Acute Myeloid Leukemia
Conditions
Keywords
Acute Myeloid Leukemia, Cytarabine, Vidaza, azacitidine, Intensive Chemotherapy, Low Dose Cytarabine, Celgene
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.
Interventions
DRUGAzacitidine
75 mg/m\^2 subcutaneous (SC) daily for 7 days for 28 day cycles until disease progression or unacceptable toxicity
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
Sponsors
Celgene
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
65 Years to No maximum
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| 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. |
| 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 |
| 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 |
| 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). |
| 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). |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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 |
| 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). |
Countries
Australia, Austria, Belgium, Canada, China, Czechia, France, Germany, Israel, Italy, Netherlands, Poland, Russia, South Korea, Spain, Taiwan, United Kingdom, United States
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.
Participants by arm
| Arm | Count |
|---|---|
| Azacitidine (AZA) 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. | 241 |
| Conventional Care Regimens (CCR) #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. | 247 |
| Total | 488 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Extension Phase | Adverse Event | 5 | 0 |
| Extension Phase | Death | 5 | 0 |
| Extension Phase | Disease Progression | 9 | 0 |
| Extension Phase | Physician Decision | 1 | 0 |
| Extension Phase | Withdrawal by Subject | 2 | 0 |
| Survival Follow-Up Phase | Alive at study closure | 1 | 3 |
| Survival Follow-Up Phase | Death | 116 | 124 |
| Survival Follow-Up Phase | Lost to Follow-up | 2 | 1 |
| Survival Follow-Up Phase | Withdrawal by Subject | 5 | 8 |
| Treatment Phase | Adverse Event | 89 | 66 |
| Treatment Phase | Death | 53 | 58 |
| Treatment Phase | Disease Progression | 16 | 21 |
| Treatment Phase | Lost to Follow-up | 0 | 1 |
| Treatment Phase | Miscellaneous | 32 | 39 |
| Treatment Phase | Protocol Violation | 0 | 1 |
| Treatment Phase | Withdrawal by Subject | 27 | 48 |
Baseline characteristics
| Characteristic | Azacitidine (AZA) | Conventional Care Regimens (CCR) | Total |
|---|---|---|---|
| Age, Continuous | 75.4 years STANDARD_DEVIATION 5.6 | 75.1 years STANDARD_DEVIATION 5.57 | 75.2 years STANDARD_DEVIATION 5.58 |
| Age, Customized <75 years | 103 participants | 120 participants | 223 participants |
| Age, Customized ≥75 years | 138 participants | 127 participants | 265 participants |
| Bone Marrow-Blasts Counts | 66.6 Percentage of Bone Marrow Blasts STANDARD_DEVIATION 24.71 | 70.2 Percentage of Bone Marrow Blasts STANDARD_DEVIATION 22.28 | 68.5 Percentage of Bone Marrow Blasts STANDARD_DEVIATION 23.56 |
| Eastern Cooperative Oncology Group (ECOG) Performance Status 0 = Fully Active | 54 participants | 57 participants | 111 participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status 1 = Restrictive but Ambulatory | 132 participants | 132 participants | 264 participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status 2 = Ambulatory but unable to work | 55 participants | 58 participants | 113 participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status 3 = Limited Self Care | 0 participants | 0 participants | 0 participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status 4 = Completely disabled | 0 participants | 0 participants | 0 participants |
| Sex: Female, Male Female | 102 Participants | 98 Participants | 200 Participants |
| Sex: Female, Male Male | 139 Participants | 149 Participants | 288 Participants |
| World Health Organization Acute Myeloid Leukemia (AML) Classification AML not otherwise specified | 153 participants | 143 participants | 296 participants |
| World Health Organization Acute Myeloid Leukemia (AML) Classification AML with myelodysplasia-related changes | 75 participants | 83 participants | 158 participants |
| World Health Organization Acute Myeloid Leukemia (AML) Classification AML with recurrent genetic abnormalities | 5 participants | 9 participants | 14 participants |
| World Health Organization Acute Myeloid Leukemia (AML) Classification Therapy-related myeloid neoplasms | 8 participants | 12 participants | 158 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 226 / 236 | 33 / 40 | 151 / 153 | 42 / 42 | 18 / 22 |
| serious Total, serious adverse events | 188 / 236 | 30 / 40 | 118 / 153 | 27 / 42 | 10 / 22 |
Outcome results
Primary
Kaplan-Meier Estimates for Overall Survival
Overall Survival was defined as the time from randomization to death from any cause. Overall survival was calculated by the formula: date of death - date of randomization + 1. Participants surviving at the end of the follow-up period or who withdrew consent to follow-up were censored at the date of last contact. Participants who were lost to follow-up were censored at the date last known alive.
Time frame: Day 1 (randomization) to 40 months
Population: 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 | Measure | Value (MEDIAN) |
|---|---|---|
| Azacitidine (AZA) | Kaplan-Meier Estimates for Overall Survival | 10.4 months |
| Conventional Care Regimens (CCR) | Kaplan-Meier Estimates for Overall Survival | 6.5 months |
p-value: 0.082995% CI: [0.69, 1.02]Log Rank
p-value: 0.100995% CI: [0.69, 1.03]Log Rank
Secondary
Duration of Remission Assessed by the IRC Based on Kaplan-Meier Estimates
The time from the date CR or CRi was first documented until the date of documented relapse from CR/CRi. Duration of remission was defined only for those participants who achieved a CR or CRi, as determined by the IRC. Participants who were lost to follow-up without documented relapse, or were alive at last follow-up without documented relapse were censored at the date of their last response assessment.
