A Survival Study in Patients With High Risk Myelodysplastic Syndromes Comparing Azacitidine Versus Conventional Care

Sponsor

Celgene (Industry)

Overall Status

Completed

CT.gov ID

NCT00071799

Collaborator

(none)

358

Enrollment

108

Locations

Arms

Actual Duration (Months)

3.3

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Myelodysplastic Syndromes	Drug: Azacitidine Other: Physician Choice	Phase 3

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

358 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Other

Official Title:

A Multicenter, Randomized, Open-label, Parallel-group, Phase 3 Trial of Subcutaneous Azacitidine Plus Best Supportive Care Versus Conventional Care Regimens Plus Best Supportive Care for the Treatment of Myelodysplastic Syndromes (MDS)

Actual Study Start Date :

Nov 1, 2003

Actual Primary Completion Date :

Jul 1, 2007

Actual Study Completion Date :

Jul 1, 2007

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Azacitidine Study Drug plus best supportive care. Treatment with erythropoietin was not permitted	Drug: Azacitidine 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. Other Names: AZA
Active Comparator: Conventional Care Physician choice of low dose cytarabine (plus best supportive care), standard chemotherapy (plus best supportive care) or best supportive care (only). Treatment with erythropoietin was not permitted	Other: Physician 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 Other Names: cytarabine anthracycline

Arm

Intervention/Treatment

Experimental: Azacitidine

Study Drug plus best supportive care. Treatment with erythropoietin was not permitted

Drug: Azacitidine

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.

Other Names:

AZA

Active Comparator: Conventional Care

Physician choice of low dose cytarabine (plus best supportive care), standard chemotherapy (plus best supportive care) or best supportive care (only). Treatment with erythropoietin was not permitted

Other: Physician 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

Other Names:

cytarabine

anthracycline

Outcome Measures

Primary Outcome Measures

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 Outcome Measures

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.
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.
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.
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.
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama School of Medicine	Birmingham	Alabama	United States	35294
2	Indiana University Cancer Center	Indianapolis	Indiana	United States	46202
3	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
4	Mount Sinai Medical Center	New York	New York	United States	10029-6574
5	Case Western Reserve University	Cleveland	Ohio	United States	44106
6	Oregon Cancer Center	Portland	Oregon	United States	97201
7	Western Pennsylvania Cancer Institute	Pittsburgh	Pennsylvania	United States	15224
8	Froedtert Memorial Lutheran Hospital	Milwaukee	Wisconsin	United States	53226
9	Liverpool Hospital	Liverpool	New South Wales	Australia	2170
10	Royal North Shore Hospital	St. Leonards	New South Wales	Australia	2065
11	The Newcastle Mater Miseriecordiae Hospital	Warratah	New South Wales	Australia	2298
12	Royal Brisbane Hospital	Hersten	Queensland	Australia	4029
13	Princess Alexandra Hospital	Woolloongabba	Queensland	Australia	4102
14	Royal Adelaide Hospital	Adelaide	South Australia	Australia	5000
15	Peter MacCallum Cancer Institute	East Melbourne	Victoria	Australia	3002
16	Royal Melbourne Hospital	Melbourne	Victoria	Australia	3050
17	The Alfred Hospital	Melbourne	Victoria	Australia	3181
18	The Royal Perth Hospital	Perth	Western Australia	Australia	6847
19	First Clinical Base - Clinic of Hematology, MHAT - Pleven	Pleven		Bulgaria	5800
20	MHAT "St George" Clinic of Hematology, Plovdiv	Plovdiv		Bulgaria	4002
21	III-rd Internal Department, District Dispensary for Oncology diseases with stationary(DDOncDIU)	Plovdiv		Bulgaria	4004
22	National Centre of Hematology and Transfusiology, Sofia	Sofia		Bulgaria	1756
23	Multiprofile Hospital for Active Treatment (MHAT), "St. Marina" Clinic of Hematology	Varna		Bulgaria	3010
24	University Multiprofile Hospital for Active Treatment "Sveta Marina"	Varna		Bulgaria	9010
25	Fakultni nemocnice Brno	Jihlavska	Brno	Czechia	639 00
26	Fakultni nemocnice Hradec Kralove	Sokolska	Hradec Kralove	Czechia	500 05
27	Fakultni Nemocnice Olomouc	Olomouc		Czechia	775 20
28	Vseobecna Fakultni Nemocnice	Praha		Czechia	2 128 08
29	Uslav Hematologie a Krevni Transfuze	Praha		Czechia	2 128 20
30	Chu D'Angers	Angers		France	49033
31	Hopital Beaujon	Clichy		France	92110
32	Che De Lille	Lille		France	59037
33	Hospital Edouard Herriot	Lyon		France	69437
34	Institute Paoli Calmettes	Marseille		France	13009
35	Chu De Nantes	Nantes		France	44093
36	Hospital Saint Louis	Paris		France	75010
37	Hopital Cochin	Paris		France	75679
38	Centre Henri Becquerel	Rouen		France	76038
39	Chu Purpan	Toulouse		France	31059
40	Universitatsklinikum Benjamin Franklin	Hindenburgdamm	Berlin	Germany	D-12203
41	Universitatsklinikum Bonn	Bonn		Germany	53105
42	Klinikum Chemnitz gGmbH	Chemnitz		Germany	9113
43	Universitatsklinikum Carl Gustav Carus	Dresden		Germany	1307
44	St Johannes Hospital	Duisburg		Germany	47166
45	Heinrich-Heine University Dusseldorf	Dusseldorf		Germany	40225
46	University Essen	Essen		Germany	45147
47	Gerorg-August-Universitat Gottingen	Gottingen		Germany	37075
48	Allgemeines Krankenhaus St. Georg	Hamburg		Germany	D-20099
49	Universitatsklinikum Hambur-Eppendorf	Hamburg		Germany	D-20246
50	Universitatsklinikum Kiel II	Kiel		Germany	D-24116
51	Universitatsklinikum Ulm	Ulm		Germany	89070
52	University Hospital-Attikon	Haidari	Athens	Greece	12462
53	University General Hospital of Heraklio Voutes	Heraklio	Crete	Greece	71110
54	District General Hospital of Athens	Athens		Greece	11527
55	General Hospital of Chest Disease	Athens		Greece	11527
56	University General Hospital of Ioannina	Ioannina		Greece	45500
57	University General Hospital of Patra Rio	Patra		Greece	26500
58	Orszagos Gyogyintezeti Kozpont	Budapest		Hungary	1135
59	University of Pecs, 1st Dept of Internal Medicine	Pecs		Hungary	7624
60	University of Szeged, 2nd Department of Internal Medicine	Szeged		Hungary	6701
61	Policlinico S. Orsola-Malpighi	Bologna		Italy	40138
62	Universita di Firenze	Firenze		Italy	50139
63	Ospedale San Martino	Genova		Italy	I-16132
64	Instituto Nazionale Dei Tumori	Milano		Italy	20133
65	Centro Oncologico Modenese	Modena		Italy	41100
66	Ospedale San Eugenio	Roma		Italy	00144
67	Policlinico Gemelli	Roma		Italy	00168
68	Instituto Nazionale Tumori "Regina Elena"	Roma		Italy	144
69	Ospedale Casa Sollievo Della Sofferenza - Irrc	San Giovanni Rotondo		Italy	71013
70	Universita Degli Studi Di Sassari	Sassari		Italy	7100
71	VU University Medical Center Amsterdam	Amsterdam		Netherlands	1081 HV
72	Univ Hospital St. Radboud	Nijmejen		Netherlands
73	Samodzielny Publiczny Szpital Kliniczny Nr 1	Gdansk		Poland	80-952
74	Wojewodzki Szpital Specjalistyczny	Lodz		Poland	93-510
75	Samodzielny Publiczny Szpital Kliniczny	Lublin		Poland	20081
76	Wojskowy Instytut Medyczny	Warszawa		Poland	00-909
77	Samodzelny Publiczny Centralny Szpital Kliniczny	Warszawa		Poland	02-097
78	Samodzielny Publiczny Szpital Kliniczny Nr 1	Wroclaw		Poland	50-367
79	Burdenko Central Military Clinical Hospital	Moscow		Russian Federation	105299
80	Blokhin Cancer Research Center	Moscow		Russian Federation	115487
81	Scientific Haematology Center, Moscow	Moscow		Russian Federation	125167
82	Institute of Haematology & Blood Transfusion	St. Petersburg		Russian Federation	193024
83	Pavlov State Medical University	St. Petersburg		Russian Federation	197022
84	Pavlov State Medical University	St. Petersburg		Russian Federation	197089
85	City Hospital #31	St. Petersburg		Russian Federation	197110
86	Hospital Santa Creu I Sant Pau	Barcelona		Spain	08025
87	Hospital Clinic	Barcelona		Spain	08036
88	Hospital Universitario Germans Trias I Pujol	Barcelona		Spain
89	Hospital de Leon	Leon		Spain	24071
90	Hospital Universitario De La Princesa	Madrid		Spain	28006
91	Hospital Ramon Y Cajal	Madrid		Spain	28034
92	Hospital La Paz, Madrid	Madrid		Spain	28046
93	Hospital Clinico San Carlos	Madrid		Spain	28048
94	Hospital Son Llatzer	Palma de Mallorca		Spain	07198
95	Hospital Universitario Del Salamanca	Salamanca		Spain	37007
96	Hospital Universitario La Fe	Valencia		Spain	46009
97	Sahlgrenska University Hospital	Goteborg		Sweden	S-413 45
98	Lund Universtiy Hospital	Lund		Sweden	22185
99	University Hospital MAS	Malmo		Sweden	S-205 02
100	Huddinge University Hospital	Stockholm		Sweden	14186
101	Uppsala University Hospital	Uppsala		Sweden	S-751 85
102	Royal Bournemouth General Hospital	Bournemouth		United Kingdom	BH7 7DW
103	St. Bartholomew's Hospital	London		United Kingdom	EC1A 7BE
104	Kings College Hospital NHS Trust	London		United Kingdom
105	Christie Hospital	Manchester		United Kingdom	M20 4BX
106	Norfolk and Norwich University Hospital	Norwich		United Kingdom	NR4 7UY
107	John Radcliffe Hospital	Oxford		United Kingdom	OX3 9DU
108	Royal Cornwall Hospital	Truro		United Kingdom	TR1 3LJ

Sponsors and Collaborators

Celgene

Investigators

Study Director: CL Beach, Celgene Corporation

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

Study record for the extension study of AZA PH GL 2003 CL 001

Publications

None provided.

