Myelodysplastic Syndromes
Conditions
Brief summary
The purpose of this study is to determine whether patients with high-risk myelodysplastic syndromes (MDS) treated with azacitidine have improved survival compared to conventional care treatments. The study will also assess the effect of treatments on response, duration of response, and transformation to acute myeloid leukemia (AML). The study will continue for 12 months following last patient enrolled. See study AZA PH GL 2003 CL 001 E for information about the extension to this study.
Detailed description
Comparison/Control Interventions offered the physician three options: * Best supportive care (BSC) alone, * Low-dose cytarabine subcutaneously for 14 days every 28 to 42 days, or * Standard chemotherapy administered for induction as a continuous intravenous infusion of cytarabine over 7 days plus an anthracycline (daunorubicin, idarubicin, or mitoxantrone) on Days 1, 2, and 3; and, for those eligible, 1 or 2 consolidation cycles administered as continuous intravenous infusions of cytarabine for 3 to 7 days with the same anthracycline that was used at induction on Days 1 and 2 (each cycle between 28 to 70 days from the start of the previous cycle). All three options included best supportive care. Neither the experimental group (azacitidine) nor any of the comparison/control options allowed use of erythropoietin. Duration of Intervention: Patients will be treated until death, withdrawal, unacceptable toxicity or conclusion of the study.
Interventions
DRUGAzacitidine
Azacitidine was injected subcutaneously (SC) at an initial dose of 75mg/m\^2/day for 7 days. The 7-day dosing was repeated every 28 days with dose adjustment based on predefined hematology and renal laboratory results. Number of cycles: Azacitidine treatment was to be continued until the end of the study unless treatment was discontinued due to unacceptable toxicity, relapse after complete or partial response, transformation to AML or disease progression.
OTHERPhysician Choice
Physician Choice was one of three options: * Best supportive care (BSC) alone, * Low-dose cytarabine subcutaneously for 14 days every 28 to 42 days, or * Standard chemotherapy administered for induction as a continuous intravenous infusion of cytarabine over 7 days plus an anthracycline (daunorubicin, idarubicin, or mitoxantrone) on Days 1, 2, and 3; and, for those eligible, 1 or 2 consolidation cycles administered as continuous intravenous infusions of cytarabine for 3 to 7 days with the same anthracycline that was used at induction on Days 1 and 2 (each cycle between 28 to 70 days from the start of the previous cycle). All three options included best supportive care
Sponsors
Celgene
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Have a diagnosis of refractory anemia with excess blasts or refractory anemia with excess blasts in transformation according to the French-American-British classification system for myelodysplastic syndromes (MDS) and a relatively high risk of acute myeloid leukemia (AML) transformation, with an International Prognostic Scoring System score of INT-2 or High. * Be 18 years of age or older * Have a life expectancy of at least 3 months * Be unlikely to proceed to bone marrow or stem cell transplantation therapy following remission * Have serum bilirubin levels less than or equal to 1.5 times the upper limit of normal range for the laboratory * Have serum glutamic-oxaloacetic transaminase (aspartate aminotransferase) or serum glutamic-pyruvic transaminase (alanine aminotransferase) levels less than or equal to 2 times the upper limit of normal (unless these are considered to be related to transfusion-induced secondary hemosiderosis) * Have serum creatinine levels less than or equal to 1.5 times the upper limit of normal
Exclusion criteria
* Secondary myelodysplastic syndromes (MDS) * Prior treatment with azacitidine; * Prior history of acute myeloid leukemia (AML); * Malignant disease diagnosed within prior 12 months; * Metastatic disease; * Hepatic tumors; * Radiation, chemotherapy, cytotoxic therapy for non-MDS conditions within prior 12 months; * Prior transplantation or cytotoxic therapy to treat MDS; * Serious medical illness likely to limit survival to 12 months or less; * Treatment with erythropoietin or myeloid growth factors during prior 21 days or androgenic hormones during prior 13 days; * Active HIV, viral hepatitis type B or C; * Treatment with investigational drugs during prior 30 days; * Within the 28-day screening period, documented red cell folate deficiency, as evidenced by red blood cell folate (not serum folate) or vitamin B12 deficiency
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Kaplan-Meier Estimates for Median Time to Death From Any Cause | Day 1 (randomization) to 42 months | Kaplan-Meier estimates for the median months until death from any cause within the intent-to-treat population. Patients surviving at the end of the follow-up period were censored at the date of last contact. If a patient withdrew consent to follow-up or was lost to follow-up, the patient was censored as of the last date of contact. |
| Summary of Subgroup Analyses for Kaplan-Meier Estimates for Time to Death From Any Cause | Day 1 (randomization) to 42 months | Kaplan-Meier estimates for the median months until death from any cause within the intent-to-treat population. Patients surviving at the end of the follow-up period were censored at the date of last contact. If a patient withdrew consent to follow-up or was lost to follow-up, the patient was censored as of the last date of contact. Subgroups that were analyzed are age, gender, French-American-British (FAB) classification, World Health Organization (WHO) classification and International Prognostic Scoring System (IPSS) classification. |
| Number of Participants Who Died | 42 months | Count of participants who died during the study |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Summary of Participants' Red Blood Cell (RBC) Transfusion Status for Participants Who Were Transfusion Independent at Baseline | Day 1 (randomization) to 42 months | Summary of dependence and independence from red blood cell (RBC) transfusion at baseline and during treatment, for patients who were independent at baseline. A patient was considered transfusion independent at baseline if the patient had no transfusions during the 56 days prior to randomization. During study, a patient was considered transfusion independent during the on-treatment period if the patient had no transfusions during any 56 consecutive days or more. Otherwise, the patient was considered transfusion dependent. |