Time frame: Day 1 (randomization) to 40 months; date of the first documented CR or CRi until date of first documented relapse.
Population: Includes those who achieved a CR or CRi and assessed by the IRC; numbers of ITT participants in each treatment group
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Azacitidine (AZA) | Duration of Remission Assessed by the IRC Based on Kaplan-Meier Estimates | 10.4 months |
| Conventional Care Regimens (CCR) | Duration of Remission Assessed by the IRC Based on Kaplan-Meier Estimates | 12.3 months |
Secondary
Event-free Survival (EFS)
Event-free survival was defined as the interval from the date of randomization to the date of treatment failure, progressive disease, relapse after complete remission (CR) or complete remission with incomplete blood count recovery (CRi), death from any cause, or lost to follow-up, whichever occurs first. Participants who were still alive without any of these events were censored at the date of their last response assessment.
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
Population: 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 | Measure | Value (MEDIAN) |
|---|---|---|
| Azacitidine (AZA) | Event-free Survival (EFS) | 6.7 months |
| Conventional Care Regimens (CCR) | Event-free Survival (EFS) | 4.8 months |
Comparison: Median is estimated from a Kaplan-Meier distribution of EFSp-value: 0.149595% CI: [0.72, 1.05]Log Rank
Secondary
Healthcare Resource Utilization (HRU): Number of Inpatient Hospitalizations
HRU was defined as any consumption of healthcare resources directly or indirectly related to the treatment of the patient. HRU Analysis may help in evaluating potential costs and budget impact of new treatments from a payer perspective.
Time frame: Day 1 (randomization) to 40 months
Population: 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 | Measure | Value (NUMBER) |
|---|---|---|
| Azacitidine (AZA) | Healthcare Resource Utilization (HRU): Number of Inpatient Hospitalizations | 139 participants |
| Conventional Care Regimens (CCR) | Healthcare Resource Utilization (HRU): Number of Inpatient Hospitalizations | 111 participants |
Secondary
Healthcare Resource Utilization (HRU): Rate of Inpatient Hospitalizations Per Year
HRU was defined as any consumption of healthcare resources directly or indirectly related to the treatment of the patient. HRU Analysis may help in evaluating potential costs and budget impact of new treatments from a payer perspective. The rate of inpatient hospitalizations per patient year was calculated as the total number of hospitalizations divided by the total number of patient-years followed in the study period. Patient-years (PY) were calculated as the duration from baseline to last available HRQL assessment for each patient.
Time frame: Day 1 (randomization) to 40 months
Population: 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 | Measure | Value (NUMBER) |
|---|---|---|
| Azacitidine (AZA) | Healthcare Resource Utilization (HRU): Rate of Inpatient Hospitalizations Per Year | 7.95 hospitalizations per patient year |
| Conventional Care Regimens (CCR) | Healthcare Resource Utilization (HRU): Rate of Inpatient Hospitalizations Per Year | 4.82 hospitalizations per patient year |
Secondary
Health Related Quality of Life (HRQoL): Change From Baseline in the European Organization for Research and Treatment of Cancer Cancer Quality of Life Questionnaire for Patients With Cancer (EORTC QLQ-C30) Fatigue Domain
The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Fatigue Scale is scored between 0 and 100, with a high score indicating a higher level of symptoms. Negative change from Baseline values indicate reduction in fatigue (i.e. improvement in symptom) and positive values indicate increases in fatigue (i.e. worsening of symptom).
Time frame: Baseline to Cycle 3; at approximately 3 months
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Azacitidine (AZA) | 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 | -1.5 units on a scale | Standard Deviation 24.69 |
| Conventional Care Regimens (CCR) | 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 | -1.9 units on a scale | Standard Deviation 27.54 |
Secondary
Health Related Quality of Life (HRQoL): Change From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Cancer (EORTC QLQ-C30) Fatigue Domain
The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Fatigue Scale is scored between 0 and 100, with a high score indicating a higher level of symptoms. Negative change from Baseline values indicate reduction in fatigue (i.e. improvement in symptom) and positive values indicate increases in fatigue (i.e. worsening of symptom).
Time frame: Baseline to Cycle 5, at approximately 5 months
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Azacitidine (AZA) | 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 | -2.8 units on a scale | Standard Deviation 27.36 |
| Conventional Care Regimens (CCR) | 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 | -7.1 units on a scale | Standard Deviation 27.61 |
Secondary
Health Related Quality of Life (HRQoL): Change From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Cancer (EORTC QLQ-C30) Fatigue Domain
The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Fatigue Scale is scored between 0 and 100, with a high score indicating a higher level of symptoms. Negative change from Baseline values indicate reduction in fatigue (i.e. improvement in symptom) and positive values indicate increases in fatigue (i.e. worsening of symptom).