Responsible Party:

Celgene

ClinicalTrials.gov Identifier:

NCT00071799

Other Study ID Numbers:

AZA PH GL 2003 CL001

First Posted:

Nov 5, 2003

Last Update Posted:

Oct 29, 2019

Last Verified:

Oct 1, 2019

Additional relevant MeSH terms:

Preleukemia

Myelodysplastic Syndromes

Syndrome

Cytarabine

Azacitidine

Study Results

Participant Flow

Recruitment Details
Pre-assignment Detail	738 patients screened from 98 investigator sites. Randomized patients contributed by 79 investigator sites.

Arm/Group Title	Azacitidine	Conventional Care
Arm/Group Description	Azacitidine, 75 mg/m^2/day given by subcutaneous injection for 7 days of every 28 day cycle, plus best supportive care.	Physician choice of low dose cytarabine, standard chemotherapy, or best supportive care (consisting of blood products, growth factors, antibiotics)
Period Title: Overall Study
STARTED	179	179
COMPLETED	109	81
NOT COMPLETED	70	98

Baseline Characteristics

Arm/Group Title	Azacitidine	Conventional Care	Total
Arm/Group Description	Azacitidine, 75 mg/m^2/day given by subcutaneous injection for 7 days of every 28 day cycle, plus best supportive care.	Physician choice of low dose cytarabine, standard chemotherapy, or best supportive care (consisting of blood products, growth factors, antibiotics)	Total of all reporting groups
Overall Participants	179	179	358
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	68.0 (7.57)	69.2 (7.87)	68.6 (7.73)
Sex: Female, Male (Count of Participants)
Female	47 26.3%	60 33.5%	107 29.9%
Male	132 73.7%	119 66.5%	251 70.1%
Race/Ethnicity, Customized (participants) [Number]
Caucasian	177 98.9%	175 97.8%	352 98.3%
Black or African American	0 0%	0 0%	0 0%
Asian/Oriental	2 1.1%	3 1.7%	5 1.4%
Hispanic	0 0%	1 0.6%	1 0.3%
Other	0 0%	0 0%	0 0%
French-American-British (FAB) Classification (participants) [Number]
Refractory anemia with excess blasts (RAEB)	104 58.1%	103 57.5%	207 57.8%
RAEB in transformation	61 34.1%	62 34.6%	123 34.4%
Modified chronic myelomonocytic leukemia	6 3.4%	5 2.8%	11 3.1%
Acute myeloid leukemia	1 0.6%	1 0.6%	2 0.6%
Myeloproliferative disease	4 2.2%	2 1.1%	6 1.7%
Indeterminate	3 1.7%	6 3.4%	9 2.5%
International Prognostic Scoring System (IPSS) (participants) [Number]
Intermediate risk level 1 (0.5-1.0)	5 2.8%	13 7.3%	18 5%
Intermediate risk level 2 (1.5-2.0)	76 42.5%	70 39.1%	146 40.8%
High risk (2.5-3.5)	82 45.8%	85 47.5%	167 46.6%
Not applicable	5 2.8%	3 1.7%	8 2.2%
Indeterminate	11 6.1%	8 4.5%	19 5.3%
World Health Organization (WHO) Classification (participants) [Number]
Refractory anemia with excess blasts - 1	14 7.8%	17 9.5%	31 8.7%
Refractory anemia with excess blasts - 2	98 54.7%	95 53.1%	193 53.9%
Chronic myelomonocytic leukemia - 1 (CMMoL-1)	1 0.6%	0 0%	1 0.3%
Chronic myelomonocytic leukemia - 2 (CMMoL-2)	10 5.6%	5 2.8%	15 4.2%
Acute myeloid leukemia	55 30.7%	58 32.4%	113 31.6%
Indeterminate	1 0.6%	4 2.2%	5 1.4%
Body Surface Area (meters squared) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [meters squared]	1.9 (0.19)	1.8 (0.19)	1.9 (0.19)
Weight (kilograms) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kilograms]	76.5 (14.08)	74.6 (13.58)	75.6 (13.85)

Outcome Measures

1. Primary Outcome

Title	Kaplan-Meier Estimates for Median Time to Death From Any Cause
Description	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

Outcome Measure Data

Analysis Population Description
Intent to treat population. Includes participants who died and participants who were censored.

Arm/Group Title	Azacitidine	Conventional Care
Arm/Group Description	Azacitidine, 75 mg/m^2/day given by subcutaneous injection for 7 days of every 28 day cycle, plus best supportive care.	Physician choice of low dose cytarabine, standard chemotherapy, or best supportive care (consisting of blood products, growth factors, antibiotics)
Measure Participants	179	179
Number [months]	24.46	15.02

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Azacitidine, Conventional Care
	Comments	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.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.0001
	Comments
	Method	Log Rank
	Comments	The p value is two-sided from the log rank test stratified by the randomization stratification factors of IPSS classification and FAB classification.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Azacitidine, Conventional Care
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.0002
	Comments
	Method	Regression, Cox
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.58
	Confidence Interval	(2-Sided) 95% 0.43 to 0.77
	Parameter Dispersion	Type: Value:
	Estimation Comments	Cox proportional hazards model stratified on the randomization factors of FAB and IPSS with model term of treatment.

2. Primary Outcome

Title	Summary of Subgroup Analyses for Kaplan-Meier Estimates for Time to Death From Any Cause
Description	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

Outcome Measure Data

Analysis Population Description
Intent to treat population. Includes participants who died and those who were censored.

Arm/Group Title	Azacitidine	Conventional Care
Arm/Group Description	Azacitidine, 75 mg/m^2/day given by subcutaneous injection for 7 days of every 28 day cycle, plus best supportive care.	Physician choice of low dose cytarabine, standard chemotherapy, or best supportive care (consisting of blood products, growth factors, antibiotics)
Measure Participants	179	179
Age <65 years	11.31	7.87
Age >= 65 years	24.46	13.87
Age >= 75 years	8.92	6.20
Gender: Male	24.46	15.02
Gender: Female	25.11	14.85
FAB: Refractory anemia with excess blasts (RAEB)	34.66	15.21
FAB: RAEB in transformation	17.25	15.25
WHO: RAEB 1	11.54	6.72
WHO: RAEB 2	21.11	15.02
WHO: Other (AML, CMMoL-1 and 2, indeterminate)	20.46	15.25
IPSS: Intermediate 2	34.66	16.89
IPSS: High	19.21	14.52

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Azacitidine, Conventional Care
	Comments	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.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.3973
	Comments	The p value is two-sided from the log rank test stratified by the randomization stratification factors of IPSS classification and FAB classification
	Method	Log Rank
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Azacitidine, Conventional Care
	Comments	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.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	The p value is two-sided from the log rank test stratified by the randomization stratification factors of IPSS classification and FAB classification
	Method	Log Rank
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Azacitidine, Conventional Care
	Comments	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.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.0707
	Comments	The p value is two-sided from the log rank test stratified by the randomization stratification factors of IPSS classification and FAB classification
	Method	Log Rank
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Azacitidine, Conventional Care
	Comments	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.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.0042
	Comments	The p value is two-sided from the log rank test stratified by the randomization stratification factors of IPSS classification and FAB classification
	Method	Log Rank
	Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Azacitidine, Conventional Care
	Comments	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.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.0469
	Comments	The p value is two-sided from the log rank test stratified by the randomization stratification factors of IPSS classification and FAB classification
	Method	Log Rank
	Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Azacitidine, Conventional Care
	Comments	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.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.0056
	Comments	95% CI ranges are added here. Azacitidine: low range of 21.1 months and high range of 'does not exist'. Conventional Care: low range of 9.3 and high range of 21.9 months.
	Method	Log Rank
	Comments	The p value is two-sided from the log rank test stratified by the randomization stratification factors of IPSS classification and FAB classification.

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Azacitidine, Conventional Care
	Comments	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.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.0322
	Comments	The p value is two-sided from the log rank test stratified by the randomization stratification factors of IPSS classification and FAB classification
	Method	Log Rank
	Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Azacitidine, Conventional Care
	Comments	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.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.1679
	Comments	The p value is two-sided from the log rank test stratified by the randomization stratification factors of IPSS classification and FAB classification
	Method	Log Rank
	Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Azacitidine, Conventional Care
	Comments	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.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.0692
	Comments	The p value is two-sided from the log rank test stratified by the randomization stratification factors of IPSS classification and FAB classification
	Method	Log Rank
	Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Azacitidine, Conventional Care
	Comments	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.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.0017
	Comments	The p value is two-sided from the log rank test stratified by the randomization stratification factors of IPSS classification and FAB classification
	Method	Log Rank
	Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Azacitidine, Conventional Care
	Comments	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.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.1030
	Comments	95% CI ranges are added here. Azacitidine: low range of 17.1 months and high range of 'does not exist'. Conventional Care: low range of 8.7 and high range of 24.1 months.
	Method	Log Rank
	Comments	The p value is two-sided from the log rank test stratified by the randomization stratification factors of IPSS classification and FAB classification.

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Azacitidine, Conventional Care
	Comments	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.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.0020
	Comments	95% CI ranges are added here. Azacitidine: low range of 15.0 months and high range of 'does not exist'. Conventional Care: low range of 9.0 and high range of 17.0 months.
	Method	Log Rank
	Comments	The p value is two-sided from the log rank test stratified by the randomization stratification factors of IPSS classification and FAB classification

3. Secondary Outcome

Title	Kaplan-Meier Estimate for Median Time to Transformation to Acute Myeloid Leukemia (AML) or Death From Any Cause, Whichever Occurred First
Description	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

Outcome Measure Data

Analysis Population Description
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/Group Title	Azacitidine	Conventional Care
Arm/Group Description	Azacitidine, 75 mg/m^2/day given by subcutaneous injection for 7 days of every 28 day cycle, plus best supportive care.	Physician choice of low dose cytarabine, standard chemotherapy, or best supportive care (consisting of blood products, growth factors, antibiotics)
Measure Participants	179	179
Median (95% Confidence Interval) [months]	13.02	7.61

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Azacitidine, Conventional Care
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.0025
	Comments	The p value is two-sided from the log rank test stratified by the randomization stratification factors of IPSS classification and FAB classification.
	Method	Log Rank
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Azacitidine, Conventional Care
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.0027
	Comments
	Method	Regression, Cox
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.68
	Confidence Interval	(2-Sided) 95% 0.53 to 0.87
	Parameter Dispersion	Type: Value:
	Estimation Comments	Cox proportional hazards model stratified on the randomization factors of FAB and IPSS with model term of treatment.

