Phase 3 Randomized, Open-Label Study of Guadecitabine vs... | NCT02920008

Status Module

Description Module

Label	Type	Description	Intervention Names
guadecitabine	Experimental	Guadecitabine will be given SC at a dose of 60 mg/m^2 in 28-day cycles (delayed as necessary to allow blood count recovery).	Drug: guadecitabine
Treatment Choice (TC)	Active Comparator	High intensity Low intensity Best supportive care (BSC).	Drug: Treatment Choice (TC)

Name	Type	Description	Arm Group Labels	Other Names
guadecitabine	Drug	In Cycle 1, guadecitabine will be given for 10 days on Days 1-5 and Days 8-12. In Cycle 2, the guadecitabine dose will be 60 mg/m^2 for either 10 days (Days 1-5 and 8-12) or 5 days (Days 1-5 only) based on assessment of disease response, and hematological recovery by Day ≥28.

Measure	Description	Time Frame
Overall Survival	Overall survival is defined as number of days from day of randomization to date of death, regardless of cause.	From the date of randomization until the date of death, or approximately 34 months

Measure	Description	Time Frame
Event-Free Survival	Event-free survival is defined as number of days from randomization to earliest date of treatment discontinuation (for reasons other than initiation of hematopoietic cell transplant [HCT]), start of alternative anti-leukemia therapy (except HCT), or death.	From the date of randomization until the date of death, or approximately 38 months

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Adult participants ≥18 years of age who are able to understand study procedures, comply with them, and provide written informed consent before any study-specific procedure.
History of cytologically or histologically confirmed diagnosis of AML (except acute promyelocytic leukemia) according to the 2008 World Health Organization (WHO) classification (bone marrow [BM] or peripheral blood [PB] blast counts ≥20%).
Performance status (Eastern Cooperative Oncology Group; ECOG) of 0-2.
Participants with AML previously treated with initial induction therapy using a standard intensive chemotherapy regimen, including cytarabine and an anthracycline, and who are refractory to initial induction (primary refractory) or in relapse after such initial induction with or without prior HCT.
Participants must have either PB or BM blasts ≥5% at time of randomization.
Creatinine clearance or glomerular filtration rate ≥30 mL/min as estimated by the Cockroft-Gault (C-G) or other medically acceptable formulas, such as MDRD (Modification of Diet in Renal Disease) or CKD-EPI (the Chronic Kidney Disease Epidemiology Collaboration).
Women of child-bearing potential must not be pregnant or breastfeeding and must have a negative pregnancy test at screening. Women of child-bearing potential and men with female partners of child-bearing potential must agree to practice 2 highly effective contraceptive measures of birth control and must agree not to become pregnant or father a child (a) while receiving treatment of guadecitabine, decitabine, or azacitidine and for at least 3 months after completing treatment and (b) while receiving treatment with high-intensity TC or LDAC and for at least 6 months after completing treatment.

Exclusion Criteria:

Known clinically active central nervous system (CNS) or extramedullary AML, except leukemia cutis.
Participants who are in first relapse after initial induction, if they had a response duration of >12 months from date when first response first documented or if they are good candidates for HCT.
BCR-ABL-positive leukemia (chronic myelogenous leukemia in blast crisis).
Second malignancy currently requiring active therapy, except breast or prostate cancer stable on or responding to endocrine therapy.
Grade 3 or higher Graft Versus Host Disease (GVHD), or GVHD on either a calcineurin inhibitor or prednisone more than 5 mg/day.
Prior treatment with guadecitabine for any indication, or more than 2 cycles of prior decitabine or azacitidine.
Hypersensitivity to decitabine, guadecitabine, or any of their excipients.
Treated with any investigational therapy within 2 weeks of the first dose of study treatment.
Total serum bilirubin >2.5 × upper limit of normal (ULN; except for participants with Gilbert's Syndrome for whom direct bilirubin is <2.5 × ULN), or liver cirrhosis, or chronic liver disease Child-Pugh Class B or C.
Known active human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV) infection. Inactive hepatitis carrier status or low viral hepatitis titer on antivirals is allowed.
Known significant mental illness or other condition such as active alcohol or other substance abuse or addiction that, in the opinion of the investigator, predisposes the participant to high risk of noncompliance with the protocol.
Refractory congestive heart failure unresponsive to medical treatment; active infection resistant to all antibiotics; or non-AML-associated pulmonary disease requiring >2 liters per minute (LPM) oxygen, or any other condition that puts the participant at an imminent risk of death.
Participants with high PB blasts >50% AND poor ECOG PS of 2.

Name	Affiliation	Role
Harold N Keer, MD, PhD	Astex Pharmaceuticals, Inc.	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
University of Southern California		Los Angeles	California	90033	United States
The University of Chicago Medical Center

PubMed Identifier	Type	Citation	Retractions
38231126	Derived	Roboz GJ, Sanz G, Griffiths EA, Yee K, Kantarjian H, Recher C, Byrne MT, Patkowska E, Kim HJ, Thomas X, Moors I, Stock W, Illes A, Fenaux P, Miyazaki Y, Yamauchi T, O'Connell CL, Hao Y, Keer HN, Azab M, Dohner H. Guadecitabine vs TC in relapsed/refractory AML after intensive chemotherapy: a randomized phase 3 ASTRAL-2 trial. Blood Adv. 2024 Apr 23;8(8):2020-2029. doi: 10.1182/bloodadvances.2023012062.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Guadecitabine	Guadecitabine was administered subcutaneously (SC) at a dose of 60 milligrams per meter square (mg/m^2) for 10 days on Days 1-5 and Days 8-12 or on Days 1-10 in the first cycle. Second cycle was 60 mg/m^2 for either 10 days (Days 1-5 and 8-12 or Days 1-10) or 5 days (Days 1-5 only) based on assessment of disease response, and hematological recovery by end of Cycle 1. For Cycles ≥3, guadecitabine, 60 mg/m^2 was given for 5 days only (Days 1-5). Each cycle = 28 days.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Oct 29, 2018	Jan 11, 2023

Arm/Group Information

ID	Title	Description
BG000	Guadecitabine	Guadecitabine was administered SC at a dose of 60 mg/m^2 for 10 days on Days 1-5 and Days 8-12 or on Days 1-10 in the first cycle. Second cycle was 60 mg/m^2 for either 10 days (Days 1-5 and 8-12 or Days 1-10) or 5 days (Days 1-5 only) based on assessment of disease response, and hematological recovery by end of Cycle 1. For Cycles ≥3, guadecitabine, 60 mg/m^2 was given for 5 days only (Days 1-5). Each cycle = 28 days.
BG001	Treatment Choice (TC)	Intermediate or HiDAC, MEC, and FLAG/FLAG-Ida, LDAC, decitabine, azacitidine, or BSC was administered only. High intensity: Intermediate or HiDAC, recommended as 1-1.5 g/m^2 every 12 hours or up to 6 g/m^2/day for ≤6 days, maximum 36 g/m^2 per cycle; MEC: For example: mitoxantrone 6-12 mg/m^2 IV (recommended 8 mg/m^2), etoposide 80-200 mg/m^2 IV (recommended 100 mg/m^2), and cytarabine 1000 mg/m^2 IV; each daily for 5 days (Days 1-5); FLAG/FLAG-Ida: For example: fludarabine 25-30 mg/m^2 IV daily Days 1-5; cytarabine 1-2 g/m^2 IV daily for up to 5 days (recommended to be given for 4 hours after fludarabine); G-CSF SC daily from Day 6 up to white cell count recovery with or without idarubicin 8 mg/m^2 IV daily on Days 3 to 5. Low intensity: LDAC 20 mg SC or IV twice daily on Days 1-10; Decitabine 20 mg/m^2 IV daily on Days 1-5; Azacitidine 75 mg/m^2 IV or SC daily on Days 1-7. Best supportive care only.
BG002	Total	Total of all reporting groups

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Overall Survival

Overall survival is defined as number of days from day of randomization to date of death, regardless of cause.