Time frame: Baseline to End of Study; at approximately 11-12 months
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Azacitidine (AZA) | 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 | 8.9 units on a scale | Standard Deviation 33.54 |
| Conventional Care Regimens (CCR) | 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 | 6.1 units on a scale | Standard Deviation 34.19 |
Secondary
Health Related Quality of Life (HRQoL): Change From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Cancer (EORTC QLQ-C30) Fatigue Domain
The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Fatigue Scale is scored between 0 and 100, with a high score indicating a higher level of symptoms. Negative change from Baseline values indicate reduction in fatigue (i.e. improvement in symptom) and positive values indicate increases in fatigue (i.e. worsening of symptom).
Time frame: Baseline to Cycle 9, at approximately 9 months
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Azacitidine (AZA) | 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 | -9.0 units on a scale | Standard Deviation 27.9 |
| Conventional Care Regimens (CCR) | 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 | -10.2 units on a scale | Standard Deviation 33.85 |
Secondary
Health Related Quality of Life (HRQoL): Change From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Cancer (EORTC QLQ-C30) Fatigue Domain
The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Fatigue Scale is scored between 0 and 100, with a high score indicating a higher level of symptoms. Negative change from Baseline values indicate reduction in fatigue (i.e. improvement in symptom) and positive values indicate increases in fatigue (i.e. worsening of symptom).
Time frame: Baseline to Cycle 7, at approximately 7 months
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Azacitidine (AZA) | 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 | -6.1 units on a scale | Standard Deviation 26.9 |
| Conventional Care Regimens (CCR) | 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 | -12.2 units on a scale | Standard Deviation 30.45 |
Secondary
HRQoL: Change From Baseline in the EORTC QLQ-C30 Dyspnea
The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Dyspnea scale is scored between 0 and 100, with a high score indicating a higher level of symptoms. Negative change from Baseline values indicate decreased dyspnea (i.e. improvement in symptom) and positive values indicate increased dyspnea (i.e. worsening of symptom).
Time frame: Baseline to Cycle 9, at approximately 9 months
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Azacitidine (AZA) | HRQoL: Change From Baseline in the EORTC QLQ-C30 Dyspnea | -4.9 units on a scale | Standard Deviation 26.93 |
| Conventional Care Regimens (CCR) | HRQoL: Change From Baseline in the EORTC QLQ-C30 Dyspnea | -2.8 units on a scale | Standard Deviation 26.87 |
Secondary
HRQoL: Change From Baseline in the EORTC QLQ-C30 Dyspnea
The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Dyspnea scale is scored between 0 and 100, with a high score indicating a higher level of symptoms. Negative change from Baseline values indicate decreased dyspnea (i.e. improvement in symptom) and positive values indicate increased dyspnea (i.e. worsening of symptom).
Time frame: Baseline to Cycle 3, at approximately 3 months
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Azacitidine (AZA) | HRQoL: Change From Baseline in the EORTC QLQ-C30 Dyspnea | 5.1 units on a scale | Standard Deviation 26.88 |
| Conventional Care Regimens (CCR) | HRQoL: Change From Baseline in the EORTC QLQ-C30 Dyspnea | -1.7 units on a scale | Standard Deviation 30.69 |
Secondary
HRQoL: Change From Baseline in the EORTC QLQ-C30 Dyspnea
The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Dyspnea scale is scored between 0 and 100, with a high score indicating a higher level of symptoms. Negative change from Baseline values indicate decreased dyspnea (i.e. improvement in symptom) and positive values indicate increased dyspnea (i.e. worsening of symptom).
Time frame: Baseline to Cycle 5, at approximately 5 months
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Azacitidine (AZA) | HRQoL: Change From Baseline in the EORTC QLQ-C30 Dyspnea | 3.9 units on a scale | Standard Deviation 27.49 |
| Conventional Care Regimens (CCR) | HRQoL: Change From Baseline in the EORTC QLQ-C30 Dyspnea | -6.6 units on a scale | Standard Deviation 28.18 |
Secondary
HRQoL: Change From Baseline in the EORTC QLQ-C30 Dyspnea
The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Dyspnea scale is scored between 0 and 100, with a high score indicating a higher level of symptoms. Negative change from Baseline values indicate decreased dyspnea (i.e. improvement in symptom) and positive values indicate increased dyspnea (i.e. worsening of symptom).
Time frame: Baseline to Cycle 7, at approximately 7 months
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Azacitidine (AZA) | HRQoL: Change From Baseline in the EORTC QLQ-C30 Dyspnea | 0.4 units on a scale | Standard Deviation 29.93 |
| Conventional Care Regimens (CCR) | HRQoL: Change From Baseline in the EORTC QLQ-C30 Dyspnea | -8.8 units on a scale | Standard Deviation 28.61 |
Secondary
HRQoL: Change From Baseline in the EORTC QLQ-C30 Dyspnea
The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Dyspnea scale is scored between 0 and 100, with a high score indicating a higher level of symptoms. Negative change from Baseline values indicate decreased dyspnea (i.e. improvement in symptom) and positive values indicate increased dyspnea (i.e. worsening of symptom).