| Summary of Participants' Platelet Transfusion Status for Participants Who Were Transfusion Dependent at Baseline | Day 1 (randomization) to 42 months | Summary of dependence and independence from platelet transfusion at baseline and during treatment for patients who were dependent at baseline. A patient was considered transfusion independent at baseline if the patient had no transfusions during the 56 days prior to randomization. During study, a patient was considered transfusion independent during the on-treatment period if the patient had no transfusions during any 56 consecutive days or more. Otherwise, the patient was considered transfusion dependent. |
| Summary of Participants' Platelet Transfusion Status for Participants Who Were Transfusion Independent at Baseline | Day 1 (randomization) to 42 months | Summary of dependence and independence from platelet transfusion at baseline and during treatment for patients who were independent at baseline. A patient was considered transfusion independent at baseline if the patient had no transfusions during the 56 days prior to randomization. During study, a patient was considered transfusion independent during the on-treatment period if the patient had no transfusions during any 56 consecutive days or more. Otherwise, the patient was considered transfusion dependent. |
| Number of Participants Considered Hematologic Responders by Investigator Determinations Using International Working Group (IWG 2000) Criteria for Myelodysplastic Syndrome (MDS) | Day 1 to 42 months | Investigator determined responses followed IWG criteria for * complete remission(CR): repeat bone marrow show \<5% myeloblasts, and peripheral blood evaluations lasting \>=2 months of hemoglobin(\>110 g/L), neutrophils(\>=1.5x10\^9/L), platelets(\>=100x10\^9/L), blasts (0%) and no dysplasia * partial remission(PR) is the same as CR for peripheral blood: bone marrow shows blasts decrease by \>=50% or a less advanced FAB classification from pretreatment * stable disease(SD) is a failure to achieve at least a partial remission, but with no evidence of progression for at least 2 months. |
| Kaplan-Meier Estimate for Median Time to Transformation to Acute Myeloid Leukemia (AML) or Death From Any Cause, Whichever Occurred First | Day 1 (randomization) to 42 months | The time to transformation to AML or death from any cause (whichever occurred first) was defined as the number of days from the date of randomization until the date of documented AML transformation or death from any cause. Patients who did not transform to AML or die were censored at the date of last follow-up. |
| Time to Disease Progression, Relapse After Complete or Partial Remission, or Death From Any Cause | Day 1 (randomization) to 42 months | The time to disease progression, relapse after complete or partial remission (CR, PR), or death from any cause was defined as the time from the date of randomization until the first date of documented disease progression, relapse after CR or PR, or death from any cause. |
| Duration of Any Hematologic Improvement | Day 1 (randomization) to 42 months | The duration of improvement was defined as the time from the date of hematologic improvement until the date of first documented progression or relapse after hematologic improvement or death from any cause. |
| Number of Infections Per Treatment Year Requiring Intravenous Antibiotics, Antifungals or Antivirals | Day 1 (randomization) to 42 months | The on-treatment adverse event rate of infection requiring IV antibiotics, antifungals, or antivirals per patient-years. The on-treatment period was considered the period from the date of randomization to the last treatment study visit. |
| Number of Participants in Different Categories of Adverse Experiences During Core Study Period | Day 1 (randomization) to 42 months | Patient counts for a variety of subsets of adverse experiences for the core study period (day 1 to 42 months). The individual options for Conventional Care Regimens (Best Supportive Care Only, Low-Dose Cytarabine, and Standard Chemotherapy) are presented as separate treatments. |
| Number of Participants Showing Hematologic Improvement Using International Working Group (IWG 2000) Criteria for Myelodysplastic Syndrome (MDS) Assessed by Independent Review Committee | Day 1 to 42 months | IWG 2000 Criteria: Pretreatment=hemoglobin \<100g/L or RBC transfusion-dependent, platelet count \<100x10\^9/L or platelet transfusion dependent, absolute neutrophil count \<1.5x10\^9/L. Erythroid response: Major-\>20g/L increase or transfusion independent. Minor- 10-20g/L increase or \>=50% decrease in transfusion requirements. Platelet response: Major-absolute increase of \>=30x10\^9/L or platelet transfusion independence. Minor-\>=50% increase. Neutrophil response: Major-\>=100% increase or an absolute increase of \>0.5x10\^9/L. Minor-\>=100% increase and absolute increase of \<0.5x10\^9/L. |
| Kaplan-Meier Estimates for Median Time to Transformation to Acute Myeloid Leukemia (AML) | Day 1 (randomization) to 42 months | The time to transformation to AML was defined as the number of days from the date of randomization until the date of documented AML transformation, defined as a bone marrow blast count ≥ 30% independent of baseline bone marrow count. Patients who did not transform to AML were censored at the date of last follow-up or date of death. |
| Summary of Participants' Red Blood Cell (RBC) Transfusion Status for Participants Who Were Transfusion Dependent at Baseline | Day 1 (randomization) to 42 months | Summary of dependence and independence from red blood cell (RBC) transfusion at baseline and during treatment, for patients who were dependent at baseline. A patient was considered transfusion independent at baseline if the patient had no transfusions during the 56 days prior to randomization. During study, a patient was considered transfusion independent during the on-treatment period if the patient had no transfusions during any 56 consecutive days or more. Otherwise, the patient was considered transfusion dependent. |
Countries
Australia, Bulgaria, Czechia, France, Germany, Greece, Hungary, Italy, Netherlands, Poland, Russia, Spain, Sweden, United Kingdom, United States
Participant flow
Pre-assignment details
738 patients screened from 98 investigator sites. Randomized patients contributed by 79 investigator sites.