4. Secondary Outcome

Title	Kaplan-Meier Estimates for Median Time to Transformation to Acute Myeloid Leukemia (AML)
Description	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

Outcome Measure Data

Analysis Population Description
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/Group Title	Azacitidine	Conventional Care
Arm/Group Description	Azacitidine, 75 mg/m^2/day given by subcutaneous injection for 7 days of every 28 day cycle, plus best supportive care.	Physician choice of low dose cytarabine, standard chemotherapy, or best supportive care (consisting of blood products, growth factors, antibiotics)
Measure Participants	179	179
Median (95% Confidence Interval) [months]	20.66	15.44

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Azacitidine, Conventional Care
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.2555
	Comments	The p value is two-sided from the log rank test stratified by the randomization stratification factors of IPSS classification and FAB classification
	Method	Log Rank
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Azacitidine, Conventional Care
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.2562
	Comments
	Method	Regression, Cox
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.83
	Confidence Interval	(2-Sided) 95% 0.60 to 1.15
	Parameter Dispersion	Type: Value:
	Estimation Comments	Cox proportional hazards model stratified on the randomization factors of FAB and IPSS with model term of treatment.

5. Secondary Outcome

Title	Summary of Participants' Red Blood Cell (RBC) Transfusion Status for Participants Who Were Transfusion Dependent at Baseline
Description	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

Outcome Measure Data

Analysis Population Description
Intent to treat population

Arm/Group Title	Azacitidine	Conventional Care
Arm/Group Description	Azacitidine, 75 mg/m^2/day given by subcutaneous injection for 7 days of every 28 day cycle, plus best supportive care.	Physician choice of low dose cytarabine, standard chemotherapy, or best supportive care (consisting of blood products, growth factors, antibiotics)
Measure Participants	111	114
Baseline Dependent; On-Treatment Independent	50 27.9%	13 7.3%
Baseline Dependent; On-Treatment Dependent	61 34.1%	101 56.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Azacitidine, Conventional Care
	Comments	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.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Fisher Exact
	Comments

6. Secondary Outcome

Title	Summary of Participants' Red Blood Cell (RBC) Transfusion Status for Participants Who Were Transfusion Independent at Baseline
Description	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

Outcome Measure Data

Analysis Population Description
Intent to treat population

Arm/Group Title	Azacitidine	Conventional Care
Arm/Group Description	Azacitidine, 75 mg/m^2/day given by subcutaneous injection for 7 days of every 28 day cycle, plus best supportive care.	Physician choice of low dose cytarabine, standard chemotherapy, or best supportive care (consisting of blood products, growth factors, antibiotics)
Measure Participants	68	65
Baseline Independent; On-Treatment Independent	58 32.4%	37 20.7%
Baseline Independent; On-Treatment Dependent	10 5.6%	28 15.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Azacitidine, Conventional Care
	Comments	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.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.0005
	Comments
	Method	Fisher Exact
	Comments

7. Secondary Outcome

Title	Summary of Participants' Platelet Transfusion Status for Participants Who Were Transfusion Dependent at Baseline
Description	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

Outcome Measure Data

Analysis Population Description
Intent to treat population

Arm/Group Title	Azacitidine	Conventional Care
Arm/Group Description	Azacitidine, 75 mg/m^2/day given by subcutaneous injection for 7 days of every 28 day cycle, plus best supportive care.	Physician choice of low dose cytarabine, standard chemotherapy, or best supportive care (consisting of blood products, growth factors, antibiotics)
Measure Participants	38	27
Baseline Dependent; On-Treatment Independent	16 8.9%	11 6.1%
Baseline Dependent; On-Treatment Dependent	22 12.3%	16 8.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Azacitidine, Conventional Care
	Comments	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
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	1.000
	Comments
	Method	Fisher Exact
	Comments

8. Secondary Outcome

Title	Summary of Participants' Platelet Transfusion Status for Participants Who Were Transfusion Independent at Baseline
Description	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

Outcome Measure Data

Analysis Population Description
Intent to treat population

Arm/Group Title	Azacitidine	Conventional Care
Arm/Group Description	Azacitidine, 75 mg/m^2/day given by subcutaneous injection for 7 days of every 28 day cycle, plus best supportive care.	Physician choice of low dose cytarabine, standard chemotherapy, or best supportive care (consisting of blood products, growth factors, antibiotics)
Measure Participants	141	152
Baseline Independent; On-Treatment Independent	126 70.4%	102 57%
Baseline Independent; On-Treatment Dependent	15 8.4%	50 27.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Azacitidine, Conventional Care
	Comments	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.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Fisher Exact
	Comments

9. Secondary Outcome

Title	Number of Participants Considered Hematologic Responders by Investigator Determinations Using International Working Group (IWG 2000) Criteria for Myelodysplastic Syndrome (MDS)
Description	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

Outcome Measure Data

Analysis Population Description
Intent to treat population.

Arm/Group Title	Azacitidine	Conventional Care
Arm/Group Description	Azacitidine, 75 mg/m^2/day given by subcutaneous injection for 7 days of every 28 day cycle, plus best supportive care.	Physician choice of low dose cytarabine, standard chemotherapy, or best supportive care (consisting of blood products, growth factors, antibiotics)
Measure Participants	179	179
Overall (Complete + Partial Remission)	51 28.5%	21 11.7%
Complete Remission	30 16.8%	14 7.8%
Partial Remission	21 11.7%	7 3.9%
Stable Disease	75 41.9%	65 36.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Azacitidine, Conventional Care
	Comments	Overall (Complete + Partial Remission)
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.0001
	Comments
	Method	Fisher Exact
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Azacitidine, Conventional Care
	Comments	Complete remission
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.0150
	Comments
	Method	Fisher Exact
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Azacitidine, Conventional Care
	Comments	Partial Remission
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.0094
	Comments
	Method	Fisher Exact
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Azacitidine, Conventional Care
	Comments	Stable Disease
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.3297
	Comments
	Method	Fisher Exact
	Comments

10. Secondary Outcome

Title	Number of Participants Showing Hematologic Improvement Using International Working Group (IWG 2000) Criteria for Myelodysplastic Syndrome (MDS) Assessed by Independent Review Committee
Description	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

Outcome Measure Data

Analysis Population Description
Intent to treat population.

Arm/Group Title	Azacitidine	Conventional Care
Arm/Group Description	Azacitidine, 75 mg/m^2/day given by subcutaneous injection for 7 days of every 28 day cycle, plus best supportive care.	Physician choice of low dose cytarabine, standard chemotherapy, or best supportive care (consisting of blood products, growth factors, antibiotics)
Measure Participants	179	179
Any Improvement n=177, 178	87 48.6%	51 28.5%
Erythroid Response - Major n=157, 160	62 34.6%	17 9.5%
Erythroid Response - Minor n=157, 160	2 1.1%	1 0.6%
Platelet Response - Major n=141, 129	46 25.7%	18 10.1%
Platelet Response - Minor n=138, 127	6 3.4%	4 2.2%
Neutrophil Response - Major n=131, 111	25 14%	20 11.2%
Neutrophil Response - Minor n=131, 111	5 2.8%	9 5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Azacitidine, Conventional Care
	Comments	Any Improvement
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Fisher Exact
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Azacitidine, Conventional Care
	Comments	Erythroid Response - Major
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Fisher Exact
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Azacitidine, Conventional Care
	Comments	Erythroid Response - Minor
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.6203
	Comments
	Method	Fisher Exact
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Azacitidine, Conventional Care
	Comments	Platelet Response - Major
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.0003
	Comments
	Method	Fisher Exact
	Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Azacitidine, Conventional Care
	Comments	Platelet Response - Minor
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.7514
	Comments
	Method	Fisher Exact
	Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Azacitidine, Conventional Care
	Comments	Neutrophil Response - Major
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.8695
	Comments
	Method	Fisher Exact
	Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Azacitidine, Conventional Care
	Comments	Neutrophil Response - Minor
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.1760
	Comments
	Method	Fisher Exact
	Comments

11. Secondary Outcome

Title	Time to Disease Progression, Relapse After Complete or Partial Remission, or Death From Any Cause
Description	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

Outcome Measure Data

Analysis Population Description
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/Group Title	Azacitidine	Conventional Care
Arm/Group Description	Azacitidine, 75 mg/m^2/day given by subcutaneous injection for 7 days of every 28 day cycle, plus best supportive care.	Physician choice of low dose cytarabine, standard chemotherapy, or best supportive care (consisting of blood products, growth factors, antibiotics)
Measure Participants	179	179
Median (95% Confidence Interval) [months]	14.13	8.82

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Azacitidine, Conventional Care
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.0466
	Comments	The p value is two-sided from the log rank test which compares whether the azacitidine and control group follow the same duration curve.
	Method	Log Rank
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Azacitidine, Conventional Care
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.0474
	Comments
	Method	Regression, Cox
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.73
	Confidence Interval	(2-Sided) 95% 0.53 to 1.00
	Parameter Dispersion	Type: Value:
	Estimation Comments

12. Secondary Outcome

Title	Duration of Any Hematologic Improvement
Description	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

Outcome Measure Data

Analysis Population Description
Intent to treat population. Participants showing hematologic improvement were 48 in azacitidine and 31 in conventional care.

