Alternative Dosing Regimens of Subcutaneous Azacitidine for Myelodysplastic Syndromes

A Multicenter, Randomized, Open-Label Study Comparing Three Alternative Dosing Regimens of Subcutaneous Azacitidine Plus Best Supportive Care for the Treatment of Myelodysplastic Syndromes

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00102687

Enrollment

151

Registered

2005-02-01

Start date

2005-01-01

Completion date

2008-08-01

Last updated

2019-11-22

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Myelodysplastic Syndromes

Brief summary

The purpose of this study is to determine if azacitidine, combined with Best Supportive Care (BSC), is effective in treating myelodysplastic syndromes (MDS) when given according to a different doses and dosing schedules.

Detailed description

Comparison/Control Interventions: The comparison is azacitidine at different doses and schedules. Duration of Intervention: Treatment lasted for a maximum of 18 cycles, which is up to 24 months.

Interventions

DRUGazacitidine

Azacitidine is administered subcutaneously Total of 18 cycles on treatment or early discontinuation.

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

* Diagnosis of refractory anemia, refractory anemia with ringed sideroblasts and at least one of the following: a)Anemia with hemoglobin \<110g/L and requires at least 1 unit packed red blood cell transfusions every 28 days; b)Thrombocytopenia with platelet counts \<100 x 10\^9/L; or c)Neutropenia with absolute neutrophil count \<1.5 x 10\^9/L. * OR, Refractory anemia with excess blasts or refractory anemia with excess blast in transformation, according to the French-American-British classification system for MDS. * At least 18 years of age. * Have a life expectancy of \>7 months. * 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 the normal (ULN) 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 x ULN. * Have serum creatinine levels less than or equal to 1.5 x ULN.

Exclusion criteria

* Secondary MDS. * Prior treatment with azacitidine. * Any prior history of Acute Myeloid Leukemia (AML). * Malignant or metastatic disease within the previous 12 months. * Uncorrected red cell folate deficiency or vitamin B12 deficiency. * Hepatic tumors. * Radiation, chemotherapy, or cytotoxic therapy for non-MDS conditions in the previous 12 months. * Known or suspected hypersensitivity to azacitidine or mannitol. * Prior transplantation or cytotoxic therapy to treat MDS. Prior use of Revlimid and Thalomid allowed after 30 day washout. * Serious medical illness likely to limit survival to less than or equal to 7 months. * Treatment with androgenic hormones during the previous 14 days * Active viral infection with known human immunodeficiency virus or vial hepatitis Type B or C. * Treatment with other investigational drugs with the previous 30 days.

Design outcomes

Primary

Measure	Time frame	Description
Number of Participants In Best Hematological Response Categories as Determined by the Investigator Using International Working Group 2000 (IWG 2000) Criteria For Myelodysplastic Syndromes (MDS) During the Initial Study Period.	Day 1 (randomization) to 6 months	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)
Number of Participants With Best Hematological Improvement Derived Using International Working Group 2000 (IWG 2000) Criteria for MDS During the Initial Study Period.	Day 1 (randomization) to 6 months	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 With Overall Best Hematologic Response and Hematologic Improvement Based on IWG 2000 Criteria For MDS During the Initial Study Period	Day 1 (randomization) to 6 months	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.
Number of Participants Who Improved or Maintained The Hematologic Response From the Initial Study Period (Based on IWG 2000 Criteria For MDS) During the Maintenance Period	24 months	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.

