 x 10^9/L and platelets above 75 x 10^9/L. The second cycle started between Day 28 and Day 70 from start of first consolidation therapy. Best supportive care (BSC) of antibiotics and transfusions, were given as needed # 2 Low-dose cytarabine 20 mg subcutaneously twice a day (BID) for 10 days every 28 days, plus BSC # 3 BSC only = transfusion of blood products, antibiotics, antifungals and nutritional help
Measure Participants	157	134
Number [participants]	139 57.7%	111 44.9%

30. Secondary Outcome

Title	Healthcare Resource Utilization (HRU): Rate of Inpatient Hospitalizations Per Year
Description	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.
Time Frame	Day 1 (randomization) to 40 months

Outcome Measure Data

Analysis Population Description

HRU was analyzed for the HRQoL Evaluable Population, a smaller sample than either the ITT population or safety population. Duration of therapy differed between treatment groups. Rate-per-patient year values adjust for these differences.

Arm/Group Title	Azacitidine (AZA)	Conventional Care Regimens (CCR)
Arm/Group Description	Azacitidine 75 mg/m2/day by subcutaneous injection [SC] for 7 days every 28 days, with a 21 day rest period (optimally for at least 6 cycles) plus best supportive care as needed, including antibiotics and blood product transfusions, growth factors, per physician's discretion.	CCRs included: #1 Intensive Chemotherapy: Cytarabine 100-200 mg/m^2 as a continuous intravenous infusion (CIVI) for 7 days and daunorubicin 45 to 60 mg/m^² daily (QD) IV on Days 1, 2 and 3 or Idarubicin 9-12 mg/m^² IV QD for 3 days. Consolidation Therapy (Cycle 2 and 3) = Cytarabine 100-200 mg/m^2 as a CIVI for 3 to 7 days and daunorubicin 45 to 60 mg/m^² QD or Idarubicin 9-12 mg/m^² IV QD on Days 1 and 2. The first consolidation therapy started between Day 28 and Day 70 from start of induction therapy, upon recovery of absolute neutrophil count (ANC) above 1.0 x 10^9/L and platelets above 75 x 10^9/L. The second cycle started between Day 28 and Day 70 from start of first consolidation therapy. Best supportive care (BSC) of antibiotics and transfusions, were given as needed # 2 Low-dose cytarabine 20 mg subcutaneously twice a day (BID) for 10 days every 28 days, plus BSC # 3 BSC only = transfusion of blood products, antibiotics, antifungals and nutritional help
Measure Participants	157	134
Number [hospitalizations per patient year]	7.95	4.82

31. Secondary Outcome

Title	HRU: Number of Participants Receiving Transfusions
Description	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.
Time Frame	Day 1 (randomization) to 40 months

Outcome Measure Data

Analysis Population Description

HRU was analyzed for the HRQoL Evaluable Population, a smaller sample than either the ITT population or safety population. Duration of therapy differed between treatment groups. Rate-per-patient year values adjust for these differences.

Arm/Group Title	Azacitidine (AZA)	Conventional Care Regimen
Arm/Group Description	Azacitidine 75 mg/m2/day by subcutaneous injection [SC] for 7 days every 28 days, with a 21 day rest period (optimally for at least 6 cycles) plus best supportive care as needed, including antibiotics and blood product transfusions, growth factors, per physician's discretion.	CCRs included: #1 Intensive Chemotherapy: Cytarabine 100-200 mg/m^2 as a continuous intravenous infusion (CIVI) for 7 days and daunorubicin 45 to 60 mg/m^² daily (QD) IV on Days 1, 2 and 3 or Idarubicin 9-12 mg/m^² IV QD for 3 days. Consolidation Therapy (Cycle 2 and 3) = Cytarabine 100-200 mg/m^2 as a CIVI for 3 to 7 days and daunorubicin 45 to 60 mg/m^² QD or Idarubicin 9-12 mg/m^² IV QD on Days 1 and 2. The first consolidation therapy started between Day 28 and Day 70 from start of induction therapy, upon recovery of absolute neutrophil count (ANC) above 1.0 x 10^9/L and platelets above 75 x 10^9/L. The second cycle started between Day 28 and Day 70 from start of first consolidation therapy. Best supportive care (BSC) of antibiotics and transfusions, were given as needed # 2 Low-dose cytarabine 20 mg subcutaneously twice a day (BID) for 10 days every 28 days, plus BSC # 3 BSC only = transfusion of blood products, antibiotics, antifungals and nutritional help
Measure Participants	157	134
Number [participants]	154 63.9%	134 54.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Azacitidine (AZA), Conventional Care Regimens (CCR)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0721
	Comments
	Method	negative binomial regression analysis
	Comments
Method of Estimation	Estimation Parameter	Relative Ratio
	Estimated Value	0.79
	Confidence Interval	(2-Sided) 95%; 0.62 to 1.02
	Parameter Dispersion	Type: Value:
	Estimation Comments

32. Secondary Outcome

Title	HRU: Rate of Transfusions Per Patient Year
Description	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.
Time Frame	Day 1 (randomization) to 40 months

Outcome Measure Data

Analysis Population Description

HRU was analyzed for the HRQoL Evaluable Population, a smaller sample than either the ITT population or safety population. Duration of therapy differed between treatment groups. Rate-per-patient year values adjust for these differences.

Arm/Group Title	Azacitidine (AZA)	Conventional Care Regimen
Arm/Group Description	Azacitidine 75 mg/m2/day by subcutaneous injection [SC] for 7 days every 28 days, with a 21 day rest period (optimally for at least 6 cycles) plus best supportive care as needed, including antibiotics and blood product transfusions, growth factors, per physician's discretion.	CCRs included: #1 Intensive Chemotherapy: Cytarabine 100-200 mg/m^2 as a continuous intravenous infusion (CIVI) for 7 days and daunorubicin 45 to 60 mg/m^² daily (QD) IV on Days 1, 2 and 3 or Idarubicin 9-12 mg/m^² IV QD for 3 days. Consolidation Therapy (Cycle 2 and 3) = Cytarabine 100-200 mg/m^2 as a CIVI for 3 to 7 days and daunorubicin 45 to 60 mg/m^² QD or Idarubicin 9-12 mg/m^² IV QD on Days 1 and 2. The first consolidation therapy started between Day 28 and Day 70 from start of induction therapy, upon recovery of absolute neutrophil count (ANC) above 1.0 x 10^9/L and platelets above 75 x 10^9/L. The second cycle started between Day 28 and Day 70 from start of first consolidation therapy. Best supportive care (BSC) of antibiotics and transfusions, were given as needed # 2 Low-dose cytarabine 20 mg subcutaneously twice a day (BID) for 10 days every 28 days, plus BSC # 3 BSC only = transfusion of blood products, antibiotics, antifungals and nutritional help
Measure Participants	157	134
Number [transfusions per patient year]	34.23	36.04

33. Secondary Outcome

Title	Number of Participants in the Extension Phase With Treatment Emergent Adverse Events (TEAEs)
Description	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
Time Frame	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

Outcome Measure Data

Analysis Population Description

Safety population includes those enrolled in the extension phase who received at least one dose of study drug.