Arm/Group Title	Azacitidine	Conventional Care
Arm/Group Description	Azacitidine, 75 mg/m^2/day given by subcutaneous injection for 7 days of every 28 day cycle, plus best supportive care.	Physician choice of low dose cytarabine, standard chemotherapy, or best supportive care (consisting of blood products, growth factors, antibiotics)
Measure Participants	87	51
Median (95% Confidence Interval) [months]	13.57	5.18

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Azacitidine, Conventional Care
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.0002
	Comments	The p value is two-sided from the log rank test which compares whether the azacitidine and control group follow the same duration curve.
	Method	Log Rank
	Comments

13. Secondary Outcome

Title	Number of Infections Per Treatment Year Requiring Intravenous Antibiotics, Antifungals or Antivirals
Description	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

Outcome Measure Data

Analysis Population Description
Intent to treat population

Arm/Group Title	Azacitidine	Conventional Care
Arm/Group Description	Azacitidine, 75 mg/m^2/day given by subcutaneous injection for 7 days of every 28 day cycle, plus best supportive care.	Physician choice of low dose cytarabine, standard chemotherapy, or best supportive care (consisting of blood products, growth factors, antibiotics)
Measure Participants	179	179
Number [infections per treatment year]	0.16	0.24

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Azacitidine, Conventional Care
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.1327
	Comments
	Method	exact binomial
	Comments

Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	0.67
	Confidence Interval	(2-Sided) 95% 0.35 to 1.20
	Parameter Dispersion	Type: Value:
	Estimation Comments

14. Secondary Outcome

Title	Number of Participants in Different Categories of Adverse Experiences During Core Study Period
Description	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

Outcome Measure Data

Analysis Population Description
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/Group Title	Azacitidine	Best Supportive Care Only	Low-dose Cytarabine	Standard Chemotherapy
Arm/Group Description	Azacitidine, 75 mg/m2/day given by subcutaneous injection for 7 days of every 28 day cycle, plus best supportive care.	Care can include transfusions, antibiotics, myeloid growth factors [G-CSF and GM CSF] for neutropenic infections until the end of the study.	Cytarabine, 20 mg/m2/day subcutaneously on Days 1-14, with 28-42 days between cycles. Plus best supportive care.	Induction cycle: Cytarabine infusion 100-200 mg/m2/day on days 1-7 + anthracycline on days 1, 2, 3 Consolidation cycle: Cytarabine infusion 100-200 mg/m2/day for 3-7 days + anthracycline on days 1 and 2 There are 28-70 days between cycles - 1 induction cycle and maximum of 2 consolidation cycles; best supportive care follows the final consolidation cycle.
Measure Participants	175	102	44	19
Patients with >=1 treatment emergent AE (TEAE)	175 97.8%	97 54.2%	44 12.3%	19 NaN
Patients with >=1 treatment related TEAE	169 94.4%	1 0.6%	34 9.5%	19 NaN
Patients with >=1 serious TEAE	114 63.7%	71 39.7%	27 7.5%	14 NaN
Patients with >=1 serious treatment related TEAE	43 24%	0 0%	13 3.6%	13 NaN
Patients w TEAE leading to discontinued treatment	22 12.3%	4 2.2%	6 1.7%	2 NaN
Patients w TEAE leading to dose reduction	20 11.2%	0 0%	2 0.6%	0 NaN
Patients w TEAE leading to dose interruption	82 45.8%	0 0%	12 3.4%	0 NaN

15. Post-Hoc Outcome

Title	Kaplan-Meier Estimates for Median Time to Transformation to Acute Myeloid Leukemia (AML) Based on the Last Bone Marrow Assessment
Description	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

Outcome Measure Data

Analysis Population Description
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/Group Title	Azacitidine	Conventional Care
Arm/Group Description	Azacitidine, 75 mg/m^2/day given by subcutaneous injection for 7 days of every 28 day cycle, plus best supportive care.	Physician choice of low dose cytarabine, standard chemotherapy, or best supportive care (consisting of blood products, growth factors, antibiotics)
Measure Participants	179	179
Median (95% Confidence Interval) [months]	17.80	11.48

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Azacitidine, Conventional Care
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	The p value is two-sided from the log rank test stratified by the randomization stratification factors of IPSS classification and FAB classification
	Method	Log Rank
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Azacitidine, Conventional Care
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Regression, Cox
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.50
	Confidence Interval	(2-Sided) 95% 0.35 to 0.70
	Parameter Dispersion	Type: Value:
	Estimation Comments	Cox proportional hazards model stratified on the randomization factors of FAB and IPSS with model term of treatment.

16. Primary Outcome

Title	Number of Participants Who Died
Description	Count of participants who died during the study
Time Frame	42 months

Outcome Measure Data

Analysis Population Description
Intent to treat population

Arm/Group Title	Azacitidine	Conventional Care
Arm/Group Description	Azacitidine, 75 mg/m^2/day given by subcutaneous injection for 7 days of every 28 day cycle, plus best supportive care.	Physician choice of low dose cytarabine, standard chemotherapy, or best supportive care (consisting of blood products, growth factors, antibiotics)
Measure Participants	179	179
Number [participants]	82 45.8%	113 63.1%