The efficacy analysis set included data from all participants randomly assigned to study treatment.

Posted

Median

95% Confidence Interval

days

From the date of randomization until the date of death, or approximately 34 months

ID	Title	Description
OG000	Guadecitabine	Guadecitabine was administered SC at a dose of 60 mg/m^2 for 10 days on Days 1-5 and Days 8-12 or on Days 1-10 in the first cycle. Second cycle was 60 mg/m^2 for either 10 days (Days 1-5 and 8-12 or Days 1-10) or 5 days (Days 1-5 only) based on assessment of disease response, and hematological recovery by end of Cycle 1. For Cycles ≥3, guadecitabine, 60 mg/m^2 was given for 5 days only (Days 1-5). Each cycle = 28 days.
OG001	Treatment Choice (TC)	Intermediate or HiDAC, MEC, and FLAG/FLAG-Ida, LDAC, decitabine, azacitidine, or BSC was administered only. High intensity: Intermediate or HiDAC, recommended as 1-1.5 g/m^2 every 12 hours or up to 6 g/m^2/day for ≤6 days, maximum 36 g/m^2 per cycle; MEC: For example: mitoxantrone 6-12 mg/m^2 IV (recommended 8 mg/m^2), etoposide 80-200 mg/m^2 IV (recommended 100 mg/m^2), and cytarabine 1000 mg/m^2 IV; each daily for 5 days (Days 1-5); FLAG/FLAG-Ida: For example: fludarabine 25-30 mg/m^2 IV daily Days 1-5; cytarabine 1-2 g/m^2 IV daily for up to 5 days (recommended to be given for 4 hours after fludarabine); G-CSF SC daily from Day 6 up to white cell count recovery with or without idarubicin 8 mg/m^2 IV daily on Days 3 to 5. Low intensity: LDAC 20 mg SC or IV twice daily on Days 1-10; Decitabine 20 mg/m^2 IV daily on Days 1-5; Azacitidine 75 mg/m^2 IV or SC daily on Days 1-7. Best supportive care only.

Units	Counts
Participants	OG000148 OG001154

Title

Denominators

Categories

Title	Measurements
	OG000191.0(141.0 to 253.0) OG001163.0(131.0 to 213.0)

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		Stratified log-rank		= 0.3287														Superiority

Secondary

Event-Free Survival

Event-free survival is defined as number of days from randomization to earliest date of treatment discontinuation (for reasons other than initiation of hematopoietic cell transplant [HCT]), start of alternative anti-leukemia therapy (except HCT), or death.

The efficacy analysis set included data from all participants randomly assigned to study treatment.

Posted

Median

95% Confidence Interval

days

From the date of randomization until the date of death, or approximately 38 months

ID	Title	Description
OG000	Guadecitabine	Guadecitabine was administered SC at a dose of 60 mg/m^2 for 10 days on Days 1-5 and Days 8-12 or on Days 1-10 in the first cycle. Second cycle was 60 mg/m^2 for either 10 days (Days 1-5 and 8-12 or Days 1-10) or 5 days (Days 1-5 only) based on assessment of disease response, and hematological recovery by end of Cycle 1. For Cycles ≥3, guadecitabine, 60 mg/m^2 was given for 5 days only (Days 1-5). Each cycle = 28 days.
OG001	Treatment Choice (TC)	Intermediate or HiDAC, MEC, and FLAG/FLAG-Ida, LDAC, decitabine, azacitidine, or BSC was administered only. High intensity: Intermediate or HiDAC, recommended as 1-1.5 g/m^2 every 12 hours or up to 6 g/m^2/day for ≤6 days, maximum 36 g/m^2 per cycle; MEC: For example: mitoxantrone 6-12 mg/m^2 IV (recommended 8 mg/m^2), etoposide 80-200 mg/m^2 IV (recommended 100 mg/m^2), and cytarabine 1000 mg/m^2 IV; each daily for 5 days (Days 1-5); FLAG/FLAG-Ida: For example: fludarabine 25-30 mg/m^2 IV daily Days 1-5; cytarabine 1-2 g/m^2 IV daily for up to 5 days (recommended to be given for 4 hours after fludarabine); G-CSF SC daily from Day 6 up to white cell count recovery with or without idarubicin 8 mg/m^2 IV daily on Days 3 to 5. Low intensity: LDAC 20 mg SC or IV twice daily on Days 1-10; Decitabine 20 mg/m^2 IV daily on Days 1-5; Azacitidine 75 mg/m^2 IV or SC daily on Days 1-7. Best supportive care only.

Secondary

Long-Term Survival

Survival rate at 1 year after randomization; participants were also followed to estimate 2-year survival rate.

The efficacy analysis set included data from all participants randomly assigned to study treatment.

Posted

Number

95% Confidence Interval

proportion

Up to approximately 38 months

ID	Title	Description
OG000	Guadecitabine	Guadecitabine was administered SC at a dose of 60 mg/m^2 for 10 days on Days 1-5 and Days 8-12 or on Days 1-10 in the first cycle. Second cycle was 60 mg/m^2 for either 10 days (Days 1-5 and 8-12 or Days 1-10) or 5 days (Days 1-5 only) based on assessment of disease response, and hematological recovery by end of Cycle 1. For Cycles ≥3, guadecitabine, 60 mg/m^2 was given for 5 days only (Days 1-5). Each cycle = 28 days.
OG001	Treatment Choice (TC)	Intermediate or HiDAC, MEC, and FLAG/FLAG-Ida, LDAC, decitabine, azacitidine, or BSC was administered only. High intensity: Intermediate or HiDAC, recommended as 1-1.5 g/m^2 every 12 hours or up to 6 g/m^2/day for ≤6 days, maximum 36 g/m^2 per cycle; MEC: For example: mitoxantrone 6-12 mg/m^2 IV (recommended 8 mg/m^2), etoposide 80-200 mg/m^2 IV (recommended 100 mg/m^2), and cytarabine 1000 mg/m^2 IV; each daily for 5 days (Days 1-5); FLAG/FLAG-Ida: For example: fludarabine 25-30 mg/m^2 IV daily Days 1-5; cytarabine 1-2 g/m^2 IV daily for up to 5 days (recommended to be given for 4 hours after fludarabine); G-CSF SC daily from Day 6 up to white cell count recovery with or without idarubicin 8 mg/m^2 IV daily on Days 3 to 5. Low intensity: LDAC 20 mg SC or IV twice daily on Days 1-10; Decitabine 20 mg/m^2 IV daily on Days 1-5; Azacitidine 75 mg/m^2 IV or SC daily on Days 1-7. Best supportive care only.