Participants by arm
| Arm | Count |
|---|---|
| Azacitidine Azacitidine, 75 mg/m\^2/day given by subcutaneous injection for 7 days of every 28 day cycle, plus best supportive care. | 179 |
| Conventional Care Physician choice of low dose cytarabine, standard chemotherapy, or best supportive care (consisting of blood products, growth factors, antibiotics) | 179 |
| Total | 358 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 19 | 10 |
| Overall Study | Different Central+Local Pathology Review | 0 | 1 |
| Overall Study | Disease Progression | 23 | 20 |
| Overall Study | Lack of Efficacy | 11 | 18 |
| Overall Study | Lost to Follow-up | 1 | 1 |
| Overall Study | Not Documented | 0 | 2 |
| Overall Study | Physician Decision | 0 | 2 |
| Overall Study | Protocol Violation | 1 | 7 |
| Overall Study | Withdrawal by Subject | 15 | 37 |
Baseline characteristics
| Characteristic | Conventional Care | Total | Azacitidine |
|---|---|---|---|
| Age, Continuous | 69.2 years STANDARD_DEVIATION 7.87 | 68.6 years STANDARD_DEVIATION 7.73 | 68.0 years STANDARD_DEVIATION 7.57 |
| Body Surface Area | 1.8 meters squared STANDARD_DEVIATION 0.19 | 1.9 meters squared STANDARD_DEVIATION 0.19 | 1.9 meters squared STANDARD_DEVIATION 0.19 |
| French-American-British (FAB) Classification Acute myeloid leukemia | 1 participants | 2 participants | 1 participants |
| French-American-British (FAB) Classification Indeterminate | 6 participants | 9 participants | 3 participants |
| French-American-British (FAB) Classification Modified chronic myelomonocytic leukemia | 5 participants | 11 participants | 6 participants |
| French-American-British (FAB) Classification Myeloproliferative disease | 2 participants | 6 participants | 4 participants |
| French-American-British (FAB) Classification RAEB in transformation | 62 participants | 123 participants | 61 participants |
| French-American-British (FAB) Classification Refractory anemia with excess blasts (RAEB) | 103 participants | 207 participants | 104 participants |
| International Prognostic Scoring System (IPSS) High risk (2.5-3.5) | 85 participants | 167 participants | 82 participants |
| International Prognostic Scoring System (IPSS) Indeterminate | 8 participants | 19 participants | 11 participants |
| International Prognostic Scoring System (IPSS) Intermediate risk level 1 (0.5-1.0) | 13 participants | 18 participants | 5 participants |
| International Prognostic Scoring System (IPSS) Intermediate risk level 2 (1.5-2.0) | 70 participants | 146 participants | 76 participants |
| International Prognostic Scoring System (IPSS) Not applicable | 3 participants | 8 participants | 5 participants |
| Race/Ethnicity, Customized Asian/Oriental | 3 participants | 5 participants | 2 participants |
| Race/Ethnicity, Customized Black or African American | 0 participants | 0 participants | 0 participants |
| Race/Ethnicity, Customized Caucasian | 175 participants | 352 participants | 177 participants |
| Race/Ethnicity, Customized Hispanic | 1 participants | 1 participants | 0 participants |
| Race/Ethnicity, Customized Other | 0 participants | 0 participants | 0 participants |
| Sex: Female, Male Female | 60 Participants | 107 Participants | 47 Participants |
| Sex: Female, Male Male | 119 Participants | 251 Participants | 132 Participants |
| Weight | 74.6 kilograms STANDARD_DEVIATION 13.58 | 75.6 kilograms STANDARD_DEVIATION 13.85 | 76.5 kilograms STANDARD_DEVIATION 14.08 |
| World Health Organization (WHO) Classification Acute myeloid leukemia | 58 participants | 113 participants | 55 participants |
| World Health Organization (WHO) Classification Chronic myelomonocytic leukemia - 1 (CMMoL-1) | 0 participants | 1 participants | 1 participants |
| World Health Organization (WHO) Classification Chronic myelomonocytic leukemia - 2 (CMMoL-2) | 5 participants | 15 participants | 10 participants |
| World Health Organization (WHO) Classification Indeterminate | 4 participants | 5 participants | 1 participants |
| World Health Organization (WHO) Classification Refractory anemia with excess blasts - 1 | 17 participants | 31 participants | 14 participants |
| World Health Organization (WHO) Classification Refractory anemia with excess blasts - 2 | 95 participants | 193 participants | 98 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 175 / 175 | 86 / 102 | 44 / 44 | 19 / 19 |
| serious Total, serious adverse events | 114 / 175 | 71 / 102 | 27 / 44 | 14 / 19 |
Outcome results
Primary
Kaplan-Meier Estimates for Median Time to Death From Any Cause
Kaplan-Meier estimates for the median months until death from any cause within the intent-to-treat population. Patients surviving at the end of the follow-up period were censored at the date of last contact. If a patient withdrew consent to follow-up or was lost to follow-up, the patient was censored as of the last date of contact.
Time frame: Day 1 (randomization) to 42 months
Population: Intent to treat population. Includes participants who died and participants who were censored.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Azacitidine | Kaplan-Meier Estimates for Median Time to Death From Any Cause | 24.46 months |
| Conventional Care | Kaplan-Meier Estimates for Median Time to Death From Any Cause | 15.02 months |
Comparison: A 95% CI range value of 'does not exist' is not accommodated in the results table, so all the 95% CI range values are offered here.~Azacitidine: low range of 17.9 months and high range of 'does not exist'.~Conventional Care: low range of 9.8 and high range of 17.0 months.p-value: 0.0001Log Rank
p-value: 0.000295% CI: [0.43, 0.77]Regression, Cox
Primary
Number of Participants Who Died
Count of participants who died during the study
Time frame: 42 months
Population: Intent to treat population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Azacitidine | Number of Participants Who Died | 82 participants |
| Conventional Care | Number of Participants Who Died | 113 participants |
Primary
Summary of Subgroup Analyses for Kaplan-Meier Estimates for Time to Death From Any Cause
Kaplan-Meier estimates for the median months until death from any cause within the intent-to-treat population. Patients surviving at the end of the follow-up period were censored at the date of last contact. If a patient withdrew consent to follow-up or was lost to follow-up, the patient was censored as of the last date of contact. Subgroups that were analyzed are age, gender, French-American-British (FAB) classification, World Health Organization (WHO) classification and International Prognostic Scoring System (IPSS) classification.