Adverse Events

	Azacitidine		Best Supportive Care Only		Low-dose Cytarabine		Standard Chemotherapy
Time Frame	Treatment-emergent AEs for the 'core study' from Day 1 to 42 months.
Adverse Event Reporting Description	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/Group Title	Azacitidine		Best Supportive Care Only		Low-dose Cytarabine		Standard Chemotherapy
Arm/Group Description	Azacitidine, 75 mg/m2/day given by subcutaneous injection for 7 days of every 28 day cycle, plus best supportive care.		Care can include transfusions, antibiotics, myeloid growth factors [G-CSF and GM CSF] for neutropenic infections until the end of the study.		Cytarabine, 20 mg/m2/day subcutaneously on Days 1-14, with 28-42 days between cycles. Plus best supportive care.		Induction cycle: Cytarabine infusion 100-200 mg/m2/day on days 1-7 + anthracycline on days 1, 2, 3 Consolidation cycle: Cytarabine infusion 100-200 mg/m2/day for 3-7 days + anthracycline on days 1 and 2 There are 28-70 days between cycles - 1 induction cycle and maximum of 2 consolidation cycles; best supportive care follows the final consolidation cycle.
All Cause Mortality
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Azacitidine		Best Supportive Care Only		Low-dose Cytarabine		Standard Chemotherapy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	114/175 (65.1%)		71/102 (69.6%)		27/44 (61.4%)		14/19 (73.7%)
Blood and lymphatic system disorders
Anaemia	12/175 (6.9%)		3/102 (2.9%)		2/44 (4.5%)		0/19 (0%)
Bone marrow failure	2/175 (1.1%)		0/102 (0%)		0/44 (0%)		1/19 (5.3%)
Febrile bone marrow aplasia	0/175 (0%)		0/102 (0%)		2/44 (4.5%)		0/19 (0%)
Febrile neutropenia	19/175 (10.9%)		3/102 (2.9%)		1/44 (2.3%)		5/19 (26.3%)
Haemolysis	0/175 (0%)		1/102 (1%)		0/44 (0%)		0/19 (0%)
Haemorrhagic diathesis	0/175 (0%)		0/102 (0%)		0/44 (0%)		1/19 (5.3%)
Leukocytosis	0/175 (0%)		0/102 (0%)		1/44 (2.3%)		0/19 (0%)
Leukopenia	1/175 (0.6%)		0/102 (0%)		0/44 (0%)		0/19 (0%)
Neutropenia	5/175 (2.9%)		0/102 (0%)		0/44 (0%)		1/19 (5.3%)
Pancytopenia	2/175 (1.1%)		0/102 (0%)		0/44 (0%)		0/19 (0%)
Thrombocytopenia	8/175 (4.6%)		2/102 (2%)		2/44 (4.5%)		1/19 (5.3%)
Cardiac disorders
Acute myocardial infarction	0/175 (0%)		1/102 (1%)		0/44 (0%)		0/19 (0%)
Angina pectoris	2/175 (1.1%)		1/102 (1%)		0/44 (0%)		0/19 (0%)
Atrial fibrillation	1/175 (0.6%)		1/102 (1%)		0/44 (0%)		1/19 (5.3%)
Cardiac failure	3/175 (1.7%)		2/102 (2%)		1/44 (2.3%)		0/19 (0%)
Cardiac failure acute	2/175 (1.1%)		1/102 (1%)		0/44 (0%)		0/19 (0%)
Cardiac failure congestive	0/175 (0%)		2/102 (2%)		0/44 (0%)		0/19 (0%)
Cardiomyopathy	0/175 (0%)		1/102 (1%)		0/44 (0%)		0/19 (0%)
Coronary artery disease	0/175 (0%)		0/102 (0%)		0/44 (0%)		1/19 (5.3%)
Coronary artery occlusion	0/175 (0%)		1/102 (1%)		0/44 (0%)		0/19 (0%)
Left ventricular failure	0/175 (0%)		1/102 (1%)		0/44 (0%)		0/19 (0%)
Myocardial infarction	2/175 (1.1%)		0/102 (0%)		0/44 (0%)		1/19 (5.3%)
Pericardial effusion	1/175 (0.6%)		0/102 (0%)		0/44 (0%)		0/19 (0%)
Ventricular tachycardia	1/175 (0.6%)		0/102 (0%)		0/44 (0%)		0/19 (0%)
Ear and labyrinth disorders
Vertigo	1/175 (0.6%)		2/102 (2%)		0/44 (0%)		0/19 (0%)
Vestibular disorder	0/175 (0%)		1/102 (1%)		0/44 (0%)		0/19 (0%)
Endocrine disorders
Hypothyroidism	1/175 (0.6%)		0/102 (0%)		0/44 (0%)		0/19 (0%)
Eye disorders
Angle closure glaucoma	1/175 (0.6%)		0/102 (0%)		0/44 (0%)		0/19 (0%)
Endophthalmitis	1/175 (0.6%)		0/102 (0%)		0/44 (0%)		0/19 (0%)
Eye Haemorrhage	2/175 (1.1%)		0/102 (0%)		0/44 (0%)		0/19 (0%)
Myopia	1/175 (0.6%)		0/102 (0%)		0/44 (0%)		0/19 (0%)
Retinal artery occlusion	1/175 (0.6%)		0/102 (0%)		0/44 (0%)		0/19 (0%)
Retinal Haemorrhage	1/175 (0.6%)		0/102 (0%)		0/44 (0%)		0/19 (0%)
Retinal tear	1/175 (0.6%)		0/102 (0%)		0/44 (0%)		0/19 (0%)
Strabismus	1/175 (0.6%)		0/102 (0%)		0/44 (0%)		0/19 (0%)
Gastrointestinal disorders
Abdominal pain	2/175 (1.1%)		0/102 (0%)		0/44 (0%)		0/19 (0%)
Anal fissure	0/175 (0%)		1/102 (1%)		0/44 (0%)		0/19 (0%)
Anal fistula	0/175 (0%)		0/102 (0%)		1/44 (2.3%)		0/19 (0%)
Caecitis	0/175 (0%)		0/102 (0%)		1/44 (2.3%)		0/19 (0%)
Colitis ulcerative	1/175 (0.6%)		0/102 (0%)		0/44 (0%)		0/19 (0%)
Constipation	1/175 (0.6%)		0/102 (0%)		0/44 (0%)		0/19 (0%)
Diarrhoea	0/175 (0%)		1/102 (1%)		0/44 (0%)		0/19 (0%)
Dysphagia	0/175 (0%)		0/102 (0%)		0/44 (0%)		1/19 (5.3%)
Food poisoning	1/175 (0.6%)		0/102 (0%)		0/44 (0%)		0/19 (0%)
Gastritis	0/175 (0%)		1/102 (1%)		0/44 (0%)		0/19 (0%)
Gastritis haemorrhagic	0/175 (0%)		1/102 (1%)		0/44 (0%)		0/19 (0%)
Gastrointestinal haemorrhage	1/175 (0.6%)		1/102 (1%)		0/44 (0%)		0/19 (0%)
Gingival bleeding	2/175 (1.1%)		0/102 (0%)		0/44 (0%)		0/19 (0%)
Haematemesis	1/175 (0.6%)		0/102 (0%)		0/44 (0%)		0/19 (0%)
Haemorrhoidal haemorrhage	1/175 (0.6%)		0/102 (0%)		0/44 (0%)		0/19 (0%)
Ileitis	0/175 (0%)		0/102 (0%)		1/44 (2.3%)		0/19 (0%)
Intestinal haemorrhage	1/175 (0.6%)		0/102 (0%)		0/44 (0%)		0/19 (0%)
Large intestinal haemorrhage	0/175 (0%)		1/102 (1%)		0/44 (0%)		0/19 (0%)
Melaena	0/175 (0%)		2/102 (2%)		0/44 (0%)		0/19 (0%)
Mouth haemorrhage	1/175 (0.6%)		0/102 (0%)		0/44 (0%)		0/19 (0%)
Neutropenic colitis	0/175 (0%)		0/102 (0%)		0/44 (0%)		2/19 (10.5%)
Rectal haemorrhage	2/175 (1.1%)		0/102 (0%)		0/44 (0%)		0/19 (0%)
Stomatitis	1/175 (0.6%)		0/102 (0%)		0/44 (0%)		0/19 (0%)
Subileus	1/175 (0.6%)		0/102 (0%)		0/44 (0%)		0/19 (0%)
Tooth disorder	1/175 (0.6%)		0/102 (0%)		0/44 (0%)		0/19 (0%)
General disorders
Asthenia	1/175 (0.6%)		0/102 (0%)		1/44 (2.3%)		0/19 (0%)
Catheter site inflammation	0/175 (0%)		0/102 (0%)		1/44 (2.3%)		0/19 (0%)
Chest pain	1/175 (0.6%)		0/102 (0%)		0/44 (0%)		0/19 (0%)
Death	0/175 (0%)		2/102 (2%)		0/44 (0%)		0/19 (0%)
Facial pain	0/175 (0%)		1/102 (1%)		0/44 (0%)		0/19 (0%)
Fatigue	0/175 (0%)		1/102 (1%)		0/44 (0%)		0/19 (0%)
General physical health deterioration	2/175 (1.1%)		0/102 (0%)		0/44 (0%)		0/19 (0%)
Injection site nodule	1/175 (0.6%)		0/102 (0%)		0/44 (0%)		0/19 (0%)
Injection site pain	1/175 (0.6%)		0/102 (0%)		0/44 (0%)		0/19 (0%)
Mucosal inflammation	0/175 (0%)		0/102 (0%)		1/44 (2.3%)		1/19 (5.3%)
Pain	0/175 (0%)		0/102 (0%)		1/44 (2.3%)		0/19 (0%)
Pyrexia	10/175 (5.7%)		3/102 (2.9%)		5/44 (11.4%)		0/19 (0%)
Hepatobiliary disorders
Bile duct stone	1/175 (0.6%)		0/102 (0%)		0/44 (0%)		0/19 (0%)
Hepatic function abnormal	1/175 (0.6%)		0/102 (0%)		0/44 (0%)		0/19 (0%)
Immune system disorders
Drug hypersensitivity	0/175 (0%)		1/102 (1%)		0/44 (0%)		0/19 (0%)
Infections and infestations
Abdominal wall abscess	1/175 (0.6%)		0/102 (0%)		0/44 (0%)		0/19 (0%)
Abscess neck	1/175 (0.6%)		0/102 (0%)		0/44 (0%)		0/19 (0%)
Arthritis infection	0/175 (0%)		0/102 (0%)		1/44 (2.3%)		0/19 (0%)
Aspergillosis	0/175 (0%)		0/102 (0%)		0/44 (0%)		1/19 (5.3%)
Bacteraemia	2/175 (1.1%)		0/102 (0%)		0/44 (0%)		2/19 (10.5%)
Bronchitis	1/175 (0.6%)		0/102 (0%)		1/44 (2.3%)		0/19 (0%)
Bronchopneumonia	3/175 (1.7%)		3/102 (2.9%)		0/44 (0%)		0/19 (0%)
Candidiasis	0/175 (0%)		0/102 (0%)		1/44 (2.3%)		0/19 (0%)
Cellulitis	2/175 (1.1%)		2/102 (2%)		2/44 (4.5%)		0/19 (0%)
Clostridium difficile colitis	1/175 (0.6%)		0/102 (0%)		0/44 (0%)		0/19 (0%)
Corynebacterium infection	1/175 (0.6%)		0/102 (0%)		0/44 (0%)		0/19 (0%)
Disseminated tuberculosis	0/175 (0%)		0/102 (0%)		1/44 (2.3%)		0/19 (0%)
Diverticulitis	0/175 (0%)		0/102 (0%)		0/44 (0%)		1/19 (5.3%)