Time frame: Baseline to end of study, at approximately 11-12 months
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Azacitidine (AZA) | HRQoL: Change From Baseline in the EORTC QLQ-C30 Dyspnea | 12.6 units on a scale | Standard Deviation 31.43 |
| Conventional Care Regimens (CCR) | HRQoL: Change From Baseline in the EORTC QLQ-C30 Dyspnea | 6.3 units on a scale | Standard Deviation 35.22 |
Secondary
HRQoL: Change From Baseline in the EORTC QLQ-C30 Global Health Status-/Quality of Life Domain
The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Global Health Status/QOL scale is scored between 0 and 100, with a high score indicating better Global Health Status/QOL. Negative change from Baseline values indicate deterioration in Global Health Status/QOL and positive values indicate improvement.
Time frame: Baseline to Cycle 7, at approximately 7 months
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Azacitidine (AZA) | HRQoL: Change From Baseline in the EORTC QLQ-C30 Global Health Status-/Quality of Life Domain | 5.1 units on a scale | Standard Deviation 25.84 |
| Conventional Care Regimens (CCR) | HRQoL: Change From Baseline in the EORTC QLQ-C30 Global Health Status-/Quality of Life Domain | 8.7 units on a scale | Standard Deviation 27.91 |
Secondary
HRQoL: Change From Baseline in the EORTC QLQ-C30 Global Health Status-/Quality of Life Domain
The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Global Health Status/QOL scale is scored between 0 and 100, with a high score indicating better Global Health Status/QOL. Negative change from Baseline values indicate deterioration in Global Health Status/QOL and positive values indicate improvement.
Time frame: Baseline to end of study, at approximately 11-12 months
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Azacitidine (AZA) | HRQoL: Change From Baseline in the EORTC QLQ-C30 Global Health Status-/Quality of Life Domain | -4.4 units on a scale | Standard Deviation 29.2 |
| Conventional Care Regimens (CCR) | HRQoL: Change From Baseline in the EORTC QLQ-C30 Global Health Status-/Quality of Life Domain | -6.1 units on a scale | Standard Deviation 27.9 |
Secondary
HRQoL: Change From Baseline in the EORTC QLQ-C30 Global Health Status-/Quality of Life Domain
The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Global Health Status/QOL scale is scored between 0 and 100, with a high score indicating better Global Health Status/QOL. Negative change from Baseline values indicate deterioration in Global Health Status/QOL and positive values indicate improvement.
Time frame: Baseline to Cycle 9, at approximately 9 months
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Azacitidine (AZA) | HRQoL: Change From Baseline in the EORTC QLQ-C30 Global Health Status-/Quality of Life Domain | 7.8 units on a scale | Standard Deviation 27.28 |
| Conventional Care Regimens (CCR) | HRQoL: Change From Baseline in the EORTC QLQ-C30 Global Health Status-/Quality of Life Domain | 10.4 units on a scale | Standard Deviation 23.09 |
Secondary
HRQoL: Change From Baseline in the EORTC QLQ-C30 Global Health Status-/Quality of Life Domain
The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Global Health Status/QOL scale is scored between 0 and 100, with a high score indicating better Global Health Status/QOL. Negative change from Baseline values indicate deterioration in Global Health Status/QOL and positive values indicate improvement.
Time frame: Baseline to Cycle 3, at approximately 3 months
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Azacitidine (AZA) | HRQoL: Change From Baseline in the EORTC QLQ-C30 Global Health Status-/Quality of Life Domain | 0.9 units on a scale | Standard Deviation 20.97 |
| Conventional Care Regimens (CCR) | HRQoL: Change From Baseline in the EORTC QLQ-C30 Global Health Status-/Quality of Life Domain | 3.8 units on a scale | Standard Deviation 26.42 |
Secondary
HRQoL: Change From Baseline in the EORTC QLQ-C30 Global Health Status-/Quality of Life Domain
The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Global Health Status/QOL scale is scored between 0 and 100, with a high score indicating better Global Health Status/QOL. Negative change from Baseline values indicate deterioration in Global Health Status/QOL and positive values indicate improvement.
Time frame: Baseline to Cycle 5, at approximately 5 months
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Azacitidine (AZA) | HRQoL: Change From Baseline in the EORTC QLQ-C30 Global Health Status-/Quality of Life Domain | 1.6 units on a scale | Standard Deviation 22.5 |
| Conventional Care Regimens (CCR) | HRQoL: Change From Baseline in the EORTC QLQ-C30 Global Health Status-/Quality of Life Domain | 9.0 units on a scale | Standard Deviation 24.82 |
Secondary
HRQoL: Change From Baseline in the EORTC QLQ-C30 Physical Functioning Domain
The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 PhysicalFunctioning Scale is scored between 0 and 100, with a high score indicating better functioning. Negative change from Baseline values indicate deterioration in functioning and positive values indicate improvement.
Time frame: Baseline to Cycle 7, at approximately 7 months
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Azacitidine (AZA) | HRQoL: Change From Baseline in the EORTC QLQ-C30 Physical Functioning Domain | 1.6 units on a scale | Standard Deviation 18.75 |
| Conventional Care Regimens (CCR) | HRQoL: Change From Baseline in the EORTC QLQ-C30 Physical Functioning Domain | 1.5 units on a scale | Standard Deviation 23.08 |
Secondary
HRQoL: Change From Baseline in the EORTC QLQ-C30 Physical Functioning Domain
The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 PhysicalFunctioning Scale is scored between 0 and 100, with a high score indicating better functioning. Negative change from Baseline values indicate deterioration in functioning and positive values indicate improvement.