Time frame: Day 1 (randomization) to 42 months
Population: Intent to treat population. Includes participants who died and those who were censored.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Azacitidine | Summary of Subgroup Analyses for Kaplan-Meier Estimates for Time to Death From Any Cause | FAB: Refractory anemia with excess blasts (RAEB) | 34.66 months |
| Azacitidine | Summary of Subgroup Analyses for Kaplan-Meier Estimates for Time to Death From Any Cause | FAB: RAEB in transformation | 17.25 months |
| Azacitidine | Summary of Subgroup Analyses for Kaplan-Meier Estimates for Time to Death From Any Cause | Age >= 75 years | 8.92 months |
| Azacitidine | Summary of Subgroup Analyses for Kaplan-Meier Estimates for Time to Death From Any Cause | WHO: RAEB 1 | 11.54 months |
| Azacitidine | Summary of Subgroup Analyses for Kaplan-Meier Estimates for Time to Death From Any Cause | Gender: Male | 24.46 months |
| Azacitidine | Summary of Subgroup Analyses for Kaplan-Meier Estimates for Time to Death From Any Cause | WHO: RAEB 2 | 21.11 months |
| Azacitidine | Summary of Subgroup Analyses for Kaplan-Meier Estimates for Time to Death From Any Cause | Age >= 65 years | 24.46 months |
| Azacitidine | Summary of Subgroup Analyses for Kaplan-Meier Estimates for Time to Death From Any Cause | WHO: Other (AML, CMMoL-1 and 2, indeterminate) | 20.46 months |
| Azacitidine | Summary of Subgroup Analyses for Kaplan-Meier Estimates for Time to Death From Any Cause | Gender: Female | 25.11 months |
| Azacitidine | Summary of Subgroup Analyses for Kaplan-Meier Estimates for Time to Death From Any Cause | IPSS: Intermediate 2 | 34.66 months |
| Azacitidine | Summary of Subgroup Analyses for Kaplan-Meier Estimates for Time to Death From Any Cause | IPSS: High | 19.21 months |
| Azacitidine | Summary of Subgroup Analyses for Kaplan-Meier Estimates for Time to Death From Any Cause | Age <65 years | 11.31 months |
| Conventional Care | Summary of Subgroup Analyses for Kaplan-Meier Estimates for Time to Death From Any Cause | IPSS: High | 14.52 months |
| Conventional Care | Summary of Subgroup Analyses for Kaplan-Meier Estimates for Time to Death From Any Cause | Age >= 75 years | 6.20 months |
| Conventional Care | Summary of Subgroup Analyses for Kaplan-Meier Estimates for Time to Death From Any Cause | Gender: Female | 14.85 months |
| Conventional Care | Summary of Subgroup Analyses for Kaplan-Meier Estimates for Time to Death From Any Cause | IPSS: Intermediate 2 | 16.89 months |
| Conventional Care | Summary of Subgroup Analyses for Kaplan-Meier Estimates for Time to Death From Any Cause | Age <65 years | 7.87 months |
| Conventional Care | Summary of Subgroup Analyses for Kaplan-Meier Estimates for Time to Death From Any Cause | Age >= 65 years | 13.87 months |
| Conventional Care | Summary of Subgroup Analyses for Kaplan-Meier Estimates for Time to Death From Any Cause | Gender: Male | 15.02 months |
| Conventional Care | Summary of Subgroup Analyses for Kaplan-Meier Estimates for Time to Death From Any Cause | FAB: Refractory anemia with excess blasts (RAEB) | 15.21 months |
| Conventional Care | Summary of Subgroup Analyses for Kaplan-Meier Estimates for Time to Death From Any Cause | FAB: RAEB in transformation | 15.25 months |
| Conventional Care | Summary of Subgroup Analyses for Kaplan-Meier Estimates for Time to Death From Any Cause | WHO: RAEB 1 | 6.72 months |
| Conventional Care | Summary of Subgroup Analyses for Kaplan-Meier Estimates for Time to Death From Any Cause | WHO: RAEB 2 | 15.02 months |
| Conventional Care | Summary of Subgroup Analyses for Kaplan-Meier Estimates for Time to Death From Any Cause | WHO: Other (AML, CMMoL-1 and 2, indeterminate) | 15.25 months |
Comparison: Age \< 65 years The Kaplan-Meier median time to death was not reached due to a small number of events, so the KM 25th percentile survival time is presented.~Some of the values in outcome table #2 do not have 95% CI values so no 95% CI ranges are contained in the table. Those 95% CI ranges are added here.~Azacitidine: low range of 7.1 months and high range of 15.6 months.~Conventional Care: low range of 4.4 and high range of 12.4 months.p-value: 0.3973Log Rank
Comparison: Age \>= 65 years~Some of the values in outcome table #2 do not have 95% CI values so no 95% CI ranges are contained in the table. Those 95% CI ranges are added here.~Azacitidine: low range of 17.1 months and high range of 34.7 months.~Conventional Care: low range of 8.8 and high range of 16.4 months.p-value: <0.0001Log Rank
Comparison: Age \>= 75 years. The Kaplan-Meier median time to death was not reached due to a small number of events, so the KM 25th percentile survival time is presented.~Some of the values in outcome table #2 do not have 95% CI values so no 95% CI ranges are contained in the table. Those 95% CI ranges are added here.~Azacitidine: low range of 1.7 months and high range of 15.0 months.~Conventional Care: low range of 4.1 and high range of 7.6 months.p-value: 0.0707Log Rank
Comparison: Gender: Male~Some of the values in outcome table #2 do not have 95% CI values so no 95% CI ranges are contained in the table. Those 95% CI ranges are added here.~Azacitidine: low range of 17.9 months and high range of 'does not exist'.~Conventional Care: low range of 10.8 and high range of 17.2 months.p-value: 0.0042Log Rank
Comparison: Gender: Female~Some of the values in outcome table #2 do not have 95% CI values so no 95% CI ranges are contained in the table. Those 95% CI ranges are added here.~Azacitidine: low range of 13.0 months and high range of 'does not exist'.~Conventional Care: low range of 8.2 and high range of 17.6 months.p-value: 0.0469Log Rank
Comparison: FAB: Refractory anemia with excess blasts (RAEB). All patients were stratified at randomization by FAB classification and IPSS score as determined by the investigator using centrally read bone marrow and cytogenetic data. Subsequently, the FAB classifications and IPSS scores were reviewed by an Independent Review Committee (IRC). The subgroup analyses presented by FAB and IPSS represent the FAB classification and IPSS scores as determined by the IRC.p-value: 0.0056Log Rank
Comparison: FAB: RAEB in transformation~Some of the values in outcome table #2 do not have 95% CI values so no 95% CI ranges are contained in the table. Those 95% CI ranges are added here.~Azacitidine: low range of 11.7 months and high range of 'does not exist'.~Conventional Care: low range of 9.4 and high range of 17.0 months.p-value: 0.0322Log Rank
Comparison: WHO: RAEB 1. The Kaplan-Meier median time to death was not reached due to a small number of events, so the KM 25th percentile survival time is presented.~Some of the values in outcome table #2 do not have 95% CI values so no 95% CI ranges are contained in the table. Those 95% CI ranges are added here.~Azacitidine: low range of 6.6 months and high range of 'does not exist'.~Conventional Care: low range of 1.8 and high range of 9.8 months.p-value: 0.1679Log Rank
Comparison: WHO: RAEB-2~Some of the values in outcome table #2 do not have 95% CI values so no 95% CI ranges are contained in the table. Those 95% CI ranges are added here.~Azacitidine: low range of 15.9 months and high range of 'does not exist'.~Conventional Care: low range of 8.8 and high range of 19.4 months.p-value: 0.0692Log Rank
Comparison: WHO: Other~Some of the values in outcome table #2 do not have 95% CI values so no 95% CI ranges are contained in the table. Those 95% CI ranges are added here.~Azacitidine: low range of 15.6 months and high range of 'does not exist'.~Conventional Care: low range of 11.1 and high range of 17.5 months.p-value: 0.0017Log Rank
Comparison: IPSS: Intermediate 2 All patients were stratified at randomization by FAB classification and IPSS score as determined by the investigator using centrally read bone marrow and cytogenetic data. Subsequently, the FAB classifications and IPSS scores were reviewed by an Independent Review Committee (IRC). The subgroup analyses presented by FAB and IPSS represent the FAB classification and IPSS scores as determined by the IRC.p-value: 0.103Log Rank
Comparison: IPSS: High All patients were stratified at randomization by FAB classification and IPSS score as determined by the investigator using centrally read bone marrow and cytogenetic data. Subsequently, the FAB classifications and IPSS scores were reviewed by an Independent Review Committee (IRC). The subgroup analyses presented by FAB and IPSS represent the FAB classification and IPSS scores as determined by the IRC.p-value: 0.002Log Rank
Secondary
Duration of Any Hematologic Improvement
The duration of improvement was defined as the time from the date of hematologic improvement until the date of first documented progression or relapse after hematologic improvement or death from any cause.