Ear infection	1/175 (0.6%)		0/102 (0%)		0/44 (0%)		0/19 (0%)
Enterobacter bacteraemia	1/175 (0.6%)		0/102 (0%)		0/44 (0%)		0/19 (0%)
Escherichia sepsis	0/175 (0%)		2/102 (2%)		0/44 (0%)		0/19 (0%)
Escherichia urinary tract infection	0/175 (0%)		1/102 (1%)		0/44 (0%)		0/19 (0%)
Fungal sepsis	1/175 (0.6%)		0/102 (0%)		1/44 (2.3%)		0/19 (0%)
Gasteroenteritis	1/175 (0.6%)		1/102 (1%)		0/44 (0%)		0/19 (0%)
Gasteroenteritis salmonella	1/175 (0.6%)		0/102 (0%)		0/44 (0%)		0/19 (0%)
Gingival infection	0/175 (0%)		1/102 (1%)		0/44 (0%)		0/19 (0%)
Herpes zoster	1/175 (0.6%)		0/102 (0%)		0/44 (0%)		0/19 (0%)
Infection	0/175 (0%)		1/102 (1%)		0/44 (0%)		1/19 (5.3%)
Klebsiella bacteraemia	0/175 (0%)		0/102 (0%)		0/44 (0%)		1/19 (5.3%)
Laryngopharyngitis	1/175 (0.6%)		0/102 (0%)		0/44 (0%)		0/19 (0%)
Lobar pneumonia	1/175 (0.6%)		0/102 (0%)		0/44 (0%)		0/19 (0%)
Lower respiratory tract infection	2/175 (1.1%)		0/102 (0%)		0/44 (0%)		0/19 (0%)
Lung infection	2/175 (1.1%)		0/102 (0%)		0/44 (0%)		0/19 (0%)
Meningitis	1/175 (0.6%)		0/102 (0%)		0/44 (0%)		0/19 (0%)
Mucormycosis	1/175 (0.6%)		0/102 (0%)		0/44 (0%)		0/19 (0%)
Neutropenic infection	1/175 (0.6%)		0/102 (0%)		0/44 (0%)		0/19 (0%)
Neutropenic sepsis	4/175 (2.3%)		1/102 (1%)		1/44 (2.3%)		2/19 (10.5%)
Oral herpes	1/175 (0.6%)		0/102 (0%)		1/44 (2.3%)		0/19 (0%)
Parotitis	1/175 (0.6%)		0/102 (0%)		0/44 (0%)		0/19 (0%)
Perianal abscess	2/175 (1.1%)		0/102 (0%)		0/44 (0%)		0/19 (0%)
Pneumonia	20/175 (11.4%)		12/102 (11.8%)		2/44 (4.5%)		3/19 (15.8%)
Pneumonia bacterial	0/175 (0%)		1/102 (1%)		0/44 (0%)		0/19 (0%)
Pneumonia fungal	1/175 (0.6%)		0/102 (0%)		0/44 (0%)		2/19 (10.5%)
Pseudomembranous colitis	0/175 (0%)		1/102 (1%)		0/44 (0%)		0/19 (0%)
Pseudomonal sepsis	0/175 (0%)		1/102 (1%)		0/44 (0%)		0/19 (0%)
Pulmonary tuberculosis	1/175 (0.6%)		0/102 (0%)		0/44 (0%)		0/19 (0%)
Renal abscess	0/175 (0%)		1/102 (1%)		0/44 (0%)		0/19 (0%)
Respiratory tract infection	1/175 (0.6%)		1/102 (1%)		0/44 (0%)		0/19 (0%)
Salmonella sepsis	1/175 (0.6%)		0/102 (0%)		0/44 (0%)		0/19 (0%)
Sepsis	6/175 (3.4%)		3/102 (2.9%)		2/44 (4.5%)		0/19 (0%)
Septic shock	3/175 (1.7%)		1/102 (1%)		2/44 (4.5%)		0/19 (0%)
Sialoadenitis	1/175 (0.6%)		0/102 (0%)		0/44 (0%)		0/19 (0%)
Splenic abscess	1/175 (0.6%)		0/102 (0%)		0/44 (0%)		0/19 (0%)
Staphylococcal bacteraemia	1/175 (0.6%)		0/102 (0%)		0/44 (0%)		0/19 (0%)
Subcutaneous abscess	1/175 (0.6%)		0/102 (0%)		0/44 (0%)		0/19 (0%)
Subdiaphragmatic abscess	1/175 (0.6%)		0/102 (0%)		0/44 (0%)		0/19 (0%)
Tooth abscess	1/175 (0.6%)		0/102 (0%)		0/44 (0%)		0/19 (0%)
Tuberculosis	0/175 (0%)		1/102 (1%)		0/44 (0%)		0/19 (0%)
Upper respiratory tract infection	2/175 (1.1%)		0/102 (0%)		0/44 (0%)		0/19 (0%)
Urinary tract infection	5/175 (2.9%)		0/102 (0%)		2/44 (4.5%)		1/19 (5.3%)
Bronchopulmonary aspergillosis	2/175 (1.1%)		0/102 (0%)		0/44 (0%)		0/19 (0%)
Injury, poisoning and procedural complications
Clavicle fracture	1/175 (0.6%)		0/102 (0%)		0/44 (0%)		0/19 (0%)
Hip fracture	1/175 (0.6%)		0/102 (0%)		0/44 (0%)		0/19 (0%)
Subdural haematoma	0/175 (0%)		0/102 (0%)		1/44 (2.3%)		0/19 (0%)
Synovial rupture	1/175 (0.6%)		0/102 (0%)		0/44 (0%)		0/19 (0%)
Transfusion reaction	3/175 (1.7%)		0/102 (0%)		1/44 (2.3%)		0/19 (0%)
Traumatic intracranial haemorrhage	1/175 (0.6%)		0/102 (0%)		0/44 (0%)		0/19 (0%)
Upper limb fracture	0/175 (0%)		1/102 (1%)		0/44 (0%)		0/19 (0%)
Metabolism and nutrition disorders
Diabetes mellitus	1/175 (0.6%)		0/102 (0%)		0/44 (0%)		0/19 (0%)
Haemosiderosis	0/175 (0%)		1/102 (1%)		0/44 (0%)		0/19 (0%)
Hyperkalaemia	0/175 (0%)		1/102 (1%)		0/44 (0%)		0/19 (0%)
Hypokalaemia	0/175 (0%)		1/102 (1%)		0/44 (0%)		0/19 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	0/175 (0%)		1/102 (1%)		0/44 (0%)		0/19 (0%)
Arthritis	0/175 (0%)		1/102 (1%)		0/44 (0%)		0/19 (0%)
Back pain	0/175 (0%)		1/102 (1%)		0/44 (0%)		0/19 (0%)
Bursitis	0/175 (0%)		1/102 (1%)		0/44 (0%)		0/19 (0%)
Chondrocalcinosis pyrophosphate	0/175 (0%)		0/102 (0%)		0/44 (0%)		1/19 (5.3%)
Osteoporosis	1/175 (0.6%)		0/102 (0%)		0/44 (0%)		0/19 (0%)
Pain in extremity	0/175 (0%)		1/102 (1%)		0/44 (0%)		0/19 (0%)
Pathological fracture	0/175 (0%)		1/102 (1%)		0/44 (0%)		0/19 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Acute myeloid leukaemia	30/175 (17.1%)		35/102 (34.3%)		6/44 (13.6%)		1/19 (5.3%)
Colon cancer	1/175 (0.6%)		0/102 (0%)		0/44 (0%)		0/19 (0%)
Lung adenocarcinoma	1/175 (0.6%)		0/102 (0%)		0/44 (0%)		0/19 (0%)
Myelodysplastic syndrome	4/175 (2.3%)		2/102 (2%)		1/44 (2.3%)		0/19 (0%)
Myelofibrosis	1/175 (0.6%)		0/102 (0%)		0/44 (0%)		0/19 (0%)
Neoplasm prostate	1/175 (0.6%)		0/102 (0%)		0/44 (0%)		0/19 (0%)
Oesophageal carcinoma	1/175 (0.6%)		0/102 (0%)		0/44 (0%)		0/19 (0%)
Squamous cell carcinoma of skin	1/175 (0.6%)		0/102 (0%)		0/44 (0%)		0/19 (0%)
Urinary tract neoplasm	1/175 (0.6%)		0/102 (0%)		0/44 (0%)		0/19 (0%)
Nervous system disorders
Cerebral haemorrhage	4/175 (2.3%)		3/102 (2.9%)		0/44 (0%)		0/19 (0%)
Cerebral ischaemia	0/175 (0%)		0/102 (0%)		1/44 (2.3%)		0/19 (0%)
Coma	1/175 (0.6%)		0/102 (0%)		0/44 (0%)		0/19 (0%)
Convulsion	0/175 (0%)		1/102 (1%)		0/44 (0%)		0/19 (0%)
Dizziness	0/175 (0%)		0/102 (0%)		0/44 (0%)		1/19 (5.3%)
Grand mal convulsion	0/175 (0%)		1/102 (1%)		0/44 (0%)		0/19 (0%)
Haemorrhage intracranial	1/175 (0.6%)		1/102 (1%)		0/44 (0%)		0/19 (0%)
Headache	0/175 (0%)		1/102 (1%)		0/44 (0%)		0/19 (0%)
Intracranial haematoma	0/175 (0%)		1/102 (1%)		0/44 (0%)		0/19 (0%)
Loss of consciousness	1/175 (0.6%)		0/102 (0%)		0/44 (0%)		0/19 (0%)
Somnolence	0/175 (0%)		0/102 (0%)		1/44 (2.3%)		0/19 (0%)
Syncope	2/175 (1.1%)		0/102 (0%)		0/44 (0%)		0/19 (0%)
Transient ischaemic attack	1/175 (0.6%)		0/102 (0%)		0/44 (0%)		0/19 (0%)
Psychiatric disorders
Confusional state	1/175 (0.6%)		0/102 (0%)		0/44 (0%)		0/19 (0%)
Delirium	1/175 (0.6%)		0/102 (0%)		0/44 (0%)		0/19 (0%)
Depression	1/175 (0.6%)		0/102 (0%)		0/44 (0%)		0/19 (0%)
Psychotic disorder	1/175 (0.6%)		0/102 (0%)		0/44 (0%)		0/19 (0%)
Renal and urinary disorders
Haematuria	2/175 (1.1%)		1/102 (1%)		0/44 (0%)		0/19 (0%)
Nephrolithiasis	0/175 (0%)		1/102 (1%)		0/44 (0%)		0/19 (0%)
Renal colic	1/175 (0.6%)		0/102 (0%)		0/44 (0%)		0/19 (0%)
Renal failure	1/175 (0.6%)		1/102 (1%)		0/44 (0%)		0/19 (0%)
Renal failure acute	0/175 (0%)		2/102 (2%)		0/44 (0%)		0/19 (0%)
Renal impairment	0/175 (0%)		1/102 (1%)		0/44 (0%)		0/19 (0%)
Urethral stenosis	1/175 (0.6%)		0/102 (0%)		0/44 (0%)		0/19 (0%)
Urinary retention	1/175 (0.6%)		0/102 (0%)		0/44 (0%)		0/19 (0%)
Reproductive system and breast disorders
Benign prostatic hyperplasia	1/175 (0.6%)		0/102 (0%)		0/44 (0%)		0/19 (0%)
Metrorrhagia	0/175 (0%)		1/102 (1%)		0/44 (0%)		0/19 (0%)
Prostatitis	0/175 (0%)		1/102 (1%)		0/44 (0%)		0/19 (0%)
Vaginal haemorrhage	0/175 (0%)		1/102 (1%)		0/44 (0%)		0/19 (0%)
Respiratory, thoracic and mediastinal disorders
Acute pulmonary oedema	1/175 (0.6%)		0/102 (0%)		0/44 (0%)		0/19 (0%)
Acute respiratory failure	1/175 (0.6%)		0/102 (0%)		0/44 (0%)		0/19 (0%)
Bronchitis chronic	0/175 (0%)		1/102 (1%)		0/44 (0%)		0/19 (0%)
Chronic obstructive pulmonary disease	0/175 (0%)		1/102 (1%)		0/44 (0%)		0/19 (0%)
Epistaxis	4/175 (2.3%)		3/102 (2.9%)		2/44 (4.5%)		0/19 (0%)
Haemoptysis	1/175 (0.6%)		0/102 (0%)		1/44 (2.3%)		0/19 (0%)
Lung infiltration	1/175 (0.6%)		0/102 (0%)		0/44 (0%)		0/19 (0%)