Secondary

Number of Days Alive and Out of the Hospital (NDAOH)

Number of days participants alive and out of hospital during first 6 months of the study.

The efficacy analysis set included data from all participants randomly assigned to study treatment.

Posted

Geometric Least Squares Mean

95% Confidence Interval

days

6 months

ID	Title	Description
OG000	Guadecitabine	Guadecitabine was administered SC at a dose of 60 mg/m^2 for 10 days on Days 1-5 and Days 8-12 or on Days 1-10 in the first cycle. Second cycle was 60 mg/m^2 for either 10 days (Days 1-5 and 8-12 or Days 1-10) or 5 days (Days 1-5 only) based on assessment of disease response, and hematological recovery by end of Cycle 1. For Cycles ≥3, guadecitabine, 60 mg/m^2 was given for 5 days only (Days 1-5). Each cycle = 28 days.
OG001	Treatment Choice (TC)	Intermediate or HiDAC, MEC, and FLAG/FLAG-Ida, LDAC, decitabine, azacitidine, or BSC was administered only. High intensity: Intermediate or HiDAC, recommended as 1-1.5 g/m^2 every 12 hours or up to 6 g/m^2/day for ≤6 days, maximum 36 g/m^2 per cycle; MEC: For example: mitoxantrone 6-12 mg/m^2 IV (recommended 8 mg/m^2), etoposide 80-200 mg/m^2 IV (recommended 100 mg/m^2), and cytarabine 1000 mg/m^2 IV; each daily for 5 days (Days 1-5); FLAG/FLAG-Ida: For example: fludarabine 25-30 mg/m^2 IV daily Days 1-5; cytarabine 1-2 g/m^2 IV daily for up to 5 days (recommended to be given for 4 hours after fludarabine); G-CSF SC daily from Day 6 up to white cell count recovery with or without idarubicin 8 mg/m^2 IV daily on Days 3 to 5. Low intensity: LDAC 20 mg SC or IV twice daily on Days 1-10; Decitabine 20 mg/m^2 IV daily on Days 1-5; Azacitidine 75 mg/m^2 IV or SC daily on Days 1-7. Best supportive care only.

Secondary

Transfusion Independence Rate

Number of participants without red blood cells (RBC) or platelet transfusion for any 8-week period after treatment divided by total number of participants in efficacy analysis.

The efficacy analysis set included data from all participants randomly assigned to study treatment.

Posted

Number

percentage of participants

Baseline up to approximately 38 months

ID	Title	Description
OG000	Guadecitabine	Guadecitabine was administered SC at a dose of 60 mg/m^2 for 10 days on Days 1-5 and Days 8-12 or on Days 1-10 in the first cycle. Second cycle was 60 mg/m^2 for either 10 days (Days 1-5 and 8-12 or Days 1-10) or 5 days (Days 1-5 only) based on assessment of disease response, and hematological recovery by end of Cycle 1. For Cycles ≥3, guadecitabine, 60 mg/m^2 was given for 5 days only (Days 1-5). Each cycle = 28 days.
OG001	Treatment Choice (TC)	Intermediate or HiDAC, MEC, and FLAG/FLAG-Ida, LDAC, decitabine, azacitidine, or BSC was administered only. High intensity: Intermediate or HiDAC, recommended as 1-1.5 g/m^2 every 12 hours or up to 6 g/m^2/day for ≤6 days, maximum 36 g/m^2 per cycle; MEC: For example: mitoxantrone 6-12 mg/m^2 IV (recommended 8 mg/m^2), etoposide 80-200 mg/m^2 IV (recommended 100 mg/m^2), and cytarabine 1000 mg/m^2 IV; each daily for 5 days (Days 1-5); FLAG/FLAG-Ida: For example: fludarabine 25-30 mg/m^2 IV daily Days 1-5; cytarabine 1-2 g/m^2 IV daily for up to 5 days (recommended to be given for 4 hours after fludarabine); G-CSF SC daily from Day 6 up to white cell count recovery with or without idarubicin 8 mg/m^2 IV daily on Days 3 to 5. Low intensity: LDAC 20 mg SC or IV twice daily on Days 1-10; Decitabine 20 mg/m^2 IV daily on Days 1-5; Azacitidine 75 mg/m^2 IV or SC daily on Days 1-7. Best supportive care only.

Secondary

Complete Response Rate

The Complete response (CR) rate based on modified International Working Group (IWG) 2003 AML Response Criteria was calculated as the number of participants with a best response of CR divided by the total number of participants included in the efficacy analysis. CR as per modified 2003 IWG AML Response Criteria is absolute neutrophil count (ANC) ≥1000/μL, platelets ≥100,000/μL, independence from red blood cells (RBC) and platelet transfusions over the past week, no leukemic blasts in peripheral blood and bone marrow should contain less than 5% blast cells.

The efficacy analysis set included data from all participants randomly assigned to study treatment.

Posted

Number

percentage of participants

Baseline to end of treatment, or approximately 38 months

ID	Title	Description
OG000	Guadecitabine	Guadecitabine was administered SC at a dose of 60 mg/m^2 for 10 days on Days 1-5 and Days 8-12 or on Days 1-10 in the first cycle. Second cycle was 60 mg/m^2 for either 10 days (Days 1-5 and 8-12 or Days 1-10) or 5 days (Days 1-5 only) based on assessment of disease response, and hematological recovery by end of Cycle 1. For Cycles ≥3, guadecitabine, 60 mg/m^2 was given for 5 days only (Days 1-5). Each cycle = 28 days.
OG001	Treatment Choice (TC)	Intermediate or HiDAC, MEC, and FLAG/FLAG-Ida, LDAC, decitabine, azacitidine, or BSC was administered only. High intensity: Intermediate or HiDAC, recommended as 1-1.5 g/m^2 every 12 hours or up to 6 g/m^2/day for ≤6 days, maximum 36 g/m^2 per cycle; MEC: For example: mitoxantrone 6-12 mg/m^2 IV (recommended 8 mg/m^2), etoposide 80-200 mg/m^2 IV (recommended 100 mg/m^2), and cytarabine 1000 mg/m^2 IV; each daily for 5 days (Days 1-5); FLAG/FLAG-Ida: For example: fludarabine 25-30 mg/m^2 IV daily Days 1-5; cytarabine 1-2 g/m^2 IV daily for up to 5 days (recommended to be given for 4 hours after fludarabine); G-CSF SC daily from Day 6 up to white cell count recovery with or without idarubicin 8 mg/m^2 IV daily on Days 3 to 5. Low intensity: LDAC 20 mg SC or IV twice daily on Days 1-10; Decitabine 20 mg/m^2 IV daily on Days 1-5; Azacitidine 75 mg/m^2 IV or SC daily on Days 1-7. Best supportive care only.