Time frame: Baseline to Cycle 9, at approximately 9 months
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Azacitidine (AZA) | HRQoL: Change From Baseline in the EORTC QLQ-C30 Physical Functioning Domain | 3.5 units on a scale | Standard Deviation 18.26 |
| Conventional Care Regimens (CCR) | HRQoL: Change From Baseline in the EORTC QLQ-C30 Physical Functioning Domain | -0.4 units on a scale | Standard Deviation 22.81 |
Secondary
HRQoL: Change From Baseline in the EORTC QLQ-C30 Physical Functioning Domain
The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 PhysicalFunctioning Scale is scored between 0 and 100, with a high score indicating better functioning. Negative change from Baseline values indicate deterioration in functioning and positive values indicate improvement.
Time frame: Baseline to end of study, at approximately 11-12 months
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Azacitidine (AZA) | HRQoL: Change From Baseline in the EORTC QLQ-C30 Physical Functioning Domain | -13.0 units on a scale | Standard Deviation 26.74 |
| Conventional Care Regimens (CCR) | HRQoL: Change From Baseline in the EORTC QLQ-C30 Physical Functioning Domain | -9.4 units on a scale | Standard Deviation 26.43 |
Secondary
HRQoL: Change From Baseline in the EORTC QLQ-C30 Physical Functioning Domain
The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 PhysicalFunctioning Scale is scored between 0 and 100, with a high score indicating better functioning. Negative change from Baseline values indicate deterioration in functioning and positive values indicate improvement.
Time frame: Baseline to Cycle 3, at approximately 3 months
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Azacitidine (AZA) | HRQoL: Change From Baseline in the EORTC QLQ-C30 Physical Functioning Domain | -4.2 units on a scale | Standard Deviation 17.98 |
| Conventional Care Regimens (CCR) | HRQoL: Change From Baseline in the EORTC QLQ-C30 Physical Functioning Domain | -0.3 units on a scale | Standard Deviation 18.85 |
Secondary
HRQoL: Change From Baseline in the EORTC QLQ-C30 Physical Functioning Domain
The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 PhysicalFunctioning Scale is scored between 0 and 100, with a high score indicating better functioning. Negative change from Baseline values indicate deterioration in functioning and positive values indicate improvement.
Time frame: Baseline to Cycle 5, at approximately 5 months
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Azacitidine (AZA) | HRQoL: Change From Baseline in the EORTC QLQ-C30 Physical Functioning Domain | -4.4 units on a scale | Standard Deviation 19.25 |
| Conventional Care Regimens (CCR) | HRQoL: Change From Baseline in the EORTC QLQ-C30 Physical Functioning Domain | -1.3 units on a scale | Standard Deviation 20.41 |
Secondary
HRU: Number of Participants Receiving Transfusions
Count of study participants who had transfusions during the treatment phase. HRU is defined as any consumption of healthcare resources directly or indirectly related to the treatment of the patient. HRU Analysis may help in evaluating potential costs and budget impact of new treatments from a payer perspective.
Time frame: Day 1 (randomization) to 40 months
Population: 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 | Measure | Value (NUMBER) |
|---|---|---|
| Azacitidine (AZA) | HRU: Number of Participants Receiving Transfusions | 154 participants |
| Conventional Care Regimens (CCR) | HRU: Number of Participants Receiving Transfusions | 134 participants |
p-value: 0.072195% CI: [0.62, 1.02]negative binomial regression analysis
Secondary
HRU: Rate of Transfusions Per Patient Year
HRU is defined as any consumption of healthcare resources directly or indirectly related to the treatment of the patient. HRU Analysis may help in evaluating potential costs and budget impact of new treatments from a payer perspective. The rate of transfusions per patient year was calculated as the total number of transfusions divided by the total number of patient-years followed in the study period. Patient-years (PY) were calculated as the duration from baseline to last available HRQL assessment for each patient.