Pleural effusion	2/175 (1.1%)		1/102 (1%)		0/44 (0%)		0/19 (0%)
Pleuritic pain	0/175 (0%)		1/102 (1%)		0/44 (0%)		0/19 (0%)
Pneumonitis	1/175 (0.6%)		0/102 (0%)		0/44 (0%)		0/19 (0%)
Pulmonary embolism	1/175 (0.6%)		0/102 (0%)		0/44 (0%)		1/19 (5.3%)
Pulmonary fibrosis	1/175 (0.6%)		0/102 (0%)		0/44 (0%)		0/19 (0%)
Pulmonary hypertension	0/175 (0%)		1/102 (1%)		0/44 (0%)		0/19 (0%)
Respiratory failure	1/175 (0.6%)		1/102 (1%)		0/44 (0%)		0/19 (0%)
Skin and subcutaneous tissue disorders
Actinic keratosis	1/175 (0.6%)		0/102 (0%)		0/44 (0%)		0/19 (0%)
Pruritus	1/175 (0.6%)		0/102 (0%)		0/44 (0%)		0/19 (0%)
Purpura	0/175 (0%)		0/102 (0%)		1/44 (2.3%)		0/19 (0%)
Vascular disorders
Aortic aneurysm	1/175 (0.6%)		0/102 (0%)		0/44 (0%)		0/19 (0%)
Circulatory collapse	1/175 (0.6%)		0/102 (0%)		0/44 (0%)		0/19 (0%)
Hypotension	0/175 (0%)		1/102 (1%)		0/44 (0%)		0/19 (0%)
Shock	0/175 (0%)		1/102 (1%)		0/44 (0%)		0/19 (0%)
Other (Not Including Serious) Adverse Events
	Azacitidine		Best Supportive Care Only		Low-dose Cytarabine		Standard Chemotherapy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	175/175 (100%)		86/102 (84.3%)		44/44 (100%)		19/19 (100%)
Blood and lymphatic system disorders
Anaemia	84/175 (48%)		42/102 (41.2%)		19/44 (43.2%)		11/19 (57.9%)
Coagulopathy	0/175 (0%)		0/102 (0%)		0/44 (0%)		2/19 (10.5%)
Febrile neutropenia	6/175 (3.4%)		8/102 (7.8%)		0/44 (0%)		4/19 (21.1%)
Leukopenia	31/175 (17.7%)		2/102 (2%)		3/44 (6.8%)		6/19 (31.6%)
Lymphadenopathy	2/175 (1.1%)		0/102 (0%)		4/44 (9.1%)		0/19 (0%)
Lymphopenia	3/175 (1.7%)		0/102 (0%)		0/44 (0%)		3/19 (15.8%)
Neutropenia	114/175 (65.1%)		29/102 (28.4%)		15/44 (34.1%)		10/19 (52.6%)
Thrombocytopenia	118/175 (67.4%)		34/102 (33.3%)		21/44 (47.7%)		13/19 (68.4%)
Cardiac disorders
Bradycardia	1/175 (0.6%)		0/102 (0%)		0/44 (0%)		1/19 (5.3%)
Bundle branch block right	0/175 (0%)		0/102 (0%)		0/44 (0%)		1/19 (5.3%)
Cardiomegaly	0/175 (0%)		0/102 (0%)		0/44 (0%)		1/19 (5.3%)
Sinus bradycardia	0/175 (0%)		0/102 (0%)		0/44 (0%)		1/19 (5.3%)
Tachycardia	6/175 (3.4%)		0/102 (0%)		1/44 (2.3%)		1/19 (5.3%)
Eye disorders
Chalazion	0/175 (0%)		0/102 (0%)		0/44 (0%)		1/19 (5.3%)
Conjunctival haemorrhage	6/175 (3.4%)		1/102 (1%)		0/44 (0%)		1/19 (5.3%)
Conjunctivitis	2/175 (1.1%)		2/102 (2%)		2/44 (4.5%)		1/19 (5.3%)
Ocular hyperaemia	1/175 (0.6%)		0/102 (0%)		0/44 (0%)		1/19 (5.3%)
Vitreous floaters	0/175 (0%)		0/102 (0%)		0/44 (0%)		1/19 (5.3%)
Gastrointestinal disorders
Abdominal discomfort	2/175 (1.1%)		0/102 (0%)		0/44 (0%)		1/19 (5.3%)
Abdominal pain	21/175 (12%)		7/102 (6.9%)		1/44 (2.3%)		5/19 (26.3%)
Abdominal pain upper	10/175 (5.7%)		3/102 (2.9%)		0/44 (0%)		2/19 (10.5%)
Anal haemorrhage	1/175 (0.6%)		0/102 (0%)		0/44 (0%)		1/19 (5.3%)
Aphthous stomatitis	2/175 (1.1%)		0/102 (0%)		2/44 (4.5%)		1/19 (5.3%)
Constipation	88/175 (50.3%)		8/102 (7.8%)		11/44 (25%)		8/19 (42.1%)
Diarrhoea	38/175 (21.7%)		18/102 (17.6%)		10/44 (22.7%)		12/19 (63.2%)
Dry mouth	5/175 (2.9%)		0/102 (0%)		0/44 (0%)		1/19 (5.3%)
Dyspepsia	10/175 (5.7%)		2/102 (2%)		0/44 (0%)		2/19 (10.5%)
Gastritis	3/175 (1.7%)		3/102 (2.9%)		0/44 (0%)		1/19 (5.3%)
Gastrointestinal pain	1/175 (0.6%)		0/102 (0%)		0/44 (0%)		1/19 (5.3%)
Gastrooesophageal reflux disease	4/175 (2.3%)		0/102 (0%)		0/44 (0%)		2/19 (10.5%)
Gingival bleeding	10/175 (5.7%)		5/102 (4.9%)		2/44 (4.5%)		2/19 (10.5%)
Gingival pain	1/175 (0.6%)		0/102 (0%)		0/44 (0%)		1/19 (5.3%)
Gingivitis	6/175 (3.4%)		4/102 (3.9%)		0/44 (0%)		1/19 (5.3%)
Haemorrhoids	12/175 (6.9%)		5/102 (4.9%)		2/44 (4.5%)		1/19 (5.3%)
Lip haemorrhage	0/175 (0%)		0/102 (0%)		0/44 (0%)		2/19 (10.5%)
Mouth ulceration	9/175 (5.1%)		6/102 (5.9%)		0/44 (0%)		0/19 (0%)
Nausea	84/175 (48%)		12/102 (11.8%)		16/44 (36.4%)		9/19 (47.4%)
Oral discomfort	0/175 (0%)		0/102 (0%)		0/44 (0%)		1/19 (5.3%)
Oral soft tissue disorder	2/175 (1.1%)		1/102 (1%)		0/44 (0%)		1/19 (5.3%)
Rectal haemorrhage	4/175 (2.3%)		3/102 (2.9%)		2/44 (4.5%)		1/19 (5.3%)
Stomatitis	5/175 (2.9%)		1/102 (1%)		0/44 (0%)		2/19 (10.5%)
Vomiting	47/175 (26.9%)		7/102 (6.9%)		5/44 (11.4%)		6/19 (31.6%)
General disorders
Asthenia	27/175 (15.4%)		15/102 (14.7%)		12/44 (27.3%)		2/19 (10.5%)
Catheter site erythema	0/175 (0%)		0/102 (0%)		0/44 (0%)		1/19 (5.3%)
Catheter site haematoma	3/175 (1.7%)		0/102 (0%)		0/44 (0%)		1/19 (5.3%)
Catheter site haemorrhage	1/175 (0.6%)		0/102 (0%)		0/44 (0%)		2/19 (10.5%)
Catheter site pain	2/175 (1.1%)		1/102 (1%)		1/44 (2.3%)		1/19 (5.3%)
Chest pain	9/175 (5.1%)		3/102 (2.9%)		2/44 (4.5%)		4/19 (21.1%)
Chills	5/175 (2.9%)		2/102 (2%)		4/44 (9.1%)		1/19 (5.3%)
Fatigue	42/175 (24%)		11/102 (10.8%)		10/44 (22.7%)		4/19 (21.1%)
Gait disturbance	0/175 (0%)		0/102 (0%)		1/44 (2.3%)		1/19 (5.3%)
General physical health deterioration	3/175 (1.7%)		2/102 (2%)		0/44 (0%)		1/19 (5.3%)
Generalised oedema	1/175 (0.6%)		0/102 (0%)		0/44 (0%)		1/19 (5.3%)
Injection site bruising	9/175 (5.1%)		0/102 (0%)		0/44 (0%)		0/19 (0%)
Injection site erythema	75/175 (42.9%)		0/102 (0%)		0/44 (0%)		0/19 (0%)
Injection site haematoma	11/175 (6.3%)		0/102 (0%)		3/44 (6.8%)		0/19 (0%)
Injection site induration	9/175 (5.1%)		0/102 (0%)		0/44 (0%)		0/19 (0%)
Injection site pain	32/175 (18.3%)		0/102 (0%)		0/44 (0%)		0/19 (0%)
Injection site rash	10/175 (5.7%)		0/102 (0%)		0/44 (0%)		0/19 (0%)
Injection site reaction	51/175 (29.1%)		0/102 (0%)		0/44 (0%)		1/19 (5.3%)
Mucosal inflammation	2/175 (1.1%)		0/102 (0%)		2/44 (4.5%)		4/19 (21.1%)
Oedema	9/175 (5.1%)		5/102 (4.9%)		1/44 (2.3%)		3/19 (15.8%)
Oedema peripheral	23/175 (13.1%)		13/102 (12.7%)		8/44 (18.2%)		3/19 (15.8%)
Pain	7/175 (4%)		2/102 (2%)		1/44 (2.3%)		5/19 (26.3%)
Pitting oedema	3/175 (1.7%)		0/102 (0%)		0/44 (0%)		1/19 (5.3%)
Pyrexia	46/175 (26.3%)		16/102 (15.7%)		17/44 (38.6%)		11/19 (57.9%)
Hepatobiliary disorders
Cholestasis	0/175 (0%)		0/102 (0%)		0/44 (0%)		1/19 (5.3%)
Infections and infestations
Aspergillosis	0/175 (0%)		0/102 (0%)		0/44 (0%)		2/19 (10.5%)
Bacteraemia	0/175 (0%)		0/102 (0%)		0/44 (0%)		2/19 (10.5%)
Bacteriuria	0/175 (0%)		0/102 (0%)		1/44 (2.3%)		1/19 (5.3%)
Bronchitis	16/175 (9.1%)		8/102 (7.8%)		3/44 (6.8%)		0/19 (0%)
Catheter related infection	1/175 (0.6%)		0/102 (0%)		0/44 (0%)		2/19 (10.5%)
Catheter site infection	0/175 (0%)		0/102 (0%)		0/44 (0%)		2/19 (10.5%)
Clostridial infection	0/175 (0%)		0/102 (0%)		0/44 (0%)		1/19 (5.3%)
Enterobacter infection	1/175 (0.6%)		0/102 (0%)		0/44 (0%)		1/19 (5.3%)
Escherichia bacteraemia	0/175 (0%)		0/102 (0%)		0/44 (0%)		1/19 (5.3%)
Fungal skin infection	1/175 (0.6%)		0/102 (0%)		0/44 (0%)		1/19 (5.3%)
Influenza	10/175 (5.7%)		5/102 (4.9%)		1/44 (2.3%)		0/19 (0%)
Klebsiella bacteraemia	0/175 (0%)		0/102 (0%)		1/44 (2.3%)		1/19 (5.3%)
Nail infection	0/175 (0%)		0/102 (0%)		0/44 (0%)		1/19 (5.3%)
Nasopharyngitis	33/175 (18.9%)		13/102 (12.7%)		3/44 (6.8%)		0/19 (0%)
Oral candidiasis	11/175 (6.3%)		5/102 (4.9%)		2/44 (4.5%)		1/19 (5.3%)
Oral herpes	17/175 (9.7%)		5/102 (4.9%)		1/44 (2.3%)		3/19 (15.8%)
Pharyngeal candidiasis	0/175 (0%)		0/102 (0%)		0/44 (0%)		1/19 (5.3%)
Pharyngitis	8/175 (4.6%)		2/102 (2%)		1/44 (2.3%)		1/19 (5.3%)
Pneumonia	2/175 (1.1%)		0/102 (0%)		3/44 (6.8%)		1/19 (5.3%)
Pseudomonas infection	0/175 (0%)		0/102 (0%)		0/44 (0%)		1/19 (5.3%)
Respiratory tract infection	5/175 (2.9%)		3/102 (2.9%)		0/44 (0%)		1/19 (5.3%)