Time frame: Day 1 (randomization) to 42 months
Population: Intent to treat population. Participants showing hematologic improvement were 48 in azacitidine and 31 in conventional care.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Azacitidine | Duration of Any Hematologic Improvement | 13.57 months |
| Conventional Care | Duration of Any Hematologic Improvement | 5.18 months |
p-value: 0.0002Log Rank
Secondary
Kaplan-Meier Estimate for Median Time to Transformation to Acute Myeloid Leukemia (AML) or Death From Any Cause, Whichever Occurred First
The time to transformation to AML or death from any cause (whichever occurred first) was defined as the number of days from the date of randomization until the date of documented AML transformation or death from any cause. Patients who did not transform to AML or die were censored at the date of last follow-up.
Time frame: Day 1 (randomization) to 42 months
Population: Intent to treat population. Participants who either transformed to AML or died are 120 for azacitidine and 132 for conventional care. Remaining participants were censored.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Azacitidine | Kaplan-Meier Estimate for Median Time to Transformation to Acute Myeloid Leukemia (AML) or Death From Any Cause, Whichever Occurred First | 13.02 months |
| Conventional Care | Kaplan-Meier Estimate for Median Time to Transformation to Acute Myeloid Leukemia (AML) or Death From Any Cause, Whichever Occurred First | 7.61 months |
p-value: 0.0025Log Rank
p-value: 0.002795% CI: [0.53, 0.87]Regression, Cox
Secondary
Kaplan-Meier Estimates for Median Time to Transformation to Acute Myeloid Leukemia (AML)
The time to transformation to AML was defined as the number of days from the date of randomization until the date of documented AML transformation, defined as a bone marrow blast count ≥ 30% independent of baseline bone marrow count. Patients who did not transform to AML were censored at the date of last follow-up or date of death.
Time frame: Day 1 (randomization) to 42 months
Population: Intent to treat population. Participants who were transformed to AML are 78 for azacitidine and 71 for conventional care. Remaining participants were censored based on the last bone marrow assessment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Azacitidine | Kaplan-Meier Estimates for Median Time to Transformation to Acute Myeloid Leukemia (AML) | 20.66 months |
| Conventional Care | Kaplan-Meier Estimates for Median Time to Transformation to Acute Myeloid Leukemia (AML) | 15.44 months |
p-value: 0.2555Log Rank
p-value: 0.256295% CI: [0.6, 1.15]Regression, Cox
Secondary
Number of Infections Per Treatment Year Requiring Intravenous Antibiotics, Antifungals or Antivirals
The on-treatment adverse event rate of infection requiring IV antibiotics, antifungals, or antivirals per patient-years. The on-treatment period was considered the period from the date of randomization to the last treatment study visit.
Time frame: Day 1 (randomization) to 42 months
Population: Intent to treat population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Azacitidine | Number of Infections Per Treatment Year Requiring Intravenous Antibiotics, Antifungals or Antivirals | 0.16 infections per treatment year |
| Conventional Care | Number of Infections Per Treatment Year Requiring Intravenous Antibiotics, Antifungals or Antivirals | 0.24 infections per treatment year |
p-value: 0.132795% CI: [0.35, 1.2]exact binomial
Secondary
Number of Participants Considered Hematologic Responders by Investigator Determinations Using International Working Group (IWG 2000) Criteria for Myelodysplastic Syndrome (MDS)
Investigator determined responses followed IWG criteria for * complete remission(CR): repeat bone marrow show \<5% myeloblasts, and peripheral blood evaluations lasting \>=2 months of hemoglobin(\>110 g/L), neutrophils(\>=1.5x10\^9/L), platelets(\>=100x10\^9/L), blasts (0%) and no dysplasia * partial remission(PR) is the same as CR for peripheral blood: bone marrow shows blasts decrease by \>=50% or a less advanced FAB classification from pretreatment * stable disease(SD) is a failure to achieve at least a partial remission, but with no evidence of progression for at least 2 months.
Time frame: Day 1 to 42 months
Population: Intent to treat population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Azacitidine | Number of Participants Considered Hematologic Responders by Investigator Determinations Using International Working Group (IWG 2000) Criteria for Myelodysplastic Syndrome (MDS) | Overall (Complete + Partial Remission) | 51 participants |
| Azacitidine | Number of Participants Considered Hematologic Responders by Investigator Determinations Using International Working Group (IWG 2000) Criteria for Myelodysplastic Syndrome (MDS) | Complete Remission | 30 participants |
| Azacitidine | Number of Participants Considered Hematologic Responders by Investigator Determinations Using International Working Group (IWG 2000) Criteria for Myelodysplastic Syndrome (MDS) | Partial Remission | 21 participants |
| Azacitidine | Number of Participants Considered Hematologic Responders by Investigator Determinations Using International Working Group (IWG 2000) Criteria for Myelodysplastic Syndrome (MDS) | Stable Disease | 75 participants |
| Conventional Care | Number of Participants Considered Hematologic Responders by Investigator Determinations Using International Working Group (IWG 2000) Criteria for Myelodysplastic Syndrome (MDS) | Stable Disease | 65 participants |
| Conventional Care | Number of Participants Considered Hematologic Responders by Investigator Determinations Using International Working Group (IWG 2000) Criteria for Myelodysplastic Syndrome (MDS) | Overall (Complete + Partial Remission) | 21 participants |
| Conventional Care | Number of Participants Considered Hematologic Responders by Investigator Determinations Using International Working Group (IWG 2000) Criteria for Myelodysplastic Syndrome (MDS) | Partial Remission | 7 participants |
| Conventional Care | Number of Participants Considered Hematologic Responders by Investigator Determinations Using International Working Group (IWG 2000) Criteria for Myelodysplastic Syndrome (MDS) | Complete Remission | 14 participants |
Comparison: Overall (Complete + Partial Remission)p-value: 0.0001Fisher Exact
Comparison: Complete remissionp-value: 0.015Fisher Exact
Comparison: Partial Remissionp-value: 0.0094Fisher Exact
Comparison: Stable Diseasep-value: 0.3297Fisher Exact
Secondary
Number of Participants in Different Categories of Adverse Experiences During Core Study Period
Patient counts for a variety of subsets of adverse experiences for the core study period (day 1 to 42 months). The individual options for Conventional Care Regimens (Best Supportive Care Only, Low-Dose Cytarabine, and Standard Chemotherapy) are presented as separate treatments.