Secondary

Combined Complete Response and Complete Response With Partial Hematologic Recovery Rate

The combined CR and CR with partial hematologic recovery rate based on modified International Working Group (IWG) 2003 AML Response Criteria was calculated as number of participants with CR and CR with partial hematologic recovery divided by the total number of participants included in the efficacy analysis. CR as per modified 2003 IWG AML Response Criteria is absolute neutrophil count (ANC) ≥1000/μL, platelets ≥100,000/μL, independence from red blood cells (RBC) and platelet transfusions over the past week, no leukemic blasts in peripheral blood and bone marrow should contain less than 5% blast cells.

The efficacy analysis set included data from all participants randomly assigned to study treatment.

Posted

Number

percentage of participants

Baseline to end of treatment, or approximately 38 months

ID	Title	Description
OG000	Guadecitabine	Guadecitabine was administered SC at a dose of 60 mg/m^2 for 10 days on Days 1-5 and Days 8-12 or on Days 1-10 in the first cycle. Second cycle was 60 mg/m^2 for either 10 days (Days 1-5 and 8-12 or Days 1-10) or 5 days (Days 1-5 only) based on assessment of disease response, and hematological recovery by end of Cycle 1. For Cycles ≥3, guadecitabine, 60 mg/m^2 was given for 5 days only (Days 1-5). Each cycle = 28 days.
OG001	Treatment Choice (TC)	Intermediate or HiDAC, MEC, and FLAG/FLAG-Ida, LDAC, decitabine, azacitidine, or BSC was administered only. High intensity: Intermediate or HiDAC, recommended as 1-1.5 g/m^2 every 12 hours or up to 6 g/m^2/day for ≤6 days, maximum 36 g/m^2 per cycle; MEC: For example: mitoxantrone 6-12 mg/m^2 IV (recommended 8 mg/m^2), etoposide 80-200 mg/m^2 IV (recommended 100 mg/m^2), and cytarabine 1000 mg/m^2 IV; each daily for 5 days (Days 1-5); FLAG/FLAG-Ida: For example: fludarabine 25-30 mg/m^2 IV daily Days 1-5; cytarabine 1-2 g/m^2 IV daily for up to 5 days (recommended to be given for 4 hours after fludarabine); G-CSF SC daily from Day 6 up to white cell count recovery with or without idarubicin 8 mg/m^2 IV daily on Days 3 to 5. Low intensity: LDAC 20 mg SC or IV twice daily on Days 1-10; Decitabine 20 mg/m^2 IV daily on Days 1-5; Azacitidine 75 mg/m^2 IV or SC daily on Days 1-7. Best supportive care only.

Secondary

Composite Complete Response Rate

Composite complete response rate based on modified IWG 2003 AML Response Criteria defined as number of participants with best response of CR, CR with incomplete platelet recovery (CRp), or CR with incomplete blood count recovery (CRi) divided by total number of participants in efficacy analysis. CR as per modified 2003 IWG AML Response Criteria is ANC ≥1000/μL, platelets ≥100,000/μL, independence from RBC and platelet transfusions over the past week, no leukemic blasts in peripheral blood and bone marrow should contain less than 5% blast cells. CRp is defined as ANC ≥1000/μL, Platelets <100,000/μL, independence from RBC transfusions over the past week, no leukemic blasts and bone marrow should contain less than 5% blast cells. CRi is defined as ANC <1000/μL, no leukemic blasts and bone marrow should contain less than 5% blast cells.

The efficacy analysis set included data from all participants randomly assigned to study treatment.

Posted

Number

percentage of participants

Baseline to end of treatment, or approximately 38 months

ID	Title	Description
OG000	Guadecitabine	Guadecitabine was administered SC at a dose of 60 mg/m^2 for 10 days on Days 1-5 and Days 8-12 or on Days 1-10 in the first cycle. Second cycle was 60 mg/m^2 for either 10 days (Days 1-5 and 8-12 or Days 1-10) or 5 days (Days 1-5 only) based on assessment of disease response, and hematological recovery by end of Cycle 1. For Cycles ≥3, guadecitabine, 60 mg/m^2 was given for 5 days only (Days 1-5). Each cycle = 28 days.
OG001	Treatment Choice (TC)

Secondary

Hematopoietic Cell Transplant (HCT) Rate

Number of participants who received HCT after randomization divided by total number of participants in efficacy analysis.

The efficacy analysis set included data from all participants randomly assigned to study treatment.

Posted

Number

percentage of participants

Baseline to long term follow-up or approximately 38 months

ID	Title	Description
OG000	Guadecitabine	Guadecitabine was administered SC at a dose of 60 mg/m^2 for 10 days on Days 1-5 and Days 8-12 or on Days 1-10 in the first cycle. Second cycle was 60 mg/m^2 for either 10 days (Days 1-5 and 8-12 or Days 1-10) or 5 days (Days 1-5 only) based on assessment of disease response, and hematological recovery by end of Cycle 1. For Cycles ≥3, guadecitabine, 60 mg/m^2 was given for 5 days only (Days 1-5). Each cycle = 28 days.
OG001	Treatment Choice (TC)	Intermediate or HiDAC, MEC, and FLAG/FLAG-Ida, LDAC, decitabine, azacitidine, or BSC was administered only. High intensity: Intermediate or HiDAC, recommended as 1-1.5 g/m^2 every 12 hours or up to 6 g/m^2/day for ≤6 days, maximum 36 g/m^2 per cycle; MEC: For example: mitoxantrone 6-12 mg/m^2 IV (recommended 8 mg/m^2), etoposide 80-200 mg/m^2 IV (recommended 100 mg/m^2), and cytarabine 1000 mg/m^2 IV; each daily for 5 days (Days 1-5); FLAG/FLAG-Ida: For example: fludarabine 25-30 mg/m^2 IV daily Days 1-5; cytarabine 1-2 g/m^2 IV daily for up to 5 days (recommended to be given for 4 hours after fludarabine); G-CSF SC daily from Day 6 up to white cell count recovery with or without idarubicin 8 mg/m^2 IV daily on Days 3 to 5. Low intensity: LDAC 20 mg SC or IV twice daily on Days 1-10; Decitabine 20 mg/m^2 IV daily on Days 1-5; Azacitidine 75 mg/m^2 IV or SC daily on Days 1-7. Best supportive care only.

Secondary

Duration of Complete Response (CR) + CR With Partial Hematologic Recovery (CRh)

The time from first CR or CRh to time of relapse (the date of the earliest of the following 3 events):

relapse (defined as the earliest time point whereby BM assessment or PB assessment by the investigator indicate relapse/disease progression due to confirmed reappearance of leukemic blasts in PB or ≥5% leukemic blasts in BM, or clinical progression determined by the investigator),
start of alternative therapy (except HCT) or
death.

The efficacy analysis set included data from all participants randomly assigned to study treatment.