Secondary

Measure	Time frame	Description
Baseline Platelet Values	Day 1 (randomization)	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.
Change From Baseline in Platelets at the End of Initial Study Period (6 Months)	6 months	The difference between platelet values at the end of the initial study period minus the platelet values at baseline.
Change From Baseline in Platelets at the End of the Maintenance Study Period (Month 24)	24 months	The difference between platelet values at the end of the maintenance study period minus the platelet values at baseline.
Baseline Absolute Neutrophil Count (ANC) Values	Day 1 (randomization)	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.
Change From Baseline in Absolute Neutrophil Count (ANC) at the End of the Maintenance Study Period (Month 24)	24 months	The difference between ANC values at the end of the maintenance study period minus the ANC values at baseline.
Change From Baseline in Absolute Neutrophil Count (ANC) at the End of Initial Study Period (6 Months)	6 months	The difference between ANC values at the end of the initial study period minus the ANC values at baseline.
Platelet Transfusion Status at Baseline and End of Initial Study Period (6 Months)	6 months	Shift table comparing the platelet transfusion status of patients at the end of the initial study period to the transfusion status at baseline.
Red Blood Cell (RBC) Transfusion Status at Baseline and End of Maintenance Study Period (24 Months)	24 months	Shift table comparing the RBC transfusion status of patients at the end of the maintenance study period to the transfusion status at baseline.
Platelet Transfusion Status at Baseline and End of Maintenance Study Period (24 Months)	24 months	Shift table comparing the platelet transfusion status of patients at the end of the maintenance study period to the transfusion status at baseline.
Change From Baseline in the Number of Infections Requiring Treatment With IV Antibiotics Per Treatment Cycle (28 Days) for the Initial Study Period	6 months	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).
Change From Baseline in the Number of Infections Requiring Treatment With IV Antibiotics Per Treatment Cycle (28 Days) for the Maintenance Study Period	24 months	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).
Red Blood Cell (RBC) Transfusion Status at Baseline and End of Initial Study Period (6 Months)	6 months	Shift table comparing the RBC transfusion status of patients at the end of the initial study period to the transfusion status at baseline.
Baseline Hemoglobin Values	Day 1 (randomization)	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.
Change From Baseline in Hemoglobin at End of Initial Study Period (6 Months)	6 months	The difference between hemoglobin values at the end of the initial study period minus the hemoglobin values at baseline.
Change From Baseline in Hemoglobin at the End of the Maintenance Study Period	24 months	The difference between hemoglobin values at the end of the maintenance study period minus the hemoglobin values at baseline.

Countries

United States

Participant flow

Pre-assignment details

One hundred and eighty-four patients were screened.

Participants by arm

Arm	Count
Aza-5 Azacitidine administered subcutaneously at 75mg/m\^2 for 5 days on a 28 day cycle.	50
Aza-5-2-2 Azacitidine administered subcutaneously at 75mg/m\^2 for 5 days with 2 days off, then for an additional 2 days, on a 28 day cycle.	50
Aza-5-2-5 Azacitidine administered subcutaneously at 50mg/m\^2 for 5 days with 2 days off, then for an additional 5 days, on a 28 day cycle.	51
Total	151

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002	FG003	FG004
Initial Period	Adverse Event	4	7	9	0	0
Initial Period	Death	1	1	1	0	0
Initial Period	Failed Treatments (relapse,disease prog)	4	4	2	0	0
Initial Period	Physician Decision	2	9	6	0	0
Initial Period	Protocol Violation	0	0	2	0	0
Initial Period	Sponsor's decision	0	1	1	0	0
Initial Period	Transformation to AML (blast > 30%)	1	3	0	0	0
Initial Period	Withdrawal by Subject	6	3	5	0	0
Maintenance Period	Adverse Event	1	0	0	1	3
Maintenance Period	Death	0	0	0	1	1
Maintenance Period	Failed Treatment (relapse,disease prog)	1	1	1	3	4
Maintenance Period	Physician Decision	1	2	3	0	4
Maintenance Period	Transformation to AML (blast > 30%)	0	1	0	2	0
Maintenance Period	Withdrawal by Subject	4	0	2	3	1