Time frame: Day 1 (randomization) to 42 months
Population: Safety population excludes 4 Azacitidine patients, 3 Best Supportive Care Only patients, 5 Low-dose Cytarabine patients, and 6 Standard Chemotherapy patients who were randomized/assigned to those regimens but did not receive treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Azacitidine | Number of Participants in Different Categories of Adverse Experiences During Core Study Period | Patients with >=1 treatment emergent AE (TEAE) | 175 participants |
| Azacitidine | Number of Participants in Different Categories of Adverse Experiences During Core Study Period | Patients w TEAE leading to dose reduction | 20 participants |
| Azacitidine | Number of Participants in Different Categories of Adverse Experiences During Core Study Period | Patients w TEAE leading to discontinued treatment | 22 participants |
| Azacitidine | Number of Participants in Different Categories of Adverse Experiences During Core Study Period | Patients with >=1 treatment related TEAE | 169 participants |
| Azacitidine | Number of Participants in Different Categories of Adverse Experiences During Core Study Period | Patients w TEAE leading to dose interruption | 82 participants |
| Azacitidine | Number of Participants in Different Categories of Adverse Experiences During Core Study Period | Patients with >=1 serious TEAE | 114 participants |
| Azacitidine | Number of Participants in Different Categories of Adverse Experiences During Core Study Period | Patients with >=1 serious treatment related TEAE | 43 participants |
| Conventional Care | Number of Participants in Different Categories of Adverse Experiences During Core Study Period | Patients w TEAE leading to dose reduction | 0 participants |
| Conventional Care | Number of Participants in Different Categories of Adverse Experiences During Core Study Period | Patients with >=1 serious treatment related TEAE | 0 participants |
| Conventional Care | Number of Participants in Different Categories of Adverse Experiences During Core Study Period | Patients with >=1 serious TEAE | 71 participants |
| Conventional Care | Number of Participants in Different Categories of Adverse Experiences During Core Study Period | Patients w TEAE leading to discontinued treatment | 4 participants |
| Conventional Care | Number of Participants in Different Categories of Adverse Experiences During Core Study Period | Patients w TEAE leading to dose interruption | 0 participants |
| Conventional Care | Number of Participants in Different Categories of Adverse Experiences During Core Study Period | Patients with >=1 treatment related TEAE | 1 participants |
| Conventional Care | Number of Participants in Different Categories of Adverse Experiences During Core Study Period | Patients with >=1 treatment emergent AE (TEAE) | 97 participants |
| Low-dose Cytarabine | Number of Participants in Different Categories of Adverse Experiences During Core Study Period | Patients with >=1 serious treatment related TEAE | 13 participants |
| Low-dose Cytarabine | Number of Participants in Different Categories of Adverse Experiences During Core Study Period | Patients with >=1 treatment emergent AE (TEAE) | 44 participants |
| Low-dose Cytarabine | Number of Participants in Different Categories of Adverse Experiences During Core Study Period | Patients with >=1 treatment related TEAE | 34 participants |
| Low-dose Cytarabine | Number of Participants in Different Categories of Adverse Experiences During Core Study Period | Patients with >=1 serious TEAE | 27 participants |
| Low-dose Cytarabine | Number of Participants in Different Categories of Adverse Experiences During Core Study Period | Patients w TEAE leading to discontinued treatment | 6 participants |
| Low-dose Cytarabine | Number of Participants in Different Categories of Adverse Experiences During Core Study Period | Patients w TEAE leading to dose reduction | 2 participants |
| Low-dose Cytarabine | Number of Participants in Different Categories of Adverse Experiences During Core Study Period | Patients w TEAE leading to dose interruption | 12 participants |
| Standard Chemotherapy | Number of Participants in Different Categories of Adverse Experiences During Core Study Period | Patients with >=1 serious TEAE | 14 participants |
| Standard Chemotherapy | Number of Participants in Different Categories of Adverse Experiences During Core Study Period | Patients w TEAE leading to dose interruption | 0 participants |
| Standard Chemotherapy | Number of Participants in Different Categories of Adverse Experiences During Core Study Period | Patients w TEAE leading to dose reduction | 0 participants |
| Standard Chemotherapy | Number of Participants in Different Categories of Adverse Experiences During Core Study Period | Patients with >=1 treatment related TEAE | 19 participants |
| Standard Chemotherapy | Number of Participants in Different Categories of Adverse Experiences During Core Study Period | Patients with >=1 treatment emergent AE (TEAE) | 19 participants |
| Standard Chemotherapy | Number of Participants in Different Categories of Adverse Experiences During Core Study Period | Patients w TEAE leading to discontinued treatment | 2 participants |
| Standard Chemotherapy | Number of Participants in Different Categories of Adverse Experiences During Core Study Period | Patients with >=1 serious treatment related TEAE | 13 participants |
Secondary
Number of Participants Showing Hematologic Improvement Using International Working Group (IWG 2000) Criteria for Myelodysplastic Syndrome (MDS) Assessed by Independent Review Committee
IWG 2000 Criteria: Pretreatment=hemoglobin \<100g/L or RBC transfusion-dependent, platelet count \<100x10\^9/L or platelet transfusion dependent, absolute neutrophil count \<1.5x10\^9/L. Erythroid response: Major-\>20g/L increase or transfusion independent. Minor- 10-20g/L increase or \>=50% decrease in transfusion requirements. Platelet response: Major-absolute increase of \>=30x10\^9/L or platelet transfusion independence. Minor-\>=50% increase. Neutrophil response: Major-\>=100% increase or an absolute increase of \>0.5x10\^9/L. Minor-\>=100% increase and absolute increase of \<0.5x10\^9/L.