Arm/Group Title	Azacitidine (AZA)
Arm/Group Description	Azacitidine 75 mg/m2/day by subcutaneous injection [SC] for 7 days every 28 days, with a 21 day rest period (optimally for at least 6 cycles) plus best supportive care as needed, including antibiotics and blood product transfusions, growth factors, per physician's discretion.
Measure Participants	22
At least one Treatment Emergent AE	20 8.3%
At least one TEAE related to study drug	13 5.4%
At least one Grade 3-4 adverse event	13 5.4%
At least 1 Grade 3-4 TEAE related to study drug	7 2.9%
At least 1 Grade 5 TEAE	4 1.7%
At least 1 Grade 5 TEAE related to study drug	0 0%
At least 1 serious TEAE	10 4.1%
At least 1 serious TEAE related to study drug	1 0.4%
At least one serious Grade 3-4 TEAE	8 3.3%
TEAE leading to discontinuation of study drug	3 1.2%
Study drug-related TEAE leading to discontinuation	1 0.4%
TEAE leading to study drug dose reduction	1 0.4%
TEAE leading to study drug dose interruption only	17 7.1%
TEAE causing study dose reduction/interruption	2 0.8%

Adverse Events

Time Frame	From first dose to 1) last dose + 28 days for azacitidine and low-dose cytarabine; 2) last dose + 70 days for intensive chemotherapy; 3) discontinuation for BSC only. Median duration was 191.5, 65.0, 125.0, 124.5 and 360.0 days for each group respectively
Adverse Event Reporting Description	3) discontinuation for BSC only. Median duration was 191.5, 65.0, 125.0, 124.5 and 360.0 days for each group respectively. AEs reported for the Azacitidine group are those that occurred in the treatment phase, AEs reported in the Azacitidine extension group occurred during extension phase
Arm/Group Title	Azacitidine		BSC Only		Low-dose Cytarabine		Intensive Chemotherapy		Azacitidine-extension
Arm/Group Description	Azacitidine 75 mg/m^2/day by subcutaneous injection [SC] for 7 days every 28 days, with a 21 day rest period (optimally for at least 6 cycles) plus best supportive care as needed, including antibiotics and blood product transfusions, growth factors, per physician's discretion		Transfusion of blood products, antibiotics, antifungals and nutritional help		Low-dose cytarabine 20 mg subcutaneously twice a day (BID) for 10 days every 28 days, plus BSC		Cytarabine 100-200 mg/m^2 as a continuous intravenous infusion (CIVI) for 7 days and daunorubicin 45 to 60 mg/m^² daily (QD) IV on Days 1, 2 and 3 or Idarubicin 9-12 mg/m^² IV QD for 3 days. Consolidation Therapy (Cycle 2 and 3) = Cytarabine 100-200 mg/m^2 as a CIVI for 3 to 7 days and daunorubicin 45 to 60 mg/m^² QD or Idarubicin 9-12 mg/m^² IV QD on Days 1 and 2. The first consolidation therapy started between Day 28 and Day 70 from start of induction therapy, upon recovery of absolute neutrophil count (ANC) above 1.0 x 10^9/L and platelets above 75 x 10^9/L. The second cycle started between Day 28 and Day 70 from start of first consolidation therapy. Best supportive care (BSC) of antibiotics and transfusions, were given as needed		Azacitidine 75 mg/m^2/day by subcutaneous injection [SC] for 7 days every 28 days, with a 21 day rest period (optimally for at least 6 cycles) plus best supportive care as needed, including antibiotics and blood product transfusions, growth factors, per physician's discretion.
All Cause Mortality
	Azacitidine		BSC Only		Low-dose Cytarabine		Intensive Chemotherapy		Azacitidine-extension
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Azacitidine		BSC Only		Low-dose Cytarabine		Intensive Chemotherapy		Azacitidine-extension
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	188/236 (79.7%)		30/40 (75%)		118/153 (77.1%)		27/42 (64.3%)		10/22 (45.5%)
Blood and lymphatic system disorders
AGRANULOCYTOSIS	0/236 (0%)		0/40 (0%)		1/153 (0.7%)		0/42 (0%)		0/22 (0%)
ANAEMIA	10/236 (4.2%)		1/40 (2.5%)		11/153 (7.2%)		0/42 (0%)		1/22 (4.5%)
DISSEMINATED INTRAVASCULAR COAGULATION	1/236 (0.4%)		0/40 (0%)		0/153 (0%)		0/42 (0%)		0/22 (0%)
FEBRILE BONE MARROW APLASIA	2/236 (0.8%)		0/40 (0%)		3/153 (2%)		0/42 (0%)		0/22 (0%)
FEBRILE NEUTROPENIA	59/236 (25%)		12/40 (30%)		38/153 (24.8%)		7/42 (16.7%)		4/22 (18.2%)
LEUKOCYTOSIS	4/236 (1.7%)		0/40 (0%)		1/153 (0.7%)		0/42 (0%)		0/22 (0%)
LEUKOPENIA	1/236 (0.4%)		0/40 (0%)		2/153 (1.3%)		0/42 (0%)		0/22 (0%)
LYMPHADENOPATHY	1/236 (0.4%)		0/40 (0%)		0/153 (0%)		0/42 (0%)		0/22 (0%)
NEUTROPENIA	5/236 (2.1%)		1/40 (2.5%)		3/153 (2%)		1/42 (2.4%)		0/22 (0%)
PANCYTOPENIA	0/236 (0%)		0/40 (0%)		1/153 (0.7%)		0/42 (0%)		0/22 (0%)
THROMBOCYTOPENIA	6/236 (2.5%)		0/40 (0%)		14/153 (9.2%)		0/42 (0%)		0/22 (0%)
THROMBOTIC THROMBOCYTOPENIC PURPURA	1/236 (0.4%)		0/40 (0%)		0/153 (0%)		0/42 (0%)		0/22 (0%)
Cardiac disorders
ACUTE CORONARY SYNDROME	2/236 (0.8%)		0/40 (0%)		1/153 (0.7%)		0/42 (0%)		0/22 (0%)