Baseline characteristics

Characteristic	Total	Aza-5-2-5	Aza-5-2-2	Aza-5
Age, Continuous	75.0 years	76.0 years	73.0 years	76.0 years
ECOG Performance Status 0=Fully active	45 Participants	14 Participants	19 Participants	12 Participants
ECOG Performance Status 1=Restricted	84 Participants	29 Participants	23 Participants	32 Participants
ECOG Performance Status 2=Ambulatory/capable of self care	15 Participants	7 Participants	5 Participants	3 Participants
ECOG Performance Status 3=Capable/limited care	7 Participants	1 Participants	3 Participants	3 Participants
FAB Classification AML	0 Participants	0 Participants	0 Participants	0 Participants
FAB Classification CMMoL with <5% blasts	7 Participants	1 Participants	3 Participants	3 Participants
FAB Classification CMMoL with >=5% blasts	4 Participants	1 Participants	1 Participants	2 Participants
FAB Classification CMMoL with missing blasts	5 Participants	3 Participants	2 Participants	0 Participants
FAB Classification Other	0 Participants	0 Participants	0 Participants	0 Participants
FAB Classification RA	65 Participants	21 Participants	22 Participants	22 Participants
FAB Classification RAEB	45 Participants	17 Participants	14 Participants	14 Participants
FAB Classification RAEB-T	4 Participants	1 Participants	1 Participants	2 Participants
FAB Classification RARS	21 Participants	7 Participants	7 Participants	7 Participants
Race/Ethnicity, Customized Asian/Oriental	1 Participants	0 Participants	0 Participants	1 Participants
Race/Ethnicity, Customized Black or African American	6 Participants	2 Participants	4 Participants	0 Participants
Race/Ethnicity, Customized Caucasian	136 Participants	48 Participants	41 Participants	47 Participants
Race/Ethnicity, Customized Hispanic	8 Participants	1 Participants	5 Participants	2 Participants
Race/Ethnicity, Customized Other	0 Participants	0 Participants	0 Participants	0 Participants
Sex: Female, Male Female	53 Participants	14 Participants	22 Participants	17 Participants
Sex: Female, Male Male	98 Participants	37 Participants	28 Participants	33 Participants
Transfusion Dependence - Platelets Not platelet transfusion dependent	144 Participants	50 Participants	48 Participants	46 Participants
Transfusion Dependence - Platelets Platelet transfusion dependent	7 Participants	1 Participants	2 Participants	4 Participants
Transfusion Dependence Status - RBCs Not RBC transfusion dependent	80 Participants	29 Participants	26 Participants	25 Participants
Transfusion Dependence Status - RBCs RBC transfusion dependent	71 Participants	22 Participants	24 Participants	25 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	49 / 50	50 / 50	46 / 48	18 / 22	18 / 21
serious Total, serious adverse events	18 / 50	27 / 50	22 / 48	7 / 22	13 / 21

Outcome results

Primary

Number of Participants In Best Hematological Response Categories as Determined by the Investigator Using International Working Group 2000 (IWG 2000) Criteria For Myelodysplastic Syndromes (MDS) During the Initial Study Period.

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)

Time frame: Day 1 (randomization) to 6 months

Population: Intent to treat population. Patients without a second bone marrow assessment could not be evaluated for hematologic response.~(Outcome Description continued)SD is a failure to achieve at least a PR, but with no evidence of progression for at least 2 months.

Arm	Measure	Group	Value (NUMBER)
Aza-5	Number of Participants In Best Hematological Response Categories as Determined by the Investigator Using International Working Group 2000 (IWG 2000) Criteria For Myelodysplastic Syndromes (MDS) During the Initial Study Period.	Overall Response (CR+PR)	4 participants
Aza-5	Number of Participants In Best Hematological Response Categories as Determined by the Investigator Using International Working Group 2000 (IWG 2000) Criteria For Myelodysplastic Syndromes (MDS) During the Initial Study Period.	Complete remission (CR)	2 participants
Aza-5	Number of Participants In Best Hematological Response Categories as Determined by the Investigator Using International Working Group 2000 (IWG 2000) Criteria For Myelodysplastic Syndromes (MDS) During the Initial Study Period.	Partial remission (PR)	2 participants
Aza-5	Number of Participants In Best Hematological Response Categories as Determined by the Investigator Using International Working Group 2000 (IWG 2000) Criteria For Myelodysplastic Syndromes (MDS) During the Initial Study Period.	Stable disease	22 participants
Aza-5-2-2	Number of Participants In Best Hematological Response Categories as Determined by the Investigator Using International Working Group 2000 (IWG 2000) Criteria For Myelodysplastic Syndromes (MDS) During the Initial Study Period.	Stable disease	19 participants
Aza-5-2-2	Number of Participants In Best Hematological Response Categories as Determined by the Investigator Using International Working Group 2000 (IWG 2000) Criteria For Myelodysplastic Syndromes (MDS) During the Initial Study Period.	Overall Response (CR+PR)	3 participants
Aza-5-2-2	Number of Participants In Best Hematological Response Categories as Determined by the Investigator Using International Working Group 2000 (IWG 2000) Criteria For Myelodysplastic Syndromes (MDS) During the Initial Study Period.	Partial remission (PR)	1 participants
Aza-5-2-2	Number of Participants In Best Hematological Response Categories as Determined by the Investigator Using International Working Group 2000 (IWG 2000) Criteria For Myelodysplastic Syndromes (MDS) During the Initial Study Period.	Complete remission (CR)	2 participants
Aza-5-2-5	Number of Participants In Best Hematological Response Categories as Determined by the Investigator Using International Working Group 2000 (IWG 2000) Criteria For Myelodysplastic Syndromes (MDS) During the Initial Study Period.	Stable disease	20 participants
Aza-5-2-5	Number of Participants In Best Hematological Response Categories as Determined by the Investigator Using International Working Group 2000 (IWG 2000) Criteria For Myelodysplastic Syndromes (MDS) During the Initial Study Period.	Complete remission (CR)	2 participants
Aza-5-2-5	Number of Participants In Best Hematological Response Categories as Determined by the Investigator Using International Working Group 2000 (IWG 2000) Criteria For Myelodysplastic Syndromes (MDS) During the Initial Study Period.	Partial remission (PR)	2 participants
Aza-5-2-5	Number of Participants In Best Hematological Response Categories as Determined by the Investigator Using International Working Group 2000 (IWG 2000) Criteria For Myelodysplastic Syndromes (MDS) During the Initial Study Period.	Overall Response (CR+PR)	4 participants