Posted

Median

95% Confidence Interval

days

Baseline to end of treatment, or approximately 38 months

ID	Title	Description
OG000	Guadecitabine	Guadecitabine was administered SC at a dose of 60 mg/m^2 for 10 days on Days 1-5 and Days 8-12 or on Days 1-10 in the first cycle. Second cycle was 60 mg/m^2 for either 10 days (Days 1-5 and 8-12 or Days 1-10) or 5 days (Days 1-5 only) based on assessment of disease response, and hematological recovery by end of Cycle 1. For Cycles ≥3, guadecitabine, 60 mg/m^2 was given for 5 days only (Days 1-5). Each cycle = 28 days.
OG001	Treatment Choice (TC)	Intermediate or HiDAC, MEC, and FLAG/FLAG-Ida, LDAC, decitabine, azacitidine, or BSC was administered only. High intensity: Intermediate or HiDAC, recommended as 1-1.5 g/m^2 every 12 hours or up to 6 g/m^2/day for ≤6 days, maximum 36 g/m^2 per cycle; MEC: For example: mitoxantrone 6-12 mg/m^2 IV (recommended 8 mg/m^2), etoposide 80-200 mg/m^2 IV (recommended 100 mg/m^2), and cytarabine 1000 mg/m^2 IV; each daily for 5 days (Days 1-5); FLAG/FLAG-Ida: For example: fludarabine 25-30 mg/m^2 IV daily Days 1-5; cytarabine 1-2 g/m^2 IV daily for up to 5 days (recommended to be given for 4 hours after fludarabine); G-CSF SC daily from Day 6 up to white cell count recovery with or without idarubicin 8 mg/m^2 IV daily on Days 3 to 5. Low intensity: LDAC 20 mg SC or IV twice daily on Days 1-10; Decitabine 20 mg/m^2 IV daily on Days 1-5; Azacitidine 75 mg/m^2 IV or SC daily on Days 1-7. Best supportive care only.

Secondary

Change From Baseline in EuroQoL-5 Dimension 5 Level (EQ-5D-5L) Index Scores

Index score is calculated based on 5-level version of the EQ-5D descriptive system using the value set for England.

The range of index score is from -0.281 (for the worst health state, score of 5 for all categories) to 1 (for the best health state, score of 1 for all categories).

The efficacy analysis set included data from all participants randomly assigned to study treatment. Overall number of participants analyzed is the number of participants with data available for analysis in this outcome measure.

Posted

Geometric Least Squares Mean

95% Confidence Interval

score on a scale

Baseline to 6 months

ID	Title	Description
OG000	Guadecitabine	Guadecitabine was administered SC at a dose of 60 mg/m^2 for 10 days on Days 1-5 and Days 8-12 or on Days 1-10 in the first cycle. Second cycle was 60 mg/m^2 for either 10 days (Days 1-5 and 8-12 or Days 1-10) or 5 days (Days 1-5 only) based on assessment of disease response, and hematological recovery by end of Cycle 1. For Cycles ≥3, guadecitabine, 60 mg/m^2 was given for 5 days only (Days 1-5). Each cycle = 28 days.
OG001	Treatment Choice (TC)	Intermediate or HiDAC, MEC, and FLAG/FLAG-Ida, LDAC, decitabine, azacitidine, or BSC was administered only. High intensity: Intermediate or HiDAC, recommended as 1-1.5 g/m^2 every 12 hours or up to 6 g/m^2/day for ≤6 days, maximum 36 g/m^2 per cycle; MEC: For example: mitoxantrone 6-12 mg/m^2 IV (recommended 8 mg/m^2), etoposide 80-200 mg/m^2 IV (recommended 100 mg/m^2), and cytarabine 1000 mg/m^2 IV; each daily for 5 days (Days 1-5); FLAG/FLAG-Ida: For example: fludarabine 25-30 mg/m^2 IV daily Days 1-5; cytarabine 1-2 g/m^2 IV daily for up to 5 days (recommended to be given for 4 hours after fludarabine); G-CSF SC daily from Day 6 up to white cell count recovery with or without idarubicin 8 mg/m^2 IV daily on Days 3 to 5. Low intensity: LDAC 20 mg SC or IV twice daily on Days 1-10; Decitabine 20 mg/m^2 IV daily on Days 1-5; Azacitidine 75 mg/m^2 IV or SC daily on Days 1-7. Best supportive care only.

Secondary

Change in EQ-5D-5L Visual Analogue Scale (VAS) Score

VAS score is obtained using vertical 20-cm visual analogue scale with the top value of 100 labelled as 'the best health you can imagine' and the bottom value of 0 labelled as 'the worst health you can imagine'.

Posted

Geometric Least Squares Mean

95% Confidence Interval

score on a scale

Baseline to 6 months

ID	Title	Description
OG000	Guadecitabine	Guadecitabine was administered SC at a dose of 60 mg/m^2 for 10 days on Days 1-5 and Days 8-12 or on Days 1-10 in the first cycle. Second cycle was 60 mg/m^2 for either 10 days (Days 1-5 and 8-12 or Days 1-10) or 5 days (Days 1-5 only) based on assessment of disease response, and hematological recovery by end of Cycle 1. For Cycles ≥3, guadecitabine, 60 mg/m^2 was given for 5 days only (Days 1-5). Each cycle = 28 days.
OG001	Treatment Choice (TC)	Intermediate or HiDAC, MEC, and FLAG/FLAG-Ida, LDAC, decitabine, azacitidine, or BSC was administered only. High intensity: Intermediate or HiDAC, recommended as 1-1.5 g/m^2 every 12 hours or up to 6 g/m^2/day for ≤6 days, maximum 36 g/m^2 per cycle; MEC: For example: mitoxantrone 6-12 mg/m^2 IV (recommended 8 mg/m^2), etoposide 80-200 mg/m^2 IV (recommended 100 mg/m^2), and cytarabine 1000 mg/m^2 IV; each daily for 5 days (Days 1-5); FLAG/FLAG-Ida: For example: fludarabine 25-30 mg/m^2 IV daily Days 1-5; cytarabine 1-2 g/m^2 IV daily for up to 5 days (recommended to be given for 4 hours after fludarabine); G-CSF SC daily from Day 6 up to white cell count recovery with or without idarubicin 8 mg/m^2 IV daily on Days 3 to 5. Low intensity: LDAC 20 mg SC or IV twice daily on Days 1-10; Decitabine 20 mg/m^2 IV daily on Days 1-5; Azacitidine 75 mg/m^2 IV or SC daily on Days 1-7. Best supportive care only.

Secondary

Percentage of Participants With Adverse Events (AEs)

An AE is any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can therefore be any unfavorable and unintended sign (including a clinically significant abnormal finding in laboratory tests or other diagnostic procedures), symptom, or disease temporally associated with the use of a drug, without any judgment about causality.

The safety analysis set included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.