ACUTE LEFT VENTRICULAR FAILURE	1/236 (0.4%)		0/40 (0%)		0/153 (0%)		0/42 (0%)		0/22 (0%)
ACUTE MYOCARDIAL INFARCTION	3/236 (1.3%)		0/40 (0%)		0/153 (0%)		1/42 (2.4%)		0/22 (0%)
ANGINA PECTORIS	0/236 (0%)		0/40 (0%)		1/153 (0.7%)		0/42 (0%)		1/22 (4.5%)
ATRIAL FIBRILLATION	7/236 (3%)		1/40 (2.5%)		3/153 (2%)		2/42 (4.8%)		0/22 (0%)
CARDIAC ARREST	0/236 (0%)		0/40 (0%)		1/153 (0.7%)		0/42 (0%)		0/22 (0%)
CARDIAC FAILURE	2/236 (0.8%)		0/40 (0%)		1/153 (0.7%)		1/42 (2.4%)		0/22 (0%)
CARDIAC FAILURE ACUTE	0/236 (0%)		0/40 (0%)		0/153 (0%)		1/42 (2.4%)		0/22 (0%)
CARDIAC FAILURE CONGESTIVE	0/236 (0%)		1/40 (2.5%)		0/153 (0%)		0/42 (0%)		0/22 (0%)
CARDIO-RESPIRATORY ARREST	1/236 (0.4%)		0/40 (0%)		0/153 (0%)		0/42 (0%)		0/22 (0%)
CARDIOVASCULAR INSUFFICIENCY	1/236 (0.4%)		0/40 (0%)		2/153 (1.3%)		1/42 (2.4%)		0/22 (0%)
ISCHAEMIC CARDIOMYOPATHY	1/236 (0.4%)		0/40 (0%)		0/153 (0%)		0/42 (0%)		0/22 (0%)
LEFT VENTRICULAR FAILURE	1/236 (0.4%)		0/40 (0%)		0/153 (0%)		0/42 (0%)		0/22 (0%)
MYOCARDIAL INFARCTION	0/236 (0%)		0/40 (0%)		1/153 (0.7%)		0/42 (0%)		1/22 (4.5%)
PERICARDIAL EFFUSION	1/236 (0.4%)		0/40 (0%)		0/153 (0%)		1/42 (2.4%)		0/22 (0%)
PERICARDITIS	1/236 (0.4%)		0/40 (0%)		1/153 (0.7%)		0/42 (0%)		0/22 (0%)
SUPRAVENTRICULAR TACHYCARDIA	0/236 (0%)		0/40 (0%)		1/153 (0.7%)		0/42 (0%)		0/22 (0%)
VENTRICULAR TACHYCARDIA	1/236 (0.4%)		0/40 (0%)		0/153 (0%)		0/42 (0%)		0/22 (0%)
Eye disorders
CATARACT	1/236 (0.4%)		0/40 (0%)		0/153 (0%)		0/42 (0%)		0/22 (0%)
CONJUNCTIVAL HAEMORRHAGE	1/236 (0.4%)		0/40 (0%)		0/153 (0%)		0/42 (0%)		0/22 (0%)
Gastrointestinal disorders
ABDOMINAL PAIN	1/236 (0.4%)		0/40 (0%)		1/153 (0.7%)		0/42 (0%)		1/22 (4.5%)
ABDOMINAL PAIN LOWER	0/236 (0%)		0/40 (0%)		2/153 (1.3%)		0/42 (0%)		0/22 (0%)
ANAL HAEMORRHAGE	0/236 (0%)		1/40 (2.5%)		1/153 (0.7%)		0/42 (0%)		0/22 (0%)
ASCITES	0/236 (0%)		0/40 (0%)		0/153 (0%)		1/42 (2.4%)		0/22 (0%)
COLITIS	1/236 (0.4%)		0/40 (0%)		0/153 (0%)		0/42 (0%)		0/22 (0%)
CONSTIPATION	0/236 (0%)		0/40 (0%)		0/153 (0%)		0/42 (0%)		1/22 (4.5%)
DIARRHOEA	4/236 (1.7%)		0/40 (0%)		4/153 (2.6%)		0/42 (0%)		0/22 (0%)
DIVERTICULUM INTESTINAL	1/236 (0.4%)		0/40 (0%)		0/153 (0%)		0/42 (0%)		0/22 (0%)
DUODENAL ULCER HAEMORRHAGE	0/236 (0%)		0/40 (0%)		0/153 (0%)		0/42 (0%)		1/22 (4.5%)
DYSPHAGIA	0/236 (0%)		0/40 (0%)		1/153 (0.7%)		0/42 (0%)		0/22 (0%)
ENTERITIS	0/236 (0%)		1/40 (2.5%)		0/153 (0%)		0/42 (0%)		0/22 (0%)
ENTEROCOLITIS	1/236 (0.4%)		0/40 (0%)		0/153 (0%)		0/42 (0%)		0/22 (0%)
GASTRITIS	1/236 (0.4%)		0/40 (0%)		0/153 (0%)		0/42 (0%)		0/22 (0%)
GASTROINTESTINAL HAEMORRHAGE	1/236 (0.4%)		1/40 (2.5%)		4/153 (2.6%)		0/42 (0%)		0/22 (0%)
HAEMATEMESIS	1/236 (0.4%)		0/40 (0%)		0/153 (0%)		0/42 (0%)		0/22 (0%)
ILEUS	1/236 (0.4%)		0/40 (0%)		0/153 (0%)		0/42 (0%)		0/22 (0%)
INTESTINAL ISCHAEMIA	0/236 (0%)		0/40 (0%)		0/153 (0%)		0/42 (0%)		1/22 (4.5%)
INTESTINAL OBSTRUCTION	1/236 (0.4%)		0/40 (0%)		0/153 (0%)		0/42 (0%)		0/22 (0%)
MELAENA	1/236 (0.4%)		0/40 (0%)		1/153 (0.7%)		0/42 (0%)		0/22 (0%)
MOUTH HAEMORRHAGE	1/236 (0.4%)		1/40 (2.5%)		0/153 (0%)		0/42 (0%)		0/22 (0%)
NAUSEA	2/236 (0.8%)		0/40 (0%)		0/153 (0%)		0/42 (0%)		0/22 (0%)
RECTAL HAEMORRHAGE	1/236 (0.4%)		0/40 (0%)		1/153 (0.7%)		0/42 (0%)		0/22 (0%)
RECTAL ULCER	1/236 (0.4%)		0/40 (0%)		0/153 (0%)		0/42 (0%)		0/22 (0%)
STOMATITIS	1/236 (0.4%)		0/40 (0%)		0/153 (0%)		0/42 (0%)		1/22 (4.5%)
UPPER GASTROINTESTINAL HAEMORRHAGE	1/236 (0.4%)		0/40 (0%)		0/153 (0%)		0/42 (0%)		0/22 (0%)
VOMITING	2/236 (0.8%)		0/40 (0%)		0/153 (0%)		0/42 (0%)		0/22 (0%)
General disorders
ASTHENIA	4/236 (1.7%)		1/40 (2.5%)		3/153 (2%)		0/42 (0%)		0/22 (0%)
CHEST PAIN	0/236 (0%)		0/40 (0%)		2/153 (1.3%)		1/42 (2.4%)		0/22 (0%)
CHILLS	1/236 (0.4%)		0/40 (0%)		1/153 (0.7%)		0/42 (0%)		0/22 (0%)
DEATH	3/236 (1.3%)		0/40 (0%)		2/153 (1.3%)		0/42 (0%)		0/22 (0%)
FATIGUE	3/236 (1.3%)		0/40 (0%)		1/153 (0.7%)		1/42 (2.4%)		0/22 (0%)
GENERAL PHYSICAL HEALTH DETERIORATION	1/236 (0.4%)		0/40 (0%)		1/153 (0.7%)		0/42 (0%)		0/22 (0%)
HYPERTHERMIA	1/236 (0.4%)		0/40 (0%)		0/153 (0%)		0/42 (0%)		0/22 (0%)
INJECTION SITE EXTRAVASATION	1/236 (0.4%)		0/40 (0%)		0/153 (0%)		0/42 (0%)		0/22 (0%)
INJECTION SITE REACTION	2/236 (0.8%)		0/40 (0%)		0/153 (0%)		0/42 (0%)		0/22 (0%)
MALAISE	1/236 (0.4%)		0/40 (0%)		0/153 (0%)		0/42 (0%)		0/22 (0%)
MULTI-ORGAN FAILURE	1/236 (0.4%)		0/40 (0%)		2/153 (1.3%)		0/42 (0%)		0/22 (0%)
OEDEMA PERIPHERAL	0/236 (0%)		1/40 (2.5%)		0/153 (0%)		0/42 (0%)		0/22 (0%)
PAIN	1/236 (0.4%)		0/40 (0%)		1/153 (0.7%)		0/42 (0%)		0/22 (0%)
PYREXIA	25/236 (10.6%)		3/40 (7.5%)		16/153 (10.5%)		2/42 (4.8%)		0/22 (0%)
SUDDEN CARDIAC DEATH	1/236 (0.4%)		0/40 (0%)		1/153 (0.7%)		0/42 (0%)		0/22 (0%)