Rhinitis	10/175 (5.7%)		1/102 (1%)		1/44 (2.3%)		1/19 (5.3%)
Sinusitis	6/175 (3.4%)		1/102 (1%)		0/44 (0%)		1/19 (5.3%)
Staphylococcal infection	1/175 (0.6%)		0/102 (0%)		1/44 (2.3%)		1/19 (5.3%)
Upper respiratory tract infection	15/175 (8.6%)		4/102 (3.9%)		0/44 (0%)		0/19 (0%)
Urinary tract infection	12/175 (6.9%)		3/102 (2.9%)		1/44 (2.3%)		0/19 (0%)
Viral upper respiratory tract infection	1/175 (0.6%)		0/102 (0%)		0/44 (0%)		1/19 (5.3%)
Injury, poisoning and procedural complications
Contusion	14/175 (8%)		5/102 (4.9%)		1/44 (2.3%)		0/19 (0%)
Fall	5/175 (2.9%)		0/102 (0%)		3/44 (6.8%)		0/19 (0%)
Overdose	0/175 (0%)		0/102 (0%)		0/44 (0%)		1/19 (5.3%)
Procedural pain	4/175 (2.3%)		0/102 (0%)		0/44 (0%)		1/19 (5.3%)
Scratch	1/175 (0.6%)		1/102 (1%)		0/44 (0%)		1/19 (5.3%)
Thermal burn	1/175 (0.6%)		0/102 (0%)		0/44 (0%)		1/19 (5.3%)
Transfusion reaction	19/175 (10.9%)		5/102 (4.9%)		3/44 (6.8%)		1/19 (5.3%)
Investigations
Alanine aminotransferase increased	5/175 (2.9%)		0/102 (0%)		1/44 (2.3%)		1/19 (5.3%)
Aspartate aminotransferase increased	2/175 (1.1%)		0/102 (0%)		1/44 (2.3%)		1/19 (5.3%)
Blood lactate dehydrogenase increased	1/175 (0.6%)		0/102 (0%)		0/44 (0%)		1/19 (5.3%)
Blood potassium decreased	0/175 (0%)		0/102 (0%)		0/44 (0%)		2/19 (10.5%)
International normalised ratio increased	0/175 (0%)		0/102 (0%)		0/44 (0%)		1/19 (5.3%)
Weight decreased	14/175 (8%)		0/102 (0%)		2/44 (4.5%)		4/19 (21.1%)
Metabolism and nutrition disorders
Anorexia	25/175 (14.3%)		9/102 (8.8%)		5/44 (11.4%)		5/19 (26.3%)
Hypermagnesaemia	0/175 (0%)		0/102 (0%)		0/44 (0%)		1/19 (5.3%)
Hyperuricaemia	4/175 (2.3%)		2/102 (2%)		0/44 (0%)		1/19 (5.3%)
Hypoalbuminaemia	1/175 (0.6%)		1/102 (1%)		0/44 (0%)		1/19 (5.3%)
Hypocalcaemia	2/175 (1.1%)		0/102 (0%)		0/44 (0%)		2/19 (10.5%)
Hypokalaemia	11/175 (6.3%)		2/102 (2%)		1/44 (2.3%)		8/19 (42.1%)
Hypomagnesaemia	0/175 (0%)		0/102 (0%)		0/44 (0%)		2/19 (10.5%)
Hyponatraemia	1/175 (0.6%)		0/102 (0%)		0/44 (0%)		1/19 (5.3%)
Hypophosphataemia	1/175 (0.6%)		0/102 (0%)		1/44 (2.3%)		1/19 (5.3%)
Musculoskeletal and connective tissue disorders
Arthralgia	15/175 (8.6%)		8/102 (7.8%)		2/44 (4.5%)		1/19 (5.3%)
Back pain	15/175 (8.6%)		7/102 (6.9%)		4/44 (9.1%)		5/19 (26.3%)
Bone pain	7/175 (4%)		5/102 (4.9%)		3/44 (6.8%)		0/19 (0%)
Bursitis	1/175 (0.6%)		0/102 (0%)		0/44 (0%)		2/19 (10.5%)
Chondrocalcinosis pyrophosphate	0/175 (0%)		0/102 (0%)		0/44 (0%)		1/19 (5.3%)
Joint swelling	1/175 (0.6%)		2/102 (2%)		1/44 (2.3%)		1/19 (5.3%)
Muscle spasms	10/175 (5.7%)		5/102 (4.9%)		3/44 (6.8%)		0/19 (0%)
Muscular weakness	3/175 (1.7%)		0/102 (0%)		0/44 (0%)		1/19 (5.3%)
Musculoskeletal chest pain	1/175 (0.6%)		2/102 (2%)		1/44 (2.3%)		1/19 (5.3%)
Musculoskeletal pain	9/175 (5.1%)		3/102 (2.9%)		1/44 (2.3%)		3/19 (15.8%)
Neck pain	2/175 (1.1%)		1/102 (1%)		0/44 (0%)		2/19 (10.5%)
Pain in extremity	11/175 (6.3%)		4/102 (3.9%)		4/44 (9.1%)		4/19 (21.1%)
Nervous system disorders
Dizziness	17/175 (9.7%)		7/102 (6.9%)		2/44 (4.5%)		2/19 (10.5%)
Headache	25/175 (14.3%)		8/102 (7.8%)		6/44 (13.6%)		6/19 (31.6%)
Lethargy	13/175 (7.4%)		2/102 (2%)		0/44 (0%)		0/19 (0%)
Sinus headache	2/175 (1.1%)		0/102 (0%)		0/44 (0%)		1/19 (5.3%)
Syncope	4/175 (2.3%)		1/102 (1%)		1/44 (2.3%)		2/19 (10.5%)
Psychiatric disorders
Anxiety	9/175 (5.1%)		1/102 (1%)		2/44 (4.5%)		3/19 (15.8%)
Depression	9/175 (5.1%)		3/102 (2.9%)		2/44 (4.5%)		1/19 (5.3%)
Hallucination	1/175 (0.6%)		0/102 (0%)		0/44 (0%)		1/19 (5.3%)
Insomnia	15/175 (8.6%)		3/102 (2.9%)		5/44 (11.4%)		4/19 (21.1%)
Sleep disorder	6/175 (3.4%)		0/102 (0%)		0/44 (0%)		3/19 (15.8%)
Renal and urinary disorders
Chromaturia	1/175 (0.6%)		0/102 (0%)		1/44 (2.3%)		1/19 (5.3%)
Haematuria	10/175 (5.7%)		1/102 (1%)		0/44 (0%)		2/19 (10.5%)
Haemoglobinuria	0/175 (0%)		0/102 (0%)		0/44 (0%)		1/19 (5.3%)
Nephropathy toxic	0/175 (0%)		0/102 (0%)		0/44 (0%)		1/19 (5.3%)
Proteinuria	1/175 (0.6%)		0/102 (0%)		0/44 (0%)		1/19 (5.3%)
Urethral obstruction	0/175 (0%)		0/102 (0%)		0/44 (0%)		1/19 (5.3%)
Reproductive system and breast disorders
Prostatitis	0/175 (0%)		0/102 (0%)		0/44 (0%)		1/19 (5.3%)
Testicular swelling	0/175 (0%)		0/102 (0%)		0/44 (0%)		1/19 (5.3%)
Vaginal inflammation	0/175 (0%)		0/102 (0%)		0/44 (0%)		1/19 (5.3%)
Respiratory, thoracic and mediastinal disorders
Cough	34/175 (19.4%)		15/102 (14.7%)		5/44 (11.4%)		6/19 (31.6%)
Dyspnoea	26/175 (14.9%)		5/102 (4.9%)		7/44 (15.9%)		3/19 (15.8%)
Dyspnoea exertional	9/175 (5.1%)		1/102 (1%)		2/44 (4.5%)		0/19 (0%)
Epistaxis	26/175 (14.9%)		14/102 (13.7%)		6/44 (13.6%)		3/19 (15.8%)
Hypoxia	1/175 (0.6%)		0/102 (0%)		0/44 (0%)		1/19 (5.3%)
Nasal congestion	3/175 (1.7%)		0/102 (0%)		0/44 (0%)		3/19 (15.8%)
Pharyngolaryngeal pain	11/175 (6.3%)		3/102 (2.9%)		2/44 (4.5%)		1/19 (5.3%)
Pleural effusion	1/175 (0.6%)		2/102 (2%)		0/44 (0%)		1/19 (5.3%)
Pleurisy	1/175 (0.6%)		1/102 (1%)		0/44 (0%)		1/19 (5.3%)
Pneumonitis	1/175 (0.6%)		0/102 (0%)		0/44 (0%)		1/19 (5.3%)
Productive cough	5/175 (2.9%)		2/102 (2%)		1/44 (2.3%)		1/19 (5.3%)
Pulmonary oedema	1/175 (0.6%)		0/102 (0%)		1/44 (2.3%)		2/19 (10.5%)
Skin and subcutaneous tissue disorders
Alopecia	7/175 (4%)		0/102 (0%)		0/44 (0%)		3/19 (15.8%)
Dermatitis allergic	1/175 (0.6%)		1/102 (1%)		0/44 (0%)		2/19 (10.5%)
Ecchymosis	8/175 (4.6%)		7/102 (6.9%)		2/44 (4.5%)		0/19 (0%)
Erythema	13/175 (7.4%)		3/102 (2.9%)		1/44 (2.3%)		2/19 (10.5%)
Erythema nodosum	0/175 (0%)		0/102 (0%)		0/44 (0%)		1/19 (5.3%)
Petechiae	20/175 (11.4%)		4/102 (3.9%)		7/44 (15.9%)		3/19 (15.8%)
Pruritus	20/175 (11.4%)		2/102 (2%)		2/44 (4.5%)		3/19 (15.8%)
Purpura	4/175 (2.3%)		1/102 (1%)		2/44 (4.5%)		1/19 (5.3%)
Rash	18/175 (10.3%)		1/102 (1%)		1/44 (2.3%)		5/19 (26.3%)
Rash macular	1/175 (0.6%)		1/102 (1%)		1/44 (2.3%)		1/19 (5.3%)
Rash papular	1/175 (0.6%)		1/102 (1%)		0/44 (0%)		1/19 (5.3%)
Rash pruritic	2/175 (1.1%)		0/102 (0%)		1/44 (2.3%)		1/19 (5.3%)
Skin lesion	7/175 (4%)		3/102 (2.9%)		0/44 (0%)		2/19 (10.5%)
Urticaria	2/175 (1.1%)		1/102 (1%)		1/44 (2.3%)		1/19 (5.3%)
Vascular disorders
Arteriosclerosis	0/175 (0%)		0/102 (0%)		0/44 (0%)		1/19 (5.3%)
Haematoma	21/175 (12%)		10/102 (9.8%)		6/44 (13.6%)		1/19 (5.3%)
Hypertension	15/175 (8.6%)		4/102 (3.9%)		6/44 (13.6%)		3/19 (15.8%)
Hypotension	10/175 (5.7%)		2/102 (2%)		0/44 (0%)		4/19 (21.1%)
Jugular vein thrombosis	0/175 (0%)		0/102 (0%)		0/44 (0%)		1/19 (5.3%)
Pallor	4/175 (2.3%)		1/102 (1%)		0/44 (0%)		1/19 (5.3%)
Peripheral vascular disorder	2/175 (1.1%)		0/102 (0%)		0/44 (0%)		1/19 (5.3%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The investigator shall have the right to publish and/or present study data provided that the investigator shall (i) furnish the sponsor a copy of any proposed publication or presentation generally thirty (30) days in advance of the submission, (ii) delete any confidential information of the sponsor, and (iii) delay submission for generally up to ninety (90) days to permit the preparation and filing of intellectual property applications or until sponsor gives its consent in a timely manner.

Results Point of Contact

Name/Title	CL Beach
Organization	Celgene Corporation
Phone
Email	CLBeach@celgene.com

Responsible Party:

Celgene

ClinicalTrials.gov Identifier:

NCT00071799

Other Study ID Numbers:

AZA PH GL 2003 CL001

First Posted:

Nov 5, 2003

Last Update Posted:

Oct 29, 2019

Last Verified:

Oct 1, 2019