Primary

Number of Participants Who Improved or Maintained The Hematologic Response From the Initial Study Period (Based on IWG 2000 Criteria For MDS) During the Maintenance Period

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.

Time frame: 24 months

Population: Intent to treat population.

Arm	Measure	Group	Value (NUMBER)
Aza-5	Number of Participants Who Improved or Maintained The Hematologic Response From the Initial Study Period (Based on IWG 2000 Criteria For MDS) During the Maintenance Period	Improved response from initial study period	7 participants
Aza-5	Number of Participants Who Improved or Maintained The Hematologic Response From the Initial Study Period (Based on IWG 2000 Criteria For MDS) During the Maintenance Period	Maintained response from initial study period	6 participants
Aza-5-2-2	Number of Participants Who Improved or Maintained The Hematologic Response From the Initial Study Period (Based on IWG 2000 Criteria For MDS) During the Maintenance Period	Improved response from initial study period	10 participants
Aza-5-2-2	Number of Participants Who Improved or Maintained The Hematologic Response From the Initial Study Period (Based on IWG 2000 Criteria For MDS) During the Maintenance Period	Maintained response from initial study period	5 participants
Aza-5-2-5	Number of Participants Who Improved or Maintained The Hematologic Response From the Initial Study Period (Based on IWG 2000 Criteria For MDS) During the Maintenance Period	Improved response from initial study period	12 participants
Aza-5-2-5	Number of Participants Who Improved or Maintained The Hematologic Response From the Initial Study Period (Based on IWG 2000 Criteria For MDS) During the Maintenance Period	Maintained response from initial study period	10 participants

Primary

Number of Participants With Best Hematological Improvement Derived Using International Working Group 2000 (IWG 2000) Criteria for MDS During the Initial Study Period.

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)

Time frame: Day 1 (randomization) to 6 months

Population: Intent to treat population. Patients count only once for best response within an improvement category.~(Outcome Description continued) Neutrophil response: Major-\>=100% increase in neutrophil count or an absolute increase of \>0.5x10\^9/L. Minor-\>=100% increase but an absolute increase of \<0.5x10\^9/L.