Posted

Number

percentage of participants

From first dose until 30 days after the last dose of study drug, or approximately 38 months

ID	Title	Description
OG000	Guadecitabine	Guadecitabine was administered SC at a dose of 60 mg/m^2 for 10 days on Days 1-5 and Days 8-12 or on Days 1-10 in the first cycle. Second cycle was 60 mg/m^2 for either 10 days (Days 1-5 and 8-12 or Days 1-10) or 5 days (Days 1-5 only) based on assessment of disease response, and hematological recovery by end of Cycle 1. For Cycles ≥3, guadecitabine, 60 mg/m^2 was given for 5 days only (Days 1-5). Each cycle = 28 days.
OG001	Treatment Choice (TC)	Intermediate or HiDAC, MEC, and FLAG/FLAG-Ida, LDAC, decitabine, azacitidine, or BSC was administered only. High intensity: Intermediate or HiDAC, recommended as 1-1.5 g/m^2 every 12 hours or up to 6 g/m^2/day for ≤6 days, maximum 36 g/m^2 per cycle; MEC: For example: mitoxantrone 6-12 mg/m^2 IV (recommended 8 mg/m^2), etoposide 80-200 mg/m^2 IV (recommended 100 mg/m^2), and cytarabine 1000 mg/m^2 IV; each daily for 5 days (Days 1-5); FLAG/FLAG-Ida: For example: fludarabine 25-30 mg/m^2 IV daily Days 1-5; cytarabine 1-2 g/m^2 IV daily for up to 5 days (recommended to be given for 4 hours after fludarabine); G-CSF SC daily from Day 6 up to white cell count recovery with or without idarubicin 8 mg/m^2 IV daily on Days 3 to 5. Low intensity: LDAC 20 mg SC or IV twice daily on Days 1-10; Decitabine 20 mg/m^2 IV daily on Days 1-5; Azacitidine 75 mg/m^2 IV or SC daily on Days 1-7. Best supportive care only.

Secondary

All-Cause Mortality

All-cause mortality in the first 30 days and first 60 days after the start of treatment divided by the total number of participants receiving at least one dose of study treatment.

The efficacy analysis set included data from all participants randomly assigned to study treatment.

Posted

Number

percentage of participants

From the first dose until 60 days after the first dose of study drug

ID	Title	Description
OG000	Guadecitabine	Guadecitabine was administered SC at a dose of 60 mg/m^2 for 10 days on Days 1-5 and Days 8-12 or on Days 1-10 in the first cycle. Second cycle was 60 mg/m^2 for either 10 days (Days 1-5 and 8-12 or Days 1-10) or 5 days (Days 1-5 only) based on assessment of disease response, and hematological recovery by end of Cycle 1. For Cycles ≥3, guadecitabine, 60 mg/m^2 was given for 5 days only (Days 1-5). Each cycle = 28 days.
OG001	Treatment Choice (TC)	Intermediate or HiDAC, MEC, and FLAG/FLAG-Ida, LDAC, decitabine, azacitidine, or BSC was administered only. High intensity: Intermediate or HiDAC, recommended as 1-1.5 g/m^2 every 12 hours or up to 6 g/m^2/day for ≤6 days, maximum 36 g/m^2 per cycle; MEC: For example: mitoxantrone 6-12 mg/m^2 IV (recommended 8 mg/m^2), etoposide 80-200 mg/m^2 IV (recommended 100 mg/m^2), and cytarabine 1000 mg/m^2 IV; each daily for 5 days (Days 1-5); FLAG/FLAG-Ida: For example: fludarabine 25-30 mg/m^2 IV daily Days 1-5; cytarabine 1-2 g/m^2 IV daily for up to 5 days (recommended to be given for 4 hours after fludarabine); G-CSF SC daily from Day 6 up to white cell count recovery with or without idarubicin 8 mg/m^2 IV daily on Days 3 to 5. Low intensity: LDAC 20 mg SC or IV twice daily on Days 1-10; Decitabine 20 mg/m^2 IV daily on Days 1-5; Azacitidine 75 mg/m^2 IV or SC daily on Days 1-7. Best supportive care only.

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Guadecitabine	Guadecitabine was administered SC at a dose of 60 mg/m^2 for 10 days on Days 1-5 and Days 8-12 or on Days 1-10 in the first cycle. Second cycle was 60 mg/m^2 for either 10 days (Days 1-5 and 8-12 or Days 1-10) or 5 days (Days 1-5 only) based on assessment of disease response, and hematological recovery by end of Cycle 1. For Cycles ≥3, guadecitabine, 60 mg/m^2 was given for 5 days only (Days 1-5). Each cycle = 28 days.	117	148	113	145	138	145
EG001	Treatment Choice (TC)	Intermediate or HiDAC, MEC, and FLAG/FLAG-Ida, LDAC, decitabine, azacitidine, or BSC was administered only. High intensity: Intermediate or HiDAC, recommended as 1-1.5 g/m^2 every 12 hours or up to 6 g/m^2/day for ≤6 days, maximum 36 g/m^2 per cycle; MEC: For example: mitoxantrone 6-12 mg/m^2 IV (recommended 8 mg/m^2), etoposide 80-200 mg/m^2 IV (recommended 100 mg/m^2), and cytarabine 1000 mg/m^2 IV; each daily for 5 days (Days 1-5); FLAG/FLAG-Ida: For example: fludarabine 25-30 mg/m^2 IV daily Days 1-5; cytarabine 1-2 g/m^2 IV daily for up to 5 days (recommended to be given for 4 hours after fludarabine); G-CSF SC daily from Day 6 up to white cell count recovery with or without idarubicin 8 mg/m^2 IV daily on Days 3 to 5. Low intensity: LDAC 20 mg SC or IV twice daily on Days 1-10; Decitabine 20 mg/m^2 IV daily on Days 1-5; Azacitidine 75 mg/m^2 IV or SC daily on Days 1-7. Best supportive care only.	129	154	91	147	137	147

