Alternative Dosing Regimens of Subcutaneous Azacitidine for Myelodysplastic Syndromes

Participant counts by best hematological response; complete remission(CR) is better than a partial remission(PR) which is better than stable disease(SD).

Investigator determined responses followed IWG 2000 criteria for MDS 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 PR is the same as CR for peripheral blood: bone marrow shows blasts decrease by >=50% or a less advanced FAB classification from pretreatment (see Population Descrip)

IWG 2000 Criteria: Pretreatment=hemoglobin <110g/L or RBC transfusion-dependence, platelet count <100x10^9/L or platelet transfusion dependence, absolute neutrophil count <1.5x10^9/L.

Erythroid response: Major->20g/L increase in hemoglobin or transfusion independence. Minor- 10-20g/L increase in hemoglobin or >=50% decrease in transfusion requirements.

Platelet response: Major-absolute increase of platelet count by >=30x10^9/L or platelet transfusion independence. Minor->=50% increase in platelet count with net increase >10x10^9/L but <30x10^9/L.

(continued in Population Description)

Number of participants whose best hematological outcome was either complete remission (CR), partial remission (PR) (as determined by the investigator), or any hematologic improvement (based on the IWG 2000 criteria for MDS). See previous outcomes for detailed definitions.

Hematologic response during the maintenance period are compared to the response in the initial study period. Initial response could have been a complete remission, a partial remission, stable disease or a hematologic improvement. Maintenance period best response is after randomization to a maintenance arm for those randomized, and is after the start of cycle 7 for those remaining on initial period treatment throughout the study.

The median values for hemoglobin based on blood tests performed on study day 1 (prior to study treatment) constitute a baseline measure for hemoglobin. Baseline values are used to compare to values following treatment.

The difference between hemoglobin values at the end of the initial study period minus the hemoglobin values at baseline.

The difference between hemoglobin values at the end of the maintenance study period minus the hemoglobin values at baseline.

The median values for platelets based on blood tests performed on study day 1 (prior to study treatment) constitute a baseline measure for platelets. Baseline values are used to compare to values following treatment.

The difference between platelet values at the end of the initial study period minus the platelet values at baseline.

The difference between platelet values at the end of the maintenance study period minus the platelet values at baseline.

The median values for ANC based on blood tests performed on study day 1 (prior to study treatment) constitute a baseline measure for ANC. Baseline values are used to compare to values following treatment.

The difference between ANC values at the end of the initial study period minus the ANC values at baseline.

The difference between ANC values at the end of the maintenance study period minus the ANC values at baseline.

Shift table comparing the RBC transfusion status of patients at the end of the initial study period to the transfusion status at baseline.

Shift table comparing the platelet transfusion status of patients at the end of the initial study period to the transfusion status at baseline.

Shift table comparing the RBC transfusion status of patients at the end of the maintenance study period to the transfusion status at baseline.

Shift table comparing the platelet transfusion status of patients at the end of the maintenance study period to the transfusion status at baseline.

Baseline uses the average number of infections requiring IV antibiotic treatment from the 28 days prior to and including the day of first dose to an initial treatment arm. Initial study period values total the number of infections requiring IV antibiotic treatment divided by the number of treatment cycles (each cycle is approximately one month).

Baseline uses the average number of infections requiring IV antibiotic treatment from the 28 days prior to and including the day of first dose to an initial treatment arm. Maintenance study period values total the number of infections requiring IV antibiotic treatment divided by the number of treatment cycles (each cycle is approximately one month).