Time frame: Day 1 (randomization) to 40 months
Population: 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 | Measure | Value (NUMBER) |
|---|---|---|
| Azacitidine (AZA) | HRU: Rate of Transfusions Per Patient Year | 34.23 transfusions per patient year |
| Conventional Care Regimens (CCR) | HRU: Rate of Transfusions Per Patient Year | 36.04 transfusions per patient year |
Secondary
Number of Participants in the Extension Phase With Treatment Emergent Adverse Events (TEAEs)
AEs = any noxious, unintended, or untoward medical occurrence that may appear or worsen during the course of a study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the participant's health, regardless of cause. Serious AE (SAE) = any AE which results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; constitutes an important medical event. The severity of AEs were graded based upon the participants symptoms according to the Common Terminology Criteria for Adverse Events (CTCAE, Version 4.0); AEs were evaluated for severity according to the following scale: Grade 1 = Mild - transient or mild discomfort; no medical intervention required; Grade 2 = Moderate - mild to moderate limitation in activity; Grade 3 = Severe; Grade 4 = Life threatening; Grade 5 = Death
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
Population: Safety population includes those enrolled in the extension phase who received at least one dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Azacitidine (AZA) | Number of Participants in the Extension Phase With Treatment Emergent Adverse Events (TEAEs) | At least one Treatment Emergent AE | 20 participants |
| Azacitidine (AZA) | Number of Participants in the Extension Phase With Treatment Emergent Adverse Events (TEAEs) | At least one TEAE related to study drug | 13 participants |
| Azacitidine (AZA) | Number of Participants in the Extension Phase With Treatment Emergent Adverse Events (TEAEs) | At least one Grade 3-4 adverse event | 13 participants |
| Azacitidine (AZA) | Number of Participants in the Extension Phase With Treatment Emergent Adverse Events (TEAEs) | At least 1 Grade 3-4 TEAE related to study drug | 7 participants |
| Azacitidine (AZA) | Number of Participants in the Extension Phase With Treatment Emergent Adverse Events (TEAEs) | At least 1 Grade 5 TEAE | 4 participants |
| Azacitidine (AZA) | Number of Participants in the Extension Phase With Treatment Emergent Adverse Events (TEAEs) | At least 1 Grade 5 TEAE related to study drug | 0 participants |
| Azacitidine (AZA) | Number of Participants in the Extension Phase With Treatment Emergent Adverse Events (TEAEs) | At least 1 serious TEAE | 10 participants |
| Azacitidine (AZA) | Number of Participants in the Extension Phase With Treatment Emergent Adverse Events (TEAEs) | At least 1 serious TEAE related to study drug | 1 participants |
| Azacitidine (AZA) | Number of Participants in the Extension Phase With Treatment Emergent Adverse Events (TEAEs) | At least one serious Grade 3-4 TEAE | 8 participants |
| Azacitidine (AZA) | Number of Participants in the Extension Phase With Treatment Emergent Adverse Events (TEAEs) | TEAE leading to discontinuation of study drug | 3 participants |
| Azacitidine (AZA) | Number of Participants in the Extension Phase With Treatment Emergent Adverse Events (TEAEs) | Study drug-related TEAE leading to discontinuation | 1 participants |
| Azacitidine (AZA) | Number of Participants in the Extension Phase With Treatment Emergent Adverse Events (TEAEs) | TEAE leading to study drug dose reduction | 1 participants |
| Azacitidine (AZA) | Number of Participants in the Extension Phase With Treatment Emergent Adverse Events (TEAEs) | TEAE leading to study drug dose interruption only | 17 participants |
| Azacitidine (AZA) | Number of Participants in the Extension Phase With Treatment Emergent Adverse Events (TEAEs) | TEAE causing study dose reduction/interruption | 2 participants |
Secondary
Number of Participants Who Achieved a Cytogenetic Complete Response (CRc-10) as Determined by the IRC.
The CRc is a normal karyotype defined as no clonal abnormalities after review of at least 10 metaphases using conventional cytogenetic techniques. Cytogenetic complete remission rate (CRc) is when the following criteria are met: 1) CR criteria met and 2) an abnormal karyotype is present at baseline and 3) there is reversion to normal karyotype at the time of CR (based on ≥ 10 metaphases), where date of cytogenetic sample = date of BM sample used for the CR assessment
Time frame: Day 1 (randomization) to 40 months
Population: 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 | Measure | Value (NUMBER) |
|---|---|---|
| Azacitidine (AZA) | Number of Participants Who Achieved a Cytogenetic Complete Response (CRc-10) as Determined by the IRC. | 5 participants |
| Conventional Care Regimens (CCR) | Number of Participants Who Achieved a Cytogenetic Complete Response (CRc-10) as Determined by the IRC. | 15 participants |
p-value: 0.0376Fisher Exact
Secondary
Number of Participants With Adverse Events (AEs)
AEs = any noxious, unintended, or untoward medical occurrence that may appear or worsen during the course of a study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the participant's health, regardless of cause. Serious AE (SAE) = any AE which results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; constitutes an important medical event. The severity of AEs were graded based upon the participants symptoms according to the Common Terminology Criteria for Adverse Events (CTCAE, Version 4.0); AEs were evaluated for severity according to the following scale: Grade 1 = Mild - transient or mild discomfort; no medical intervention required; Grade 2 = Moderate - mild to moderate limitation in activity; Grade 3 = Severe; Grade 4 = Life threatening; Grade 5 = Death