Serious Adverse Events

Term	Organ System	Assessment Type	Statistical Information
Embolism	Vascular disorders	Systematic Assessment	EG0001 affected145 at risk EG0010 affected147 at risk
Hypotension	Vascular disorders	Systematic Assessment	EG0000 affected145 at risk EG0011 affected147 at risk
Venous thrombosis	Vascular disorders	Systematic Assessment	EG0000 affected145 at risk EG0011 affected147 at risk
Malignant melanoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	Systematic Assessment	EG0001 affected145 at risk EG0010 affected147 at risk
Meningioma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	Systematic Assessment	EG0001 affected145 at risk EG0010 affected147 at risk
Tumour associated fever	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	Systematic Assessment	EG0000 affected145 at risk EG0011 affected147 at risk
Asthenia	General disorders	Systematic Assessment	EG0001 affected145 at risk EG0011 affected147 at risk
General physical health deterioration	General disorders	Systematic Assessment	EG0002 affected145 at risk EG0011 affected147 at risk
Multiple organ dysfunction syndrome	General disorders	Systematic Assessment	EG0001 affected145 at risk EG0010 affected147 at risk
Oedema peripheral	General disorders	Systematic Assessment	EG0001 affected145 at risk EG0010 affected147 at risk
Pyrexia	General disorders	Systematic Assessment	EG0005 affected145 at risk EG0016 affected147 at risk
Suicidal ideation	Psychiatric disorders	Systematic Assessment	EG0001 affected145 at risk EG0010 affected147 at risk
Anaphylactic transfusion reaction	Injury, poisoning and procedural complications	Systematic Assessment	EG0001 affected145 at risk EG0010 affected147 at risk
Contusion	Injury, poisoning and procedural complications	Systematic Assessment	EG0000 affected145 at risk EG0011 affected147 at risk
Ilium fracture	Injury, poisoning and procedural complications	Systematic Assessment	EG0000 affected145 at risk EG0011 affected147 at risk
Postoperative respiratory distress	Injury, poisoning and procedural complications	Systematic Assessment	EG0001 affected145 at risk EG0010 affected147 at risk
Transfusion reaction	Injury, poisoning and procedural complications	Systematic Assessment	EG0002 affected145 at risk EG0010 affected147 at risk
Alanine aminotransferase increased	Investigations	Systematic Assessment	EG0001 affected145 at risk EG0010 affected147 at risk
Aspartate aminotransferase increased	Investigations	Systematic Assessment	EG0001 affected145 at risk EG0010 affected147 at risk
C-reactive protein increased	Investigations	Systematic Assessment	EG0001 affected145 at risk EG0010 affected147 at risk
Electrocardiogram QT prolonged	Investigations	Systematic Assessment	EG0000 affected145 at risk EG0011 affected147 at risk
Gamma-glutamyltransferase increased	Investigations	Systematic Assessment	EG0000 affected145 at risk EG0011 affected147 at risk
Troponin T increased	Investigations	Systematic Assessment	EG0001 affected145 at risk EG0010 affected147 at risk
Acute myocardial infarction	Cardiac disorders	Systematic Assessment	EG0001 affected145 at risk EG0010 affected147 at risk
Atrial fibrillation	Cardiac disorders	Systematic Assessment	EG0001 affected145 at risk EG0011 affected147 at risk
Cardiac arrest	Cardiac disorders	Systematic Assessment	EG0004 affected145 at risk EG0010 affected147 at risk
Cardiac failure	Cardiac disorders	Systematic Assessment	EG0003 affected145 at risk EG0011 affected147 at risk
Cardiac failure acute	Cardiac disorders	Systematic Assessment	EG0002 affected145 at risk EG0010 affected147 at risk
Cardiac failure chronic	Cardiac disorders	Systematic Assessment	EG0000 affected145 at risk EG0011 affected147 at risk
Cardiac failure congestive	Cardiac disorders	Systematic Assessment	EG0000 affected145 at risk EG0011 affected147 at risk
Cardio-respiratory arrest	Cardiac disorders	Systematic Assessment	EG0001 affected145 at risk EG0010 affected147 at risk
Myocardial infarction	Cardiac disorders	Systematic Assessment	EG0001 affected145 at risk EG0011 affected147 at risk
Pericardial effusion	Cardiac disorders	Systematic Assessment	EG0000 affected145 at risk EG0012 affected147 at risk
Aplasia	Congenital, familial and genetic disorders	Systematic Assessment	EG0000 affected145 at risk EG0011 affected147 at risk
Acute pulmonary oedema	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0001 affected145 at risk EG0011 affected147 at risk
Acute respiratory distress syndrome	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0002 affected145 at risk EG0010 affected147 at risk
Acute respiratory failure	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0001 affected145 at risk EG0010 affected147 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0003 affected145 at risk EG0011 affected147 at risk
Hypoxia	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0001 affected145 at risk EG0011 affected147 at risk
Lung disorder	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0001 affected145 at risk EG0012 affected147 at risk
Lung infiltration	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0001 affected145 at risk EG0011 affected147 at risk
Pleural effusion	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0000 affected145 at risk EG0011 affected147 at risk
Pneumonitis	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0001 affected145 at risk EG0011 affected147 at risk
Pneumothorax	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0000 affected145 at risk EG0011 affected147 at risk
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0001 affected145 at risk EG0011 affected147 at risk
Pulmonary oedema	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0000 affected145 at risk EG0012 affected147 at risk
Respiratory distress	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0002 affected145 at risk EG0011 affected147 at risk
Respiratory failure	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0001 affected145 at risk EG0012 affected147 at risk
Anaemia	Blood and lymphatic system disorders	Systematic Assessment	EG0001 affected145 at risk EG0012 affected147 at risk
Bone marrow failure	Blood and lymphatic system disorders	Systematic Assessment	EG0001 affected145 at risk EG0010 affected147 at risk
Febrile bone marrow aplasia	Blood and lymphatic system disorders	Systematic Assessment	EG0004 affected145 at risk EG0013 affected147 at risk
Febrile neutropenia	Blood and lymphatic system disorders	Systematic Assessment	EG00041 affected145 at risk EG00133 affected147 at risk
Neutropenia	Blood and lymphatic system disorders	Systematic Assessment	EG0002 affected145 at risk EG0010 affected147 at risk
Thrombocytopenia	Blood and lymphatic system disorders	Systematic Assessment	EG0003 affected145 at risk EG0012 affected147 at risk
Brain stem infarction	Nervous system disorders	Systematic Assessment	EG0000 affected145 at risk EG0011 affected147 at risk
Cerebral haemorrhage	Nervous system disorders	Systematic Assessment	EG0001 affected145 at risk EG0011 affected147 at risk
Cerebral ischaemia	Nervous system disorders	Systematic Assessment	EG0000 affected145 at risk EG0012 affected147 at risk
Haemorrhage intracranial	Nervous system disorders	Systematic Assessment	EG0002 affected145 at risk EG0012 affected147 at risk
Hydrocephalus	Nervous system disorders	Systematic Assessment	EG0001 affected145 at risk EG0010 affected147 at risk
Peripheral motor neuropathy	Nervous system disorders	Systematic Assessment	EG0001 affected145 at risk EG0010 affected147 at risk
Peripheral sensory neuropathy	Nervous system disorders	Systematic Assessment	EG0001 affected145 at risk EG0010 affected147 at risk
Sciatica	Nervous system disorders	Systematic Assessment	EG0001 affected145 at risk EG0010 affected147 at risk
Deafness unilateral	Ear and labyrinth disorders	Systematic Assessment	EG0001 affected145 at risk EG0010 affected147 at risk