Time frame: Day 1 to 42 months
Population: Intent to treat population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Azacitidine | Number of Participants Showing Hematologic Improvement Using International Working Group (IWG 2000) Criteria for Myelodysplastic Syndrome (MDS) Assessed by Independent Review Committee | Erythroid Response - Minor n=157, 160 | 2 participants |
| Azacitidine | Number of Participants Showing Hematologic Improvement Using International Working Group (IWG 2000) Criteria for Myelodysplastic Syndrome (MDS) Assessed by Independent Review Committee | Platelet Response - Minor n=138, 127 | 6 participants |
| Azacitidine | Number of Participants Showing Hematologic Improvement Using International Working Group (IWG 2000) Criteria for Myelodysplastic Syndrome (MDS) Assessed by Independent Review Committee | Erythroid Response - Major n=157, 160 | 62 participants |
| Azacitidine | Number of Participants Showing Hematologic Improvement Using International Working Group (IWG 2000) Criteria for Myelodysplastic Syndrome (MDS) Assessed by Independent Review Committee | Neutrophil Response - Major n=131, 111 | 25 participants |
| Azacitidine | Number of Participants Showing Hematologic Improvement Using International Working Group (IWG 2000) Criteria for Myelodysplastic Syndrome (MDS) Assessed by Independent Review Committee | Platelet Response - Major n=141, 129 | 46 participants |
| Azacitidine | Number of Participants Showing Hematologic Improvement Using International Working Group (IWG 2000) Criteria for Myelodysplastic Syndrome (MDS) Assessed by Independent Review Committee | Neutrophil Response - Minor n=131, 111 | 5 participants |
| Azacitidine | Number of Participants Showing Hematologic Improvement Using International Working Group (IWG 2000) Criteria for Myelodysplastic Syndrome (MDS) Assessed by Independent Review Committee | Any Improvement n=177, 178 | 87 participants |
| Conventional Care | Number of Participants Showing Hematologic Improvement Using International Working Group (IWG 2000) Criteria for Myelodysplastic Syndrome (MDS) Assessed by Independent Review Committee | Neutrophil Response - Minor n=131, 111 | 9 participants |
| Conventional Care | Number of Participants Showing Hematologic Improvement Using International Working Group (IWG 2000) Criteria for Myelodysplastic Syndrome (MDS) Assessed by Independent Review Committee | Any Improvement n=177, 178 | 51 participants |
| Conventional Care | Number of Participants Showing Hematologic Improvement Using International Working Group (IWG 2000) Criteria for Myelodysplastic Syndrome (MDS) Assessed by Independent Review Committee | Erythroid Response - Major n=157, 160 | 17 participants |
| Conventional Care | Number of Participants Showing Hematologic Improvement Using International Working Group (IWG 2000) Criteria for Myelodysplastic Syndrome (MDS) Assessed by Independent Review Committee | Erythroid Response - Minor n=157, 160 | 1 participants |
| Conventional Care | Number of Participants Showing Hematologic Improvement Using International Working Group (IWG 2000) Criteria for Myelodysplastic Syndrome (MDS) Assessed by Independent Review Committee | Platelet Response - Major n=141, 129 | 18 participants |
| Conventional Care | Number of Participants Showing Hematologic Improvement Using International Working Group (IWG 2000) Criteria for Myelodysplastic Syndrome (MDS) Assessed by Independent Review Committee | Platelet Response - Minor n=138, 127 | 4 participants |
| Conventional Care | Number of Participants Showing Hematologic Improvement Using International Working Group (IWG 2000) Criteria for Myelodysplastic Syndrome (MDS) Assessed by Independent Review Committee | Neutrophil Response - Major n=131, 111 | 20 participants |
Comparison: Any Improvementp-value: <0.0001Fisher Exact
Comparison: Erythroid Response - Majorp-value: <0.0001Fisher Exact
Comparison: Erythroid Response - Minorp-value: 0.6203Fisher Exact
Comparison: Platelet Response - Majorp-value: 0.0003Fisher Exact
Comparison: Platelet Response - Minorp-value: 0.7514Fisher Exact
Comparison: Neutrophil Response - Majorp-value: 0.8695Fisher Exact
Comparison: Neutrophil Response - Minorp-value: 0.176Fisher Exact
Secondary
Summary of Participants' Platelet Transfusion Status for Participants Who Were Transfusion Dependent at Baseline
Summary of dependence and independence from platelet transfusion at baseline and during treatment for patients who were dependent at baseline. A patient was considered transfusion independent at baseline if the patient had no transfusions during the 56 days prior to randomization. During study, a patient was considered transfusion independent during the on-treatment period if the patient had no transfusions during any 56 consecutive days or more. Otherwise, the patient was considered transfusion dependent.
Time frame: Day 1 (randomization) to 42 months
Population: Intent to treat population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Azacitidine | Summary of Participants' Platelet Transfusion Status for Participants Who Were Transfusion Dependent at Baseline | Baseline Dependent; On-Treatment Independent | 16 participants |
| Azacitidine | Summary of Participants' Platelet Transfusion Status for Participants Who Were Transfusion Dependent at Baseline | Baseline Dependent; On-Treatment Dependent | 22 participants |
| Conventional Care | Summary of Participants' Platelet Transfusion Status for Participants Who Were Transfusion Dependent at Baseline | Baseline Dependent; On-Treatment Independent | 11 participants |
| Conventional Care | Summary of Participants' Platelet Transfusion Status for Participants Who Were Transfusion Dependent at Baseline | Baseline Dependent; On-Treatment Dependent | 16 participants |
Comparison: The p value is from Fisher's exact test comparing the difference in the azacitidine group and the combined group of CCR regimens among patients who were transfusion dependent at baseline and transfusion independent during the on-treatment periodp-value: 1Fisher Exact
Secondary
Summary of Participants' Platelet Transfusion Status for Participants Who Were Transfusion Independent at Baseline
Summary of dependence and independence from platelet transfusion at baseline and during treatment for patients who were independent at baseline. A patient was considered transfusion independent at baseline if the patient had no transfusions during the 56 days prior to randomization. During study, a patient was considered transfusion independent during the on-treatment period if the patient had no transfusions during any 56 consecutive days or more. Otherwise, the patient was considered transfusion dependent.