Time frame: Day 1 (randomization) up to last visit completed; final data cut off of 28 Feb 2017
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Azacitidine (AZA) | Number of Participants With Adverse Events (AEs) | At least one Treatment Emergent AE | 234 participants |
| Azacitidine (AZA) | Number of Participants With Adverse Events (AEs) | At least one TEAE related to study drug | 188 participants |
| Azacitidine (AZA) | Number of Participants With Adverse Events (AEs) | Grade 3-4 adverse event | 207 participants |
| Azacitidine (AZA) | Number of Participants With Adverse Events (AEs) | Grade 3-4 adverse event related to any study drug | 125 participants |
| Azacitidine (AZA) | Number of Participants With Adverse Events (AEs) | At least one Grade 5 (leading to death) TEAE | 56 participants |
| Azacitidine (AZA) | Number of Participants With Adverse Events (AEs) | Grade 5 adverse event related to any study drug | 12 participants |
| Azacitidine (AZA) | Number of Participants With Adverse Events (AEs) | Serious TEAE | 188 participants |
| Azacitidine (AZA) | Number of Participants With Adverse Events (AEs) | Serious TEAE related to any study drug | 87 participants |
| Azacitidine (AZA) | Number of Participants With Adverse Events (AEs) | TEAE leading to discontinuation of study drug | 110 participants |
| Azacitidine (AZA) | Number of Participants With Adverse Events (AEs) | Study drug-related TEAE leading to discontinuation | 22 participants |
| Azacitidine (AZA) | Number of Participants With Adverse Events (AEs) | TEAE leading to study drug dose reduction | 8 participants |
| Azacitidine (AZA) | Number of Participants With Adverse Events (AEs) | TEAE leading to study drug dose interruption | 116 participants |
| Azacitidine (AZA) | Number of Participants With Adverse Events (AEs) | TEAE causing study drug dose reduction/disruption | 13 participants |
| Conventional Care Regimens (CCR) | Number of Participants With Adverse Events (AEs) | Grade 3-4 adverse event related to any study drug | 0 participants |
| Conventional Care Regimens (CCR) | Number of Participants With Adverse Events (AEs) | TEAE causing study drug dose reduction/disruption | 0 participants |
| Conventional Care Regimens (CCR) | Number of Participants With Adverse Events (AEs) | TEAE leading to study drug dose reduction | 0 participants |
| Conventional Care Regimens (CCR) | Number of Participants With Adverse Events (AEs) | Serious TEAE related to any study drug | 0 participants |
| Conventional Care Regimens (CCR) | Number of Participants With Adverse Events (AEs) | Grade 3-4 adverse event | 26 participants |
| Conventional Care Regimens (CCR) | Number of Participants With Adverse Events (AEs) | At least one Treatment Emergent AE | 36 participants |
| Conventional Care Regimens (CCR) | Number of Participants With Adverse Events (AEs) | Study drug-related TEAE leading to discontinuation | 0 participants |
| Conventional Care Regimens (CCR) | Number of Participants With Adverse Events (AEs) | TEAE leading to discontinuation of study drug | 0 participants |
| Conventional Care Regimens (CCR) | Number of Participants With Adverse Events (AEs) | Grade 5 adverse event related to any study drug | 0 participants |
| Conventional Care Regimens (CCR) | Number of Participants With Adverse Events (AEs) | At least one Grade 5 (leading to death) TEAE | 23 participants |
| Conventional Care Regimens (CCR) | Number of Participants With Adverse Events (AEs) | At least one TEAE related to study drug | 0 participants |
| Conventional Care Regimens (CCR) | Number of Participants With Adverse Events (AEs) | TEAE leading to study drug dose interruption | 0 participants |
| Conventional Care Regimens (CCR) | Number of Participants With Adverse Events (AEs) | Serious TEAE | 30 participants |
| Conventional Care Regimen #2 Low-dose Cytarabine | Number of Participants With Adverse Events (AEs) | TEAE leading to study drug dose reduction | 2 participants |
| Conventional Care Regimen #2 Low-dose Cytarabine | Number of Participants With Adverse Events (AEs) | Grade 3-4 adverse event related to any study drug | 90 participants |
| Conventional Care Regimen #2 Low-dose Cytarabine | Number of Participants With Adverse Events (AEs) | At least one Grade 5 (leading to death) TEAE | 38 participants |
| Conventional Care Regimen #2 Low-dose Cytarabine | Number of Participants With Adverse Events (AEs) | TEAE causing study drug dose reduction/disruption | 7 participants |
| Conventional Care Regimen #2 Low-dose Cytarabine | Number of Participants With Adverse Events (AEs) | Grade 5 adverse event related to any study drug | 10 participants |
| Conventional Care Regimen #2 Low-dose Cytarabine | Number of Participants With Adverse Events (AEs) | Serious TEAE | 118 participants |
| Conventional Care Regimen #2 Low-dose Cytarabine | Number of Participants With Adverse Events (AEs) | TEAE leading to study drug dose interruption | 61 participants |
| Conventional Care Regimen #2 Low-dose Cytarabine | Number of Participants With Adverse Events (AEs) | Serious TEAE related to any study drug | 56 participants |
| Conventional Care Regimen #2 Low-dose Cytarabine | Number of Participants With Adverse Events (AEs) | TEAE leading to discontinuation of study drug | 68 participants |
| Conventional Care Regimen #2 Low-dose Cytarabine | Number of Participants With Adverse Events (AEs) | Study drug-related TEAE leading to discontinuation | 20 participants |
| Conventional Care Regimen #2 Low-dose Cytarabine | Number of Participants With Adverse Events (AEs) | At least one Treatment Emergent AE | 153 participants |