SUDDEN DEATH	2/236 (0.8%)		0/40 (0%)		0/153 (0%)		0/42 (0%)		0/22 (0%)
Hepatobiliary disorders
CHOLANGITIS	1/236 (0.4%)		0/40 (0%)		0/153 (0%)		0/42 (0%)		0/22 (0%)
CHOLECYSTITIS	1/236 (0.4%)		0/40 (0%)		0/153 (0%)		0/42 (0%)		0/22 (0%)
CHOLECYSTITIS ACUTE	1/236 (0.4%)		0/40 (0%)		1/153 (0.7%)		1/42 (2.4%)		0/22 (0%)
CHOLELITHIASIS	1/236 (0.4%)		0/40 (0%)		0/153 (0%)		0/42 (0%)		0/22 (0%)
HEPATIC FAILURE	0/236 (0%)		0/40 (0%)		2/153 (1.3%)		0/42 (0%)		0/22 (0%)
HYPERBILIRUBINAEMIA	0/236 (0%)		0/40 (0%)		0/153 (0%)		0/42 (0%)		1/22 (4.5%)
Immune system disorders
ANAPHYLACTIC SHOCK	1/236 (0.4%)		0/40 (0%)		0/153 (0%)		0/42 (0%)		0/22 (0%)
Infections and infestations
ABSCESS NECK	1/236 (0.4%)		0/40 (0%)		0/153 (0%)		0/42 (0%)		0/22 (0%)
ABSCESS SOFT TISSUE	1/236 (0.4%)		0/40 (0%)		0/153 (0%)		0/42 (0%)		0/22 (0%)
ACUTE SINUSITIS	1/236 (0.4%)		0/40 (0%)		0/153 (0%)		0/42 (0%)		0/22 (0%)
AEROMONA INFECTION	0/236 (0%)		0/40 (0%)		1/153 (0.7%)		0/42 (0%)		0/22 (0%)
ANAL ABSCESS	1/236 (0.4%)		0/40 (0%)		0/153 (0%)		0/42 (0%)		0/22 (0%)
APPENDICITIS	1/236 (0.4%)		0/40 (0%)		0/153 (0%)		0/42 (0%)		0/22 (0%)
ARTHRITIS INFECTIVE	1/236 (0.4%)		0/40 (0%)		0/153 (0%)		0/42 (0%)		0/22 (0%)
ASPERGILLUS INFECTION	0/236 (0%)		1/40 (2.5%)		0/153 (0%)		0/42 (0%)		0/22 (0%)
BACTERAEMIA	2/236 (0.8%)		0/40 (0%)		1/153 (0.7%)		0/42 (0%)		1/22 (4.5%)
BRONCHITIS	3/236 (1.3%)		0/40 (0%)		1/153 (0.7%)		0/42 (0%)		0/22 (0%)
BRONCHOPNEUMONIA	4/236 (1.7%)		1/40 (2.5%)		1/153 (0.7%)		0/42 (0%)		0/22 (0%)
BRONCHOPULMONARY ASPERGILLOSIS	3/236 (1.3%)		1/40 (2.5%)		0/153 (0%)		0/42 (0%)		1/22 (4.5%)
CANDIDA INFECTION	0/236 (0%)		0/40 (0%)		1/153 (0.7%)		0/42 (0%)		0/22 (0%)
CELLULITIS	5/236 (2.1%)		4/40 (10%)		3/153 (2%)		1/42 (2.4%)		0/22 (0%)
CELLULITIS ORBITAL	1/236 (0.4%)		0/40 (0%)		0/153 (0%)		0/42 (0%)		0/22 (0%)
CLOSTRIDIUM DIFFICILE COLITIS	2/236 (0.8%)		0/40 (0%)		1/153 (0.7%)		0/42 (0%)		0/22 (0%)
CLOSTRIDIUM DIFFICILE INFECTION	1/236 (0.4%)		0/40 (0%)		1/153 (0.7%)		0/42 (0%)		0/22 (0%)
CORYNEBACTERIUM SEPSIS	1/236 (0.4%)		0/40 (0%)		0/153 (0%)		0/42 (0%)		0/22 (0%)
CYSTITIS	0/236 (0%)		0/40 (0%)		1/153 (0.7%)		0/42 (0%)		0/22 (0%)
DEVICE RELATED INFECTION	0/236 (0%)		0/40 (0%)		1/153 (0.7%)		0/42 (0%)		0/22 (0%)
DEVICE RELATED SEPSIS	2/236 (0.8%)		0/40 (0%)		0/153 (0%)		0/42 (0%)		0/22 (0%)
DIVERTICULITIS	4/236 (1.7%)		0/40 (0%)		0/153 (0%)		0/42 (0%)		0/22 (0%)
ENTEROBACTER PNEUMONIA	1/236 (0.4%)		0/40 (0%)		0/153 (0%)		0/42 (0%)		0/22 (0%)
ENTEROCOCCAL BACTERAEMIA	0/236 (0%)		1/40 (2.5%)		1/153 (0.7%)		0/42 (0%)		0/22 (0%)
ENTEROCOCCAL SEPSIS	1/236 (0.4%)		0/40 (0%)		0/153 (0%)		0/42 (0%)		0/22 (0%)
EPIGLOTTITIS	1/236 (0.4%)		0/40 (0%)		0/153 (0%)		0/42 (0%)		0/22 (0%)
ERYSIPELAS	1/236 (0.4%)		0/40 (0%)		0/153 (0%)		0/42 (0%)		0/22 (0%)
ESCHERICHIA BACTERAEMIA	3/236 (1.3%)		0/40 (0%)		1/153 (0.7%)		0/42 (0%)		0/22 (0%)
ESCHERICHIA INFECTION	1/236 (0.4%)		0/40 (0%)		0/153 (0%)		0/42 (0%)		0/22 (0%)
ESCHERICHIA SEPSIS	4/236 (1.7%)		0/40 (0%)		0/153 (0%)		0/42 (0%)		0/22 (0%)
FURUNCLE	1/236 (0.4%)		0/40 (0%)		0/153 (0%)		0/42 (0%)		0/22 (0%)
GASTROENTERITIS	1/236 (0.4%)		0/40 (0%)		1/153 (0.7%)		0/42 (0%)		0/22 (0%)
GASTROENTERITIS CLOSTRIDIAL	1/236 (0.4%)		0/40 (0%)		0/153 (0%)		0/42 (0%)		0/22 (0%)
GASTROINTESTINAL FUNGAL INFECTION	0/236 (0%)		0/40 (0%)		1/153 (0.7%)		0/42 (0%)		0/22 (0%)
GROIN ABSCESS	1/236 (0.4%)		0/40 (0%)		0/153 (0%)		0/42 (0%)		0/22 (0%)
HERPES ZOSTER	1/236 (0.4%)		0/40 (0%)		0/153 (0%)		0/42 (0%)		0/22 (0%)
INFECTED CYST	1/236 (0.4%)		0/40 (0%)		0/153 (0%)		0/42 (0%)		0/22 (0%)
INFECTION	0/236 (0%)		0/40 (0%)		1/153 (0.7%)		0/42 (0%)		1/22 (4.5%)
INFECTIVE EXACERBATION OF CHRONIC OBSTRUCTIVE AIRWAYS DISEASE	0/236 (0%)		0/40 (0%)		1/153 (0.7%)		0/42 (0%)		0/22 (0%)
KLEBSIELLA BACTERAEMIA	0/236 (0%)		0/40 (0%)		1/153 (0.7%)		0/42 (0%)		0/22 (0%)
KLEBSIELLA SEPSIS	1/236 (0.4%)		0/40 (0%)		0/153 (0%)		0/42 (0%)		0/22 (0%)
LIVER ABSCESS	0/236 (0%)		0/40 (0%)		0/153 (0%)		0/42 (0%)		1/22 (4.5%)
LOBAR PNEUMONIA	2/236 (0.8%)		0/40 (0%)		2/153 (1.3%)		0/42 (0%)		0/22 (0%)
LOWER RESPIRATORY TRACT INFECTION	1/236 (0.4%)		1/40 (2.5%)		1/153 (0.7%)		0/42 (0%)		0/22 (0%)
LUNG ABSCESS	1/236 (0.4%)		0/40 (0%)		0/153 (0%)		0/42 (0%)		0/22 (0%)
LUNG INFECTION	2/236 (0.8%)		0/40 (0%)		1/153 (0.7%)		0/42 (0%)		0/22 (0%)
MUMPS	1/236 (0.4%)		0/40 (0%)		0/153 (0%)		0/42 (0%)		0/22 (0%)
NASOPHARYNGITIS	1/236 (0.4%)		0/40 (0%)		0/153 (0%)		0/42 (0%)		0/22 (0%)
NEUTROPENIC SEPSIS	7/236 (3%)		2/40 (5%)		4/153 (2.6%)		1/42 (2.4%)		0/22 (0%)
ORAL CANDIDIASIS	1/236 (0.4%)		0/40 (0%)		0/153 (0%)		0/42 (0%)		0/22 (0%)
OROPHARYNGITIS FUNGAL	0/236 (0%)		0/40 (0%)		0/153 (0%)		1/42 (2.4%)		0/22 (0%)