Arm	Measure	Group	Value (NUMBER)
Aza-5	Number of Participants With Best Hematological Improvement Derived Using International Working Group 2000 (IWG 2000) Criteria for MDS During the Initial Study Period.	Erythroid response - Major n=44,43,41	18 participants
Aza-5	Number of Participants With Best Hematological Improvement Derived Using International Working Group 2000 (IWG 2000) Criteria for MDS During the Initial Study Period.	Platelet response - Minor n=24,28,28	2 participants
Aza-5	Number of Participants With Best Hematological Improvement Derived Using International Working Group 2000 (IWG 2000) Criteria for MDS During the Initial Study Period.	Platelet response - Major n=24,28,28	10 participants
Aza-5	Number of Participants With Best Hematological Improvement Derived Using International Working Group 2000 (IWG 2000) Criteria for MDS During the Initial Study Period.	Any Improvement n=50,49,47	29 participants
Aza-5	Number of Participants With Best Hematological Improvement Derived Using International Working Group 2000 (IWG 2000) Criteria for MDS During the Initial Study Period.	Neutrophil response - Minor n=24,22,16	2 participants
Aza-5	Number of Participants With Best Hematological Improvement Derived Using International Working Group 2000 (IWG 2000) Criteria for MDS During the Initial Study Period.	Neutrophil response - Major n=24,22,16	4 participants
Aza-5	Number of Participants With Best Hematological Improvement Derived Using International Working Group 2000 (IWG 2000) Criteria for MDS During the Initial Study Period.	Erythroid response - Minor n=44,43,41	4 participants
Aza-5-2-2	Number of Participants With Best Hematological Improvement Derived Using International Working Group 2000 (IWG 2000) Criteria for MDS During the Initial Study Period.	Platelet response - Major n=24,28,28	11 participants
Aza-5-2-2	Number of Participants With Best Hematological Improvement Derived Using International Working Group 2000 (IWG 2000) Criteria for MDS During the Initial Study Period.	Any Improvement n=50,49,47	20 participants
Aza-5-2-2	Number of Participants With Best Hematological Improvement Derived Using International Working Group 2000 (IWG 2000) Criteria for MDS During the Initial Study Period.	Erythroid response - Major n=44,43,41	15 participants
Aza-5-2-2	Number of Participants With Best Hematological Improvement Derived Using International Working Group 2000 (IWG 2000) Criteria for MDS During the Initial Study Period.	Erythroid response - Minor n=44,43,41	1 participants
Aza-5-2-2	Number of Participants With Best Hematological Improvement Derived Using International Working Group 2000 (IWG 2000) Criteria for MDS During the Initial Study Period.	Platelet response - Minor n=24,28,28	0 participants
Aza-5-2-2	Number of Participants With Best Hematological Improvement Derived Using International Working Group 2000 (IWG 2000) Criteria for MDS During the Initial Study Period.	Neutrophil response - Major n=24,22,16	3 participants
Aza-5-2-2	Number of Participants With Best Hematological Improvement Derived Using International Working Group 2000 (IWG 2000) Criteria for MDS During the Initial Study Period.	Neutrophil response - Minor n=24,22,16	0 participants
Aza-5-2-5	Number of Participants With Best Hematological Improvement Derived Using International Working Group 2000 (IWG 2000) Criteria for MDS During the Initial Study Period.	Platelet response - Minor n=24,28,28	0 participants
Aza-5-2-5	Number of Participants With Best Hematological Improvement Derived Using International Working Group 2000 (IWG 2000) Criteria for MDS During the Initial Study Period.	Erythroid response - Major n=44,43,41	18 participants
Aza-5-2-5	Number of Participants With Best Hematological Improvement Derived Using International Working Group 2000 (IWG 2000) Criteria for MDS During the Initial Study Period.	Neutrophil response - Minor n=24,22,16	0 participants
Aza-5-2-5	Number of Participants With Best Hematological Improvement Derived Using International Working Group 2000 (IWG 2000) Criteria for MDS During the Initial Study Period.	Neutrophil response - Major n=24,22,16	3 participants
Aza-5-2-5	Number of Participants With Best Hematological Improvement Derived Using International Working Group 2000 (IWG 2000) Criteria for MDS During the Initial Study Period.	Platelet response - Major n=24,28,28	10 participants
Aza-5-2-5	Number of Participants With Best Hematological Improvement Derived Using International Working Group 2000 (IWG 2000) Criteria for MDS During the Initial Study Period.	Erythroid response - Minor n=44,43,41	2 participants
Aza-5-2-5	Number of Participants With Best Hematological Improvement Derived Using International Working Group 2000 (IWG 2000) Criteria for MDS During the Initial Study Period.	Any Improvement n=50,49,47	26 participants

Primary

Number of Participants With Overall Best Hematologic Response and Hematologic Improvement Based on IWG 2000 Criteria For MDS During the Initial Study Period

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.

Time frame: Day 1 (randomization) to 6 months