| Conventional Care Regimen #2 Low-dose Cytarabine | Number of Participants With Adverse Events (AEs) | At least one TEAE related to study drug | 124 participants |
| Conventional Care Regimen #2 Low-dose Cytarabine | Number of Participants With Adverse Events (AEs) | Grade 3-4 adverse event | 141 participants |
| Conventional Care Regimen #1 Intensive Chemotherapy | Number of Participants With Adverse Events (AEs) | Study drug-related TEAE leading to discontinuation | 5 participants |
| Conventional Care Regimen #1 Intensive Chemotherapy | Number of Participants With Adverse Events (AEs) | Serious TEAE related to any study drug | 14 participants |
| Conventional Care Regimen #1 Intensive Chemotherapy | Number of Participants With Adverse Events (AEs) | Grade 3-4 adverse event related to any study drug | 29 participants |
| Conventional Care Regimen #1 Intensive Chemotherapy | Number of Participants With Adverse Events (AEs) | At least one Treatment Emergent AE | 42 participants |
| Conventional Care Regimen #1 Intensive Chemotherapy | Number of Participants With Adverse Events (AEs) | Serious TEAE | 27 participants |
| Conventional Care Regimen #1 Intensive Chemotherapy | Number of Participants With Adverse Events (AEs) | Grade 5 adverse event related to any study drug | 4 participants |
| Conventional Care Regimen #1 Intensive Chemotherapy | Number of Participants With Adverse Events (AEs) | Grade 3-4 adverse event | 37 participants |
| Conventional Care Regimen #1 Intensive Chemotherapy | Number of Participants With Adverse Events (AEs) | At least one TEAE related to study drug | 39 participants |
| Conventional Care Regimen #1 Intensive Chemotherapy | Number of Participants With Adverse Events (AEs) | At least one Grade 5 (leading to death) TEAE | 9 participants |
| Conventional Care Regimen #1 Intensive Chemotherapy | Number of Participants With Adverse Events (AEs) | TEAE leading to discontinuation of study drug | 11 participants |
| Conventional Care Regimen #1 Intensive Chemotherapy | Number of Participants With Adverse Events (AEs) | TEAE causing study drug dose reduction/disruption | 0 participants |
| Conventional Care Regimen #1 Intensive Chemotherapy | Number of Participants With Adverse Events (AEs) | TEAE leading to study drug dose interruption | 4 participants |
| Conventional Care Regimen #1 Intensive Chemotherapy | Number of Participants With Adverse Events (AEs) | TEAE leading to study drug dose reduction | 2 participants |
Secondary
One-year Overall Survival Rate
Kaplan Meier methods were used to estimate the 1-year survival probabilities for time to death from any cause. Estimates of the 1-year (365 day) survival probabilities and corresponding 95% confidence intervals (CI) were presented by treatment group. The CI for the difference in the 1-year survival probabilities was derived using Greenwoods variance estimate.
Time frame: From Day 1 (randomization) to 40 months
Population: 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 | Measure | Value (NUMBER) |
|---|---|---|
| Azacitidine (AZA) | One-year Overall Survival Rate | 46.5 percentage of participants |
| Conventional Care Regimens (CCR) | One-year Overall Survival Rate | 34.3 percentage of participants |
95% CI: [3.5, 21]
Secondary
Percentage of Participants Who Achieved a Morphologic CR + CRi as Determined by the Independent Review Committee (IRC) Based on International Working Group (IWG) Response Criteria for Acute Myeloid Leukemia (AML)
A complete remission (CR) is defined as a leukemia-free state defined as less than 5% blasts in a BM aspirate with marrow spicules and with at least 200 nucleated cells (there should be no blasts with Auer rods), an absolute neutrophil count (ANC) of ≥ 1 x 10\^9/L, a platelet count ≥ 100 x 10\^9/L, and transfusion independence (no transfusions for 1 week prior to each assessment). No duration of these findings is required for confirmation of this response. A CR with incomplete blood count recovery (CRi) is defined as \<5% BM blasts with the ANC count \< 1 x 10\^9/L and/or the platelet count may be \< 100 x 10\^9/L. Where the date of the hematology assessment used is the earliest on or following the date of the BM sample up to 8 days after the BM date.
Time frame: Day 1 (randomization) to 40 months
Population: 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 | Measure | Value (NUMBER) |
|---|---|---|
| Azacitidine (AZA) | 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) | 27.8 percentage of participants |
| Conventional Care Regimens (CCR) | 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) | 25.1 percentage of participants |
p-value: 0.5384Fisher Exact
Secondary
Relapse-Free Survival (RFS) for Participants Who Achieved a Complete Remission (CR) or Complete Remission With Incomplete Blood Count Recovery (CRi)
Relapse-free survival was defined as the interval from the date of first documented CR or CRi to the date of relapse, death from any cause, or lost to follow-up, whichever occurred first. Participants who were still alive and in continuous CR or CRi were censored at the date of their last response assessment.
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
Population: Participants who achieved a CR or CRi
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Azacitidine (AZA) | Relapse-Free Survival (RFS) for Participants Who Achieved a Complete Remission (CR) or Complete Remission With Incomplete Blood Count Recovery (CRi) | 9.3 months |
| Conventional Care Regimens (CCR) | Relapse-Free Survival (RFS) for Participants Who Achieved a Complete Remission (CR) or Complete Remission With Incomplete Blood Count Recovery (CRi) | 10.5 months |
Comparison: Median is estimated from a Kaplan-Meier distribution of RFSp-value: 0.583295% CI: [0.75, 1.66]Log Rank