PARAINFLUENZAE VIRUS INFECTION	1/236 (0.4%)		0/40 (0%)		0/153 (0%)		0/42 (0%)		0/22 (0%)
PERIORBITAL CELLULITIS	0/236 (0%)		1/40 (2.5%)		0/153 (0%)		0/42 (0%)		0/22 (0%)
PERIRECTAL ABSCESS	1/236 (0.4%)		0/40 (0%)		0/153 (0%)		0/42 (0%)		0/22 (0%)
PERITONITIS	0/236 (0%)		0/40 (0%)		1/153 (0.7%)		0/42 (0%)		0/22 (0%)
PHARYNGITIS	2/236 (0.8%)		0/40 (0%)		2/153 (1.3%)		0/42 (0%)		0/22 (0%)
PHARYNGOTONSILLITIS	1/236 (0.4%)		0/40 (0%)		0/153 (0%)		0/42 (0%)		0/22 (0%)
PNEUMONIA	48/236 (20.3%)		3/40 (7.5%)		29/153 (19%)		3/42 (7.1%)		2/22 (9.1%)
PNEUMONIA FUNGAL	3/236 (1.3%)		0/40 (0%)		1/153 (0.7%)		0/42 (0%)		0/22 (0%)
PNEUMONIA KLEBSIELLA	0/236 (0%)		0/40 (0%)		1/153 (0.7%)		0/42 (0%)		0/22 (0%)
PNEUMONIA MYCOPLASMAL	1/236 (0.4%)		0/40 (0%)		0/153 (0%)		0/42 (0%)		0/22 (0%)
PNEUMONIA PARAINFLUENZAE VIRAL	1/236 (0.4%)		0/40 (0%)		0/153 (0%)		0/42 (0%)		0/22 (0%)
PNEUMONIA PSEUDOMONAS AERUGINOSA	1/236 (0.4%)		0/40 (0%)		0/153 (0%)		0/42 (0%)		0/22 (0%)
PNEUMONIA STAPHYLOCOCCAL	0/236 (0%)		0/40 (0%)		1/153 (0.7%)		0/42 (0%)		0/22 (0%)
PNEUMONIA STREPTOCOCCAL	0/236 (0%)		0/40 (0%)		0/153 (0%)		1/42 (2.4%)		0/22 (0%)
PSEUDOMEMBRANOUS COLITIS	3/236 (1.3%)		0/40 (0%)		1/153 (0.7%)		0/42 (0%)		0/22 (0%)
PSEUDOMONAL BACTERAEMIA	0/236 (0%)		0/40 (0%)		1/153 (0.7%)		0/42 (0%)		1/22 (4.5%)
PSEUDOMONAL SEPSIS	3/236 (1.3%)		0/40 (0%)		2/153 (1.3%)		0/42 (0%)		0/22 (0%)
RESPIRATORY TRACT INFECTION	0/236 (0%)		2/40 (5%)		2/153 (1.3%)		0/42 (0%)		0/22 (0%)
SEPSIS	12/236 (5.1%)		1/40 (2.5%)		9/153 (5.9%)		2/42 (4.8%)		0/22 (0%)
SEPTIC SHOCK	4/236 (1.7%)		1/40 (2.5%)		4/153 (2.6%)		4/42 (9.5%)		0/22 (0%)
SINUSITIS	3/236 (1.3%)		0/40 (0%)		0/153 (0%)		0/42 (0%)		1/22 (4.5%)
SINUSITIS FUNGAL	0/236 (0%)		0/40 (0%)		0/153 (0%)		1/42 (2.4%)		0/22 (0%)
SOFT TISSUE INFECTION	1/236 (0.4%)		0/40 (0%)		0/153 (0%)		0/42 (0%)		0/22 (0%)
STAPHYLOCOCCAL BACTERAEMIA	1/236 (0.4%)		0/40 (0%)		0/153 (0%)		1/42 (2.4%)		0/22 (0%)
STAPHYLOCOCCAL SEPSIS	0/236 (0%)		0/40 (0%)		0/153 (0%)		1/42 (2.4%)		0/22 (0%)
SYSTEMIC CANDIDA	0/236 (0%)		0/40 (0%)		0/153 (0%)		0/42 (0%)		1/22 (4.5%)
TONSILLITIS	0/236 (0%)		0/40 (0%)		2/153 (1.3%)		0/42 (0%)		0/22 (0%)
TOOTH INFECTION	2/236 (0.8%)		0/40 (0%)		0/153 (0%)		0/42 (0%)		0/22 (0%)
UPPER RESPIRATORY TRACT INFECTION	2/236 (0.8%)		0/40 (0%)		0/153 (0%)		0/42 (0%)		0/22 (0%)
URINARY TRACT INFECTION	7/236 (3%)		1/40 (2.5%)		3/153 (2%)		0/42 (0%)		0/22 (0%)
UROSEPSIS	2/236 (0.8%)		0/40 (0%)		0/153 (0%)		0/42 (0%)		0/22 (0%)
VAGINITIS GARDNERELLA	0/236 (0%)		0/40 (0%)		1/153 (0.7%)		0/42 (0%)		0/22 (0%)
VULVAL ABSCESS	1/236 (0.4%)		0/40 (0%)		0/153 (0%)		0/42 (0%)		0/22 (0%)
ZYGOMYCOSIS	0/236 (0%)		0/40 (0%)		0/153 (0%)		1/42 (2.4%)		0/22 (0%)
Injury, poisoning and procedural complications
ALLERGIC TRANSFUSION REACTION	0/236 (0%)		0/40 (0%)		1/153 (0.7%)		0/42 (0%)		0/22 (0%)
ANKLE FRACTURE	1/236 (0.4%)		0/40 (0%)		0/153 (0%)		0/42 (0%)		0/22 (0%)
CONCUSSION	1/236 (0.4%)		0/40 (0%)		0/153 (0%)		0/42 (0%)		0/22 (0%)
CRANIOCEREBRAL INJURY	1/236 (0.4%)		0/40 (0%)		0/153 (0%)		0/42 (0%)		0/22 (0%)
FALL	2/236 (0.8%)		0/40 (0%)		0/153 (0%)		0/42 (0%)		0/22 (0%)
FEMUR FRACTURE	1/236 (0.4%)		0/40 (0%)		1/153 (0.7%)		0/42 (0%)		0/22 (0%)
HIP FRACTURE	0/236 (0%)		0/40 (0%)		1/153 (0.7%)		0/42 (0%)		0/22 (0%)
LIGAMENT SPRAIN	1/236 (0.4%)		0/40 (0%)		0/153 (0%)		0/42 (0%)		0/22 (0%)
RIB FRACTURE	1/236 (0.4%)		0/40 (0%)		0/153 (0%)		0/42 (0%)		0/22 (0%)
ROAD TRAFFIC ACCIDENT	1/236 (0.4%)		0/40 (0%)		0/153 (0%)		0/42 (0%)		0/22 (0%)
SUBDURAL HAEMATOMA	1/236 (0.4%)		0/40 (0%)		0/153 (0%)		0/42 (0%)		0/22 (0%)
TENDON RUPTURE	1/236 (0.4%)		0/40 (0%)		0/153 (0%)		0/42 (0%)		0/22 (0%)
TRANSFUSION REACTION	1/236 (0.4%)		0/40 (0%)		0/153 (0%)		0/42 (0%)		0/22 (0%)
Investigations
TROPONIN INCREASED	0/236 (0%)		0/40 (0%)		0/153 (0%)		1/42 (2.4%)		0/22 (0%)
URINE OUTPUT DECREASED	0/236 (0%)		1/40 (2.5%)		0/153 (0%)		0/42 (0%)		0/22 (0%)
WEIGHT DECREASED	0/236 (0%)		0/40 (0%)		1/153 (0.7%)		0/42 (0%)		0/22 (0%)
Metabolism and nutrition disorders
CACHEXIA	1/236 (0.4%)		0/40 (0%)		2/153 (1.3%)		0/42 (0%)		0/22 (0%)
DECREASED APPETITE	0/236 (0%)		0/40 (0%)		0/153 (0%)		0/42 (0%)		1/22 (4.5%)
DEHYDRATION	3/236 (1.3%)		0/40 (0%)		0/153 (0%)		0/42 (0%)		0/22 (0%)
FAILURE TO THRIVE	0/236 (0%)		0/40 (0%)		1/153 (0.7%)		0/42 (0%)		0/22 (0%)
FLUID OVERLOAD	1/236 (0.4%)		0/40 (0%)		0/153 (0%)		0/42 (0%)		0/22 (0%)
HYPERGLYCAEMIA	0/236 (0%)		1/40 (2.5%)		0/153 (0%)		0/42 (0%)		0/22 (0%)
HYPOKALAEMIA	2/236 (0.8%)		0/40 (0%)		0/153 (0%)		0/42 (0%)		0/22 (0%)
HYPONATRAEMIA	2/236 (0.8%)		0/40 (0%)		0/153 (0%)		0/42 (0%)		0/22 (0%)
TUMOUR LYSIS SYNDROME	0/236 (0%)		0/40 (0%)		1/153 (0.7%)		0/42 (0%)		0/22 (0%)
Musculoskeletal and connective tissue disorders