Time frame: Day 1 (randomization) to 42 months
Population: Intent to treat population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Azacitidine | Summary of Participants' Platelet Transfusion Status for Participants Who Were Transfusion Independent at Baseline | Baseline Independent; On-Treatment Independent | 126 participants |
| Azacitidine | Summary of Participants' Platelet Transfusion Status for Participants Who Were Transfusion Independent at Baseline | Baseline Independent; On-Treatment Dependent | 15 participants |
| Conventional Care | Summary of Participants' Platelet Transfusion Status for Participants Who Were Transfusion Independent at Baseline | Baseline Independent; On-Treatment Independent | 102 participants |
| Conventional Care | Summary of Participants' Platelet Transfusion Status for Participants Who Were Transfusion Independent at Baseline | Baseline Independent; On-Treatment Dependent | 50 participants |
Comparison: The p value is from Fisher's exact test comparing the difference in the azacitidine group and the combined group of CCR regimens among patients who were transfusion independent at baseline and remained transfusion independent during the on-treatment period.p-value: <0.0001Fisher Exact
Secondary
Summary of Participants' Red Blood Cell (RBC) Transfusion Status for Participants Who Were Transfusion Dependent at Baseline
Summary of dependence and independence from red blood cell (RBC) transfusion at baseline and during treatment, for patients who were dependent at baseline. A patient was considered transfusion independent at baseline if the patient had no transfusions during the 56 days prior to randomization. During study, a patient was considered transfusion independent during the on-treatment period if the patient had no transfusions during any 56 consecutive days or more. Otherwise, the patient was considered transfusion dependent.
Time frame: Day 1 (randomization) to 42 months
Population: Intent to treat population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Azacitidine | Summary of Participants' Red Blood Cell (RBC) Transfusion Status for Participants Who Were Transfusion Dependent at Baseline | Baseline Dependent; On-Treatment Independent | 50 participants |
| Azacitidine | Summary of Participants' Red Blood Cell (RBC) Transfusion Status for Participants Who Were Transfusion Dependent at Baseline | Baseline Dependent; On-Treatment Dependent | 61 participants |
| Conventional Care | Summary of Participants' Red Blood Cell (RBC) Transfusion Status for Participants Who Were Transfusion Dependent at Baseline | Baseline Dependent; On-Treatment Independent | 13 participants |
| Conventional Care | Summary of Participants' Red Blood Cell (RBC) Transfusion Status for Participants Who Were Transfusion Dependent at Baseline | Baseline Dependent; On-Treatment Dependent | 101 participants |
Comparison: The p value is from Fisher's exact test comparing the difference in the azacitidine group and the combined group of CCR regimens among patients who were transfusion dependent at baseline and transfusion independent during the on-treatment period.p-value: <0.0001Fisher Exact
Secondary
Summary of Participants' Red Blood Cell (RBC) Transfusion Status for Participants Who Were Transfusion Independent at Baseline
Summary of dependence and independence from red blood cell (RBC) transfusion at baseline and during treatment, for patients who were independent at baseline. A patient was considered transfusion independent at baseline if the patient had no transfusions during the 56 days prior to randomization. During study, a patient was considered transfusion independent during the on-treatment period if the patient had no transfusions during any 56 consecutive days or more. Otherwise, the patient was considered transfusion dependent.
Time frame: Day 1 (randomization) to 42 months
Population: Intent to treat population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Azacitidine | Summary of Participants' Red Blood Cell (RBC) Transfusion Status for Participants Who Were Transfusion Independent at Baseline | Baseline Independent; On-Treatment Independent | 58 participants |
| Azacitidine | Summary of Participants' Red Blood Cell (RBC) Transfusion Status for Participants Who Were Transfusion Independent at Baseline | Baseline Independent; On-Treatment Dependent | 10 participants |
| Conventional Care | Summary of Participants' Red Blood Cell (RBC) Transfusion Status for Participants Who Were Transfusion Independent at Baseline | Baseline Independent; On-Treatment Independent | 37 participants |
| Conventional Care | Summary of Participants' Red Blood Cell (RBC) Transfusion Status for Participants Who Were Transfusion Independent at Baseline | Baseline Independent; On-Treatment Dependent | 28 participants |
Comparison: The p value is from Fisher's exact test comparing the difference in the azacitidine group and the combined group of CCR regimens among patients who were transfusion independent at baseline and remained transfusion independent during the on-treatment period.p-value: 0.0005Fisher Exact
Secondary
Time to Disease Progression, Relapse After Complete or Partial Remission, or Death From Any Cause
The time to disease progression, relapse after complete or partial remission (CR, PR), or death from any cause was defined as the time from the date of randomization until the first date of documented disease progression, relapse after CR or PR, or death from any cause.
Time frame: Day 1 (randomization) to 42 months
Population: Intent to treat population. The number of participants with disease progression, relapse after remission or death from any cause is 84 for azacitidine and 79 for conventional care. Remaining participants were censored.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Azacitidine | Time to Disease Progression, Relapse After Complete or Partial Remission, or Death From Any Cause | 14.13 months |
| Conventional Care | Time to Disease Progression, Relapse After Complete or Partial Remission, or Death From Any Cause | 8.82 months |
p-value: 0.0466Log Rank
p-value: 0.047495% CI: [0.53, 1]Regression, Cox
Post Hoc
Kaplan-Meier Estimates for Median Time to Transformation to Acute Myeloid Leukemia (AML) Based on the Last Bone Marrow Assessment
A sensitivity analysis of time to transformation to AML during the entire study was performed based on the last bone marrow assessment. Patients were censored based on the last bone marrow assessment.
Time frame: Day 1 (randomization) to 42 months
Population: Intent to treat population. Participants who were transformed to AML are 78 for azacitidine and 71 for conventional care. Remaining participants were censored based on the last bone marrow assessment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Azacitidine | Kaplan-Meier Estimates for Median Time to Transformation to Acute Myeloid Leukemia (AML) Based on the Last Bone Marrow Assessment | 17.80 months |
| Conventional Care | Kaplan-Meier Estimates for Median Time to Transformation to Acute Myeloid Leukemia (AML) Based on the Last Bone Marrow Assessment | 11.48 months |
p-value: <0.0001Log Rank
p-value: <0.000195% CI: [0.35, 0.7]Regression, Cox