ARTHRALGIA	2/236 (0.8%)		0/40 (0%)		0/153 (0%)		0/42 (0%)		0/22 (0%)
ARTHRITIS	1/236 (0.4%)		0/40 (0%)		0/153 (0%)		0/42 (0%)		0/22 (0%)
BACK PAIN	3/236 (1.3%)		0/40 (0%)		1/153 (0.7%)		0/42 (0%)		0/22 (0%)
BONE PAIN	1/236 (0.4%)		0/40 (0%)		0/153 (0%)		0/42 (0%)		0/22 (0%)
HAEMARTHROSIS	0/236 (0%)		0/40 (0%)		1/153 (0.7%)		0/42 (0%)		0/22 (0%)
MUSCULAR WEAKNESS	2/236 (0.8%)		0/40 (0%)		0/153 (0%)		0/42 (0%)		0/22 (0%)
MYALGIA	1/236 (0.4%)		0/40 (0%)		0/153 (0%)		0/42 (0%)		0/22 (0%)
OSTEOARTHRITIS	0/236 (0%)		0/40 (0%)		0/153 (0%)		0/42 (0%)		1/22 (4.5%)
PAIN IN EXTREMITY	0/236 (0%)		1/40 (2.5%)		0/153 (0%)		0/42 (0%)		0/22 (0%)
SPINAL OSTEOARTHRITIS	0/236 (0%)		0/40 (0%)		1/153 (0.7%)		0/42 (0%)		0/22 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
ACUTE MYELOID LEUKAEMIA	26/236 (11%)		12/40 (30%)		17/153 (11.1%)		0/42 (0%)		1/22 (4.5%)
CHLOROMA	2/236 (0.8%)		0/40 (0%)		0/153 (0%)		0/42 (0%)		0/22 (0%)
LEUKAEMIC INFILTRATION BRAIN	0/236 (0%)		0/40 (0%)		1/153 (0.7%)		0/42 (0%)		0/22 (0%)
OVARIAN CANCER METASTATIC	1/236 (0.4%)		0/40 (0%)		0/153 (0%)		0/42 (0%)		0/22 (0%)
TUMOUR FLARE	1/236 (0.4%)		0/40 (0%)		0/153 (0%)		0/42 (0%)		0/22 (0%)
Nervous system disorders
CEREBRAL HAEMORRHAGE	1/236 (0.4%)		2/40 (5%)		0/153 (0%)		1/42 (2.4%)		0/22 (0%)
CEREBRAL INFARCTION	2/236 (0.8%)		0/40 (0%)		0/153 (0%)		0/42 (0%)		1/22 (4.5%)
CEREBROVASCULAR ACCIDENT	1/236 (0.4%)		0/40 (0%)		2/153 (1.3%)		0/42 (0%)		0/22 (0%)
COGNITIVE DISORDER	1/236 (0.4%)		0/40 (0%)		0/153 (0%)		0/42 (0%)		0/22 (0%)
CONVULSION	1/236 (0.4%)		0/40 (0%)		0/153 (0%)		0/42 (0%)		0/22 (0%)
DIZZINESS	5/236 (2.1%)		0/40 (0%)		0/153 (0%)		0/42 (0%)		1/22 (4.5%)
FEBRILE CONVULSION	0/236 (0%)		1/40 (2.5%)		0/153 (0%)		0/42 (0%)		0/22 (0%)
HAEMORRHAGE INTRACRANIAL	2/236 (0.8%)		0/40 (0%)		0/153 (0%)		1/42 (2.4%)		0/22 (0%)
HEADACHE	1/236 (0.4%)		0/40 (0%)		0/153 (0%)		0/42 (0%)		0/22 (0%)
LOSS OF CONSCIOUSNESS	1/236 (0.4%)		0/40 (0%)		0/153 (0%)		0/42 (0%)		0/22 (0%)
ORTHOSTATIC INTOLERANCE	1/236 (0.4%)		0/40 (0%)		0/153 (0%)		0/42 (0%)		0/22 (0%)
PRESYNCOPE	2/236 (0.8%)		1/40 (2.5%)		0/153 (0%)		0/42 (0%)		0/22 (0%)
SUBARACHNOID HAEMORRHAGE	2/236 (0.8%)		0/40 (0%)		0/153 (0%)		0/42 (0%)		0/22 (0%)
SYNCOPE	4/236 (1.7%)		0/40 (0%)		2/153 (1.3%)		1/42 (2.4%)		1/22 (4.5%)
TRANSIENT ISCHAEMIC ATTACK	0/236 (0%)		0/40 (0%)		1/153 (0.7%)		0/42 (0%)		0/22 (0%)
Psychiatric disorders
CONFUSIONAL STATE	1/236 (0.4%)		0/40 (0%)		0/153 (0%)		0/42 (0%)		0/22 (0%)
Renal and urinary disorders
BLADDER MASS	1/236 (0.4%)		0/40 (0%)		0/153 (0%)		0/42 (0%)		0/22 (0%)
HAEMATURIA	0/236 (0%)		1/40 (2.5%)		0/153 (0%)		0/42 (0%)		1/22 (4.5%)
RENAL COLIC	0/236 (0%)		0/40 (0%)		1/153 (0.7%)		0/42 (0%)		0/22 (0%)
RENAL FAILURE	3/236 (1.3%)		0/40 (0%)		2/153 (1.3%)		0/42 (0%)		0/22 (0%)
RENAL FAILURE ACUTE	3/236 (1.3%)		0/40 (0%)		2/153 (1.3%)		1/42 (2.4%)		0/22 (0%)
RENAL FAILURE CHRONIC	0/236 (0%)		1/40 (2.5%)		0/153 (0%)		0/42 (0%)		0/22 (0%)
RENAL IMPAIRMENT	0/236 (0%)		1/40 (2.5%)		0/153 (0%)		0/42 (0%)		0/22 (0%)
RENAL TUBULAR NECROSIS	1/236 (0.4%)		0/40 (0%)		0/153 (0%)		0/42 (0%)		0/22 (0%)
URINARY RETENTION	0/236 (0%)		0/40 (0%)		1/153 (0.7%)		0/42 (0%)		0/22 (0%)
Respiratory, thoracic and mediastinal disorders
ACUTE PULMONARY OEDEMA	1/236 (0.4%)		0/40 (0%)		1/153 (0.7%)		0/42 (0%)		0/22 (0%)
ACUTE RESPIRATORY DISTRESS SYNDROME	1/236 (0.4%)		0/40 (0%)		0/153 (0%)		1/42 (2.4%)		0/22 (0%)
ACUTE RESPIRATORY FAILURE	2/236 (0.8%)		0/40 (0%)		0/153 (0%)		1/42 (2.4%)		0/22 (0%)
ASTHMA	0/236 (0%)		1/40 (2.5%)		0/153 (0%)		0/42 (0%)		0/22 (0%)
CHRONIC OBSTRUCTIVE PULMONARY DISEASE	0/236 (0%)		0/40 (0%)		1/153 (0.7%)		0/42 (0%)		0/22 (0%)
DYSPNOEA	5/236 (2.1%)		1/40 (2.5%)		3/153 (2%)		1/42 (2.4%)		0/22 (0%)
EPISTAXIS	2/236 (0.8%)		0/40 (0%)		1/153 (0.7%)		0/42 (0%)		0/22 (0%)
LUNG DISORDER	1/236 (0.4%)		0/40 (0%)		2/153 (1.3%)		0/42 (0%)		0/22 (0%)
ORGANISING PNEUMONIA	1/236 (0.4%)		0/40 (0%)		0/153 (0%)		0/42 (0%)		0/22 (0%)
OROPHARYNGEAL PAIN	1/236 (0.4%)		0/40 (0%)		0/153 (0%)		0/42 (0%)		0/22 (0%)
PLEURAL EFFUSION	2/236 (0.8%)		0/40 (0%)		2/153 (1.3%)		1/42 (2.4%)		0/22 (0%)
PNEUMONIA ASPIRATION	0/236 (0%)		1/40 (2.5%)		0/153 (0%)		0/42 (0%)		0/22 (0%)
PNEUMONITIS	1/236 (0.4%)		0/40 (0%)		1/153 (0.7%)		0/42 (0%)		0/22 (0%)
PRODUCTIVE COUGH	1/236 (0.4%)		0/40 (0%)		0/153 (0%)		0/42 (0%)		0/22 (0%)
PULMONARY ALVEOLAR HAEMORRHAGE	1/236 (0.4%)		0/40 (0%)		0/153 (0%)		0/42 (0%)		0/22 (0%)
PULMONARY EMBOLISM	1/236 (0.4%)		0/40 (0%)		1/153 (0.7%)		0/42 (0%)		0/22 (0%)
PULMONARY HAEMORRHAGE	0/236 (0%)		1/40 (2.5%)		1/153 (0.7%)		0/42 (0%)		0/22 (0%)
PULMONARY OEDEMA	2/236 (0.8%)		0/40 (0%)		2/153 (1.3%)		0/42 (0%)		0/22 (0%)
RESPIRATORY FAILURE	3/236 (1.3%)		1/40 (2.5%)		6/153 (3.9%)		2/42 (4.8%)		0/22 (0%)
Skin and subcutaneous tissue disorders
SKIN ULCER	1/236 (0.4%)		0/40 (0%)		0/153 (0%)		0/42 (0%)		0/22 (0%)
Vascular disorders
DEEP VEIN THROMBOSIS	2/236 (0.8%)		1/40 (2.5%)		0/153 (0%)		0/42 (0%)		0/22 (0%)
HAEMATOMA	2/236 (0.8%)		0/40 (0%)		0/153 (0%)		0/42 (0%)		0/22 (0%)
HYPERTENSION	1/236 (0.4%)		0/40 (0%)		0/153 (0%)		0/42 (0%)		0/22 (0%)
HYPOTENSION	4/236 (1.7%)		1/40 (2.5%)		0/153 (0%)		0/42 (0%)		0/22 (0%)
PERIPHERAL ISCHAEMIA	1/236 (0.4%)		0/40 (0%)		0/153 (0%)		0/42 (0%)		0/22 (0%)
PHLEBITIS	1/236 (0.4%)		0/40 (0%)		0/153 (0%)		0/42 (0%)		0/22 (0%)
THROMBOPHLEBITIS SUPERFICIAL	1/236 (0.4%)		0/40 (0%)		0/153 (0%)		0/42 (0%)		0/22 (0%)
Other (Not Including Serious) Adverse Events
	Azacitidine		BSC Only		Low-dose Cytarabine		Intensive Chemotherapy		Azacitidine-extension
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	226/236 (95.8%)		33/40 (82.5%)		151/153 (98.7%)		42/42 (100%)		18/22 (81.8%)
Blood and lymphatic system disorders
ANAEMIA	41/236 (17.4%)		3/40 (7.5%)		32/153 (20.9%)		7/42 (16.7%)		4/22 (18.2%)
FEBRILE NEUTROPENIA	28/236 (11.9%)		2/40 (5%)		21/153 (13.7%)		12/42 (28.6%)		0/22 (0%)
LEUKOCYTOSIS	13/236 (5.5%)		2/40 (5%)		11/153 (7.2%)		0/42 (0%)		0/22 (0%)
LEUKOPENIA	22/236 (9.3%)		0/40 (0%)		15/153 (9.8%)		6/42 (14.3%)		1/22 (4.5%)
NEUTROPENIA	69/236 (29.2%)		1/40 (2.5%)		43/153 (28.1%)		14/42 (33.3%)		6/22 (27.3%)
THROMBOCYTOPENIA	60/236 (25.4%)		2/40 (5%)		37/153 (24.2%)		9/42 (21.4%)		6/22 (27.3%)
Cardiac disorders
ATRIAL FIBRILLATION	12/236 (5.1%)		2/40 (5%)		9/153 (5.9%)		1/42 (2.4%)		1/22 (4.5%)
TACHYCARDIA	5/236 (2.1%)		3/40 (7.5%)		2/153 (1.3%)		2/42 (4.8%)		0/22 (0%)
Gastrointestinal disorders
ABDOMINAL DISTENSION	3/236 (1.3%)		4/40 (10%)		4/153 (2.6%)		0/42 (0%)		0/22 (0%)
ABDOMINAL PAIN	30/236 (12.7%)		3/40 (7.5%)		16/153 (10.5%)		7/42 (16.7%)		1/22 (4.5%)
ABDOMINAL PAIN UPPER	19/236 (8.1%)		0/40 (0%)		6/153 (3.9%)		6/42 (14.3%)		0/22 (0%)
CONSTIPATION	99/236 (41.9%)		9/40 (22.5%)		42/153 (27.5%)		16/42 (38.1%)		1/22 (4.5%)
DIARRHOEA	87/236 (36.9%)		5/40 (12.5%)		34/153 (22.2%)		21/42 (50%)		5/22 (22.7%)
DYSPEPSIA	16/236 (6.8%)		2/40 (5%)		14/153 (9.2%)		6/42 (14.3%)		0/22 (0%)
HAEMORRHOIDS	14/236 (5.9%)		1/40 (2.5%)		7/153 (4.6%)		4/42 (9.5%)		3/22 (13.6%)
MOUTH ULCERATION	11/236 (4.7%)		1/40 (2.5%)		8/153 (5.2%)		1/42 (2.4%)		0/22 (0%)
NAUSEA	93/236 (39.4%)		3/40 (7.5%)		43/153 (28.1%)		24/42 (57.1%)		3/22 (13.6%)
STOMATITIS	20/236 (8.5%)		2/40 (5%)		14/153 (9.2%)		4/42 (9.5%)		2/22 (9.1%)
VOMITING	53/236 (22.5%)		3/40 (7.5%)		24/153 (15.7%)		8/42 (19%)		3/22 (13.6%)
General disorders
ASTHENIA	53/236 (22.5%)		8/40 (20%)		32/153 (20.9%)		5/42 (11.9%)		6/22 (27.3%)
CATHETER SITE PAIN	3/236 (1.3%)		0/40 (0%)		1/153 (0.7%)		3/42 (7.1%)		0/22 (0%)
CHILLS	11/236 (4.7%)		1/40 (2.5%)		7/153 (4.6%)		4/42 (9.5%)		0/22 (0%)
FATIGUE	53/236 (22.5%)		10/40 (25%)		19/153 (12.4%)		4/42 (9.5%)		3/22 (13.6%)
INJECTION SITE ERYTHEMA	29/236 (12.3%)		0/40 (0%)		0/153 (0%)		0/42 (0%)		1/22 (4.5%)
INJECTION SITE PAIN	12/236 (5.1%)		0/40 (0%)		1/153 (0.7%)		0/42 (0%)		1/22 (4.5%)
INJECTION SITE REACTION	30/236 (12.7%)		0/40 (0%)		0/153 (0%)		0/42 (0%)		0/22 (0%)
MALAISE	7/236 (3%)		2/40 (5%)		3/153 (2%)		0/42 (0%)		0/22 (0%)
MUCOSAL INFLAMMATION	8/236 (3.4%)		0/40 (0%)		14/153 (9.2%)		3/42 (7.1%)		0/22 (0%)
OEDEMA	8/236 (3.4%)		0/40 (0%)		3/153 (2%)		1/42 (2.4%)		2/22 (9.1%)
OEDEMA PERIPHERAL	55/236 (23.3%)		6/40 (15%)		33/153 (21.6%)		9/42 (21.4%)		2/22 (9.1%)
PAIN	16/236 (6.8%)		5/40 (12.5%)		5/153 (3.3%)		3/42 (7.1%)		2/22 (9.1%)
PYREXIA	77/236 (32.6%)		7/40 (17.5%)		56/153 (36.6%)		21/42 (50%)		4/22 (18.2%)
Infections and infestations
CELLULITIS	13/236 (5.5%)		3/40 (7.5%)		7/153 (4.6%)		0/42 (0%)		0/22 (0%)
LUNG INFECTION	1/236 (0.4%)		0/40 (0%)		3/153 (2%)		3/42 (7.1%)		0/22 (0%)
NASOPHARYNGITIS	13/236 (5.5%)		2/40 (5%)		5/153 (3.3%)		0/42 (0%)		2/22 (9.1%)
ORAL CANDIDIASIS	16/236 (6.8%)		4/40 (10%)		4/153 (2.6%)		3/42 (7.1%)		0/22 (0%)
ORAL HERPES	15/236 (6.4%)		2/40 (5%)		8/153 (5.2%)		6/42 (14.3%)		0/22 (0%)
PHARYNGITIS	9/236 (3.8%)		1/40 (2.5%)		5/153 (3.3%)		1/42 (2.4%)		2/22 (9.1%)
PNEUMONIA	16/236 (6.8%)		0/40 (0%)		12/153 (7.8%)		4/42 (9.5%)		4/22 (18.2%)
RESPIRATORY TRACT INFECTION	5/236 (2.1%)		2/40 (5%)		4/153 (2.6%)		0/42 (0%)		0/22 (0%)
SKIN INFECTION	5/236 (2.1%)		0/40 (0%)		0/153 (0%)		1/42 (2.4%)		2/22 (9.1%)
UPPER RESPIRATORY TRACT INFECTION	18/236 (7.6%)		1/40 (2.5%)		5/153 (3.3%)		1/42 (2.4%)		1/22 (4.5%)
URINARY TRACT INFECTION	16/236 (6.8%)		3/40 (7.5%)		14/153 (9.2%)		0/42 (0%)		2/22 (9.1%)
Injury, poisoning and procedural complications
CONTUSION	16/236 (6.8%)		3/40 (7.5%)		7/153 (4.6%)		2/42 (4.8%)		2/22 (9.1%)
FALL	14/236 (5.9%)		2/40 (5%)		7/153 (4.6%)		1/42 (2.4%)		1/22 (4.5%)
LACERATION	3/236 (1.3%)		0/40 (0%)		2/153 (1.3%)		0/42 (0%)		2/22 (9.1%)
Investigations
WEIGHT DECREASED	30/236 (12.7%)		3/40 (7.5%)		2/153 (1.3%)		1/42 (2.4%)		1/22 (4.5%)
Metabolism and nutrition disorders
DECREASED APPETITE	61/236 (25.8%)		8/40 (20%)		33/153 (21.6%)		7/42 (16.7%)		2/22 (9.1%)
DEHYDRATION	11/236 (4.7%)		2/40 (5%)		4/153 (2.6%)		1/42 (2.4%)		0/22 (0%)
FLUID OVERLOAD	8/236 (3.4%)		2/40 (5%)		0/153 (0%)		3/42 (7.1%)		0/22 (0%)
FLUID RETENTION	5/236 (2.1%)		0/40 (0%)		0/153 (0%)		3/42 (7.1%)		0/22 (0%)
HYPOALBUMINAEMIA	11/236 (4.7%)		1/40 (2.5%)		11/153 (7.2%)		7/42 (16.7%)		1/22 (4.5%)
HYPOCALCAEMIA	16/236 (6.8%)		0/40 (0%)		6/153 (3.9%)		3/42 (7.1%)		1/22 (4.5%)
HYPOKALAEMIA	54/236 (22.9%)		6/40 (15%)		45/153 (29.4%)		16/42 (38.1%)		3/22 (13.6%)
HYPOMAGNESAEMIA	21/236 (8.9%)		2/40 (5%)		9/153 (5.9%)		6/42 (14.3%)		1/22 (4.5%)
HYPONATRAEMIA	9/236 (3.8%)		0/40 (0%)		12/153 (7.8%)		3/42 (7.1%)		1/22 (4.5%)
HYPOPHOSPHATAEMIA	19/236 (8.1%)		2/40 (5%)		8/153 (5.2%)		6/42 (14.3%)		1/22 (4.5%)
Musculoskeletal and connective tissue disorders
ARTHRALGIA	33/236 (14%)		2/40 (5%)		11/153 (7.2%)		3/42 (7.1%)		2/22 (9.1%)
BACK PAIN	36/236 (15.3%)		5/40 (12.5%)		22/153 (14.4%)		2/42 (4.8%)		1/22 (4.5%)
BONE PAIN	12/236 (5.1%)		2/40 (5%)		4/153 (2.6%)		0/42 (0%)		0/22 (0%)
MUSCULOSKELETAL PAIN	21/236 (8.9%)		2/40 (5%)		3/153 (2%)		1/42 (2.4%)		2/22 (9.1%)
PAIN IN EXTREMITY	26/236 (11%)		2/40 (5%)		11/153 (7.2%)		2/42 (4.8%)		2/22 (9.1%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
ACUTE MYELOID LEUKAEMIA	27/236 (11.4%)		2/40 (5%)		21/153 (13.7%)		1/42 (2.4%)		0/22 (0%)
Nervous system disorders
DIZZINESS	42/236 (17.8%)		3/40 (7.5%)		15/153 (9.8%)		4/42 (9.5%)		1/22 (4.5%)
HEADACHE	31/236 (13.1%)		1/40 (2.5%)		19/153 (12.4%)		6/42 (14.3%)		3/22 (13.6%)
SCIATICA	4/236 (1.7%)		2/40 (5%)		2/153 (1.3%)		0/42 (0%)		0/22 (0%)
Psychiatric disorders
AGITATION	6/236 (2.5%)		3/40 (7.5%)		3/153 (2%)		0/42 (0%)		1/22 (4.5%)
ANXIETY	15/236 (6.4%)		4/40 (10%)		6/153 (3.9%)		2/42 (4.8%)		2/22 (9.1%)
CONFUSIONAL STATE	14/236 (5.9%)		3/40 (7.5%)		8/153 (5.2%)		3/42 (7.1%)		1/22 (4.5%)
INSOMNIA	36/236 (15.3%)		2/40 (5%)		11/153 (7.2%)		4/42 (9.5%)		1/22 (4.5%)
Renal and urinary disorders
HAEMATURIA	5/236 (2.1%)		3/40 (7.5%)		8/153 (5.2%)		1/42 (2.4%)		0/22 (0%)
RENAL FAILURE	7/236 (3%)		2/40 (5%)		3/153 (2%)		3/42 (7.1%)		0/22 (0%)
RENAL FAILURE ACUTE	4/236 (1.7%)		2/40 (5%)		3/153 (2%)		1/42 (2.4%)		0/22 (0%)
URINARY INCONTINENCE	5/236 (2.1%)		2/40 (5%)		1/153 (0.7%)		2/42 (4.8%)		1/22 (4.5%)
Respiratory, thoracic and mediastinal disorders
COUGH	54/236 (22.9%)		6/40 (15%)		36/153 (23.5%)		6/42 (14.3%)		5/22 (22.7%)
DYSPNOEA	41/236 (17.4%)		6/40 (15%)		35/153 (22.9%)		4/42 (9.5%)		1/22 (4.5%)
DYSPNOEA EXERTIONAL	10/236 (4.2%)		2/40 (5%)		6/153 (3.9%)		0/42 (0%)		0/22 (0%)
EPISTAXIS	29/236 (12.3%)		5/40 (12.5%)		21/153 (13.7%)		2/42 (4.8%)		4/22 (18.2%)
HAEMOPTYSIS	9/236 (3.8%)		2/40 (5%)		4/153 (2.6%)		2/42 (4.8%)		0/22 (0%)
HICCUPS	0/236 (0%)		1/40 (2.5%)		0/153 (0%)		3/42 (7.1%)		1/22 (4.5%)
OROPHARYNGEAL PAIN	16/236 (6.8%)		2/40 (5%)		11/153 (7.2%)		4/42 (9.5%)		1/22 (4.5%)
PLEURAL EFFUSION	12/236 (5.1%)		1/40 (2.5%)		2/153 (1.3%)		1/42 (2.4%)		2/22 (9.1%)
PRODUCTIVE COUGH	9/236 (3.8%)		0/40 (0%)		10/153 (6.5%)		3/42 (7.1%)		1/22 (4.5%)
Skin and subcutaneous tissue disorders
ERYTHEMA	18/236 (7.6%)		0/40 (0%)		6/153 (3.9%)		3/42 (7.1%)		0/22 (0%)
PETECHIAE	12/236 (5.1%)		0/40 (0%)		16/153 (10.5%)		1/42 (2.4%)		0/22 (0%)
PRURITUS	25/236 (10.6%)		1/40 (2.5%)		10/153 (6.5%)		6/42 (14.3%)		0/22 (0%)
RASH	26/236 (11%)		0/40 (0%)		14/153 (9.2%)		8/42 (19%)		1/22 (4.5%)
SKIN LESION	4/236 (1.7%)		2/40 (5%)		5/153 (3.3%)		0/42 (0%)		1/22 (4.5%)
SKIN ULCER	7/236 (3%)		2/40 (5%)		2/153 (1.3%)		1/42 (2.4%)		0/22 (0%)
Vascular disorders
HAEMATOMA	16/236 (6.8%)		2/40 (5%)		7/153 (4.6%)		1/42 (2.4%)		2/22 (9.1%)
HYPERTENSION	16/236 (6.8%)		1/40 (2.5%)		13/153 (8.5%)		4/42 (9.5%)		2/22 (9.1%)
HYPOTENSION	19/236 (8.1%)		3/40 (7.5%)		14/153 (9.2%)		1/42 (2.4%)		1/22 (4.5%)
PHLEBITIS	7/236 (3%)		2/40 (5%)		4/153 (2.6%)		2/42 (4.8%)		1/22 (4.5%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The investigator shall have the right to publish and/or present study data provided that the investigator shall (i) furnish the sponsor a copy of any proposed publication or presentation 60 days in advance of the submission and (ii) delete any confidential information of the sponsor and (iii) delay submission for up to 90 days to permit the preparation and filing of intellectual property applications or until sponsor gives its consent in a timely manner.