Colitis	Gastrointestinal disorders	Systematic Assessment	EG0001 affected145 at risk EG0010 affected147 at risk
Constipation	Gastrointestinal disorders	Systematic Assessment	EG0001 affected145 at risk EG0010 affected147 at risk
Diarrhoea	Gastrointestinal disorders	Systematic Assessment	EG0001 affected145 at risk EG0010 affected147 at risk
Haemorrhoids	Gastrointestinal disorders	Systematic Assessment	EG0001 affected145 at risk EG0010 affected147 at risk
Ileus	Gastrointestinal disorders	Systematic Assessment	EG0000 affected145 at risk EG0011 affected147 at risk
Large intestine perforation	Gastrointestinal disorders	Systematic Assessment	EG0000 affected145 at risk EG0011 affected147 at risk
Lower gastrointestinal haemorrhage	Gastrointestinal disorders	Systematic Assessment	EG0002 affected145 at risk EG0010 affected147 at risk
Mouth haemorrhage	Gastrointestinal disorders	Systematic Assessment	EG0001 affected145 at risk EG0010 affected147 at risk
Neutropenic colitis	Gastrointestinal disorders	Systematic Assessment	EG0001 affected145 at risk EG0010 affected147 at risk
Oesophageal mucosal tear	Gastrointestinal disorders	Systematic Assessment	EG0001 affected145 at risk EG0010 affected147 at risk
Oesophagitis	Gastrointestinal disorders	Systematic Assessment	EG0000 affected145 at risk EG0011 affected147 at risk
Oral mucosal erythema	Gastrointestinal disorders	Systematic Assessment	EG0000 affected145 at risk EG0011 affected147 at risk
Rectal haemorrhage	Gastrointestinal disorders	Systematic Assessment	EG0001 affected145 at risk EG0010 affected147 at risk
Salivary gland enlargement	Gastrointestinal disorders	Systematic Assessment	EG0000 affected145 at risk EG0011 affected147 at risk
Stomatitis	Gastrointestinal disorders	Systematic Assessment	EG0002 affected145 at risk EG0011 affected147 at risk
Tongue oedema	Gastrointestinal disorders	Systematic Assessment	EG0000 affected145 at risk EG0011 affected147 at risk
Upper gastrointestinal haemorrhage	Gastrointestinal disorders	Systematic Assessment	EG0001 affected145 at risk EG0010 affected147 at risk
Acute kidney injury	Renal and urinary disorders	Systematic Assessment	EG0000 affected145 at risk EG0012 affected147 at risk
Haematuria	Renal and urinary disorders	Systematic Assessment	EG0001 affected145 at risk EG0010 affected147 at risk
Renal colic	Renal and urinary disorders	Systematic Assessment	EG0000 affected145 at risk EG0011 affected147 at risk
Renal failure	Renal and urinary disorders	Systematic Assessment	EG0002 affected145 at risk EG0010 affected147 at risk
Cholecystitis	Hepatobiliary disorders	Systematic Assessment	EG0001 affected145 at risk EG0011 affected147 at risk
Drug reaction with eosinophilia and systemic symptoms	Skin and subcutaneous tissue disorders	Systematic Assessment	EG0001 affected145 at risk EG0010 affected147 at risk
Skin ulcer	Skin and subcutaneous tissue disorders	Systematic Assessment	EG0000 affected145 at risk EG0011 affected147 at risk
Arthritis	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG0001 affected145 at risk EG0010 affected147 at risk
Rotator cuff syndrome	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG0001 affected145 at risk EG0010 affected147 at risk
Hypercalcaemia	Metabolism and nutrition disorders	Systematic Assessment	EG0000 affected145 at risk EG0011 affected147 at risk
Abdominal infection	Infections and infestations	Systematic Assessment	EG0000 affected145 at risk EG0011 affected147 at risk
Anal abscess	Infections and infestations	Systematic Assessment	EG0002 affected145 at risk EG0012 affected147 at risk
Anal infection	Infections and infestations	Systematic Assessment	EG0001 affected145 at risk EG0011 affected147 at risk
Anorectal infection	Infections and infestations	Systematic Assessment	EG0001 affected145 at risk EG0010 affected147 at risk
Arthritis bacterial	Infections and infestations	Systematic Assessment	EG0001 affected145 at risk EG0010 affected147 at risk
Aspergillus infection	Infections and infestations	Systematic Assessment	EG0001 affected145 at risk EG0011 affected147 at risk
Bacteraemia	Infections and infestations	Systematic Assessment	EG0004 affected145 at risk EG0015 affected147 at risk
Bartholinitis	Infections and infestations	Systematic Assessment	EG0001 affected145 at risk EG0010 affected147 at risk
Bronchopulmonary aspergillosis	Infections and infestations	Systematic Assessment	EG0004 affected145 at risk EG0010 affected147 at risk
Cellulitis	Infections and infestations	Systematic Assessment	EG0004 affected145 at risk EG0012 affected147 at risk
Clostridium difficile colitis	Infections and infestations	Systematic Assessment	EG0002 affected145 at risk EG0010 affected147 at risk
Corynebacterium bacteraemia	Infections and infestations	Systematic Assessment	EG0000 affected145 at risk EG0011 affected147 at risk
Cystitis	Infections and infestations	Systematic Assessment	EG0001 affected145 at risk EG0010 affected147 at risk
Cytomegalovirus viraemia	Infections and infestations	Systematic Assessment	EG0000 affected145 at risk EG0011 affected147 at risk
Dermo-hypodermitis	Infections and infestations	Systematic Assessment	EG0001 affected145 at risk EG0010 affected147 at risk
Device related infection	Infections and infestations	Systematic Assessment	EG0004 affected145 at risk EG0013 affected147 at risk
Disseminated varicella zoster vaccine virus infection	Infections and infestations	Systematic Assessment	EG0001 affected145 at risk EG0010 affected147 at risk
Diverticulitis	Infections and infestations	Systematic Assessment	EG0001 affected145 at risk EG0010 affected147 at risk
Ecthyma	Infections and infestations	Systematic Assessment	EG0001 affected145 at risk EG0010 affected147 at risk
Endocarditis	Infections and infestations	Systematic Assessment	EG0001 affected145 at risk EG0010 affected147 at risk
Enteritis infectious	Infections and infestations	Systematic Assessment	EG0001 affected145 at risk EG0010 affected147 at risk
Enterobacter infection	Infections and infestations	Systematic Assessment	EG0000 affected145 at risk EG0011 affected147 at risk
Enterococcal bacteraemia	Infections and infestations	Systematic Assessment	EG0001 affected145 at risk EG0010 affected147 at risk
External ear cellulitis	Infections and infestations	Systematic Assessment	EG0000 affected145 at risk EG0011 affected147 at risk
Fungal infection	Infections and infestations	Systematic Assessment	EG0001 affected145 at risk EG0010 affected147 at risk
Gastroenteritis	Infections and infestations	Systematic Assessment	EG0000 affected145 at risk EG0011 affected147 at risk
Genital infection	Infections and infestations	Systematic Assessment	EG0000 affected145 at risk EG0011 affected147 at risk
Groin abscess	Infections and infestations	Systematic Assessment	EG0001 affected145 at risk EG0010 affected147 at risk
Herpes simplex	Infections and infestations	Systematic Assessment	EG0001 affected145 at risk EG0010 affected147 at risk
Infective myositis	Infections and infestations	Systematic Assessment	EG0000 affected145 at risk EG0011 affected147 at risk
Influenza	Infections and infestations	Systematic Assessment	EG0000 affected145 at risk EG0011 affected147 at risk
Intestinal sepsis	Infections and infestations	Systematic Assessment	EG0001 affected145 at risk EG0010 affected147 at risk
Klebsiella bacteraemia	Infections and infestations	Systematic Assessment	EG0001 affected145 at risk EG0011 affected147 at risk
Liver abscess	Infections and infestations	Systematic Assessment	EG0001 affected145 at risk EG0010 affected147 at risk
Mucormycosis	Infections and infestations	Systematic Assessment	EG0001 affected145 at risk EG0010 affected147 at risk
Necrotising fasciitis	Infections and infestations	Systematic Assessment	EG0000 affected145 at risk EG0011 affected147 at risk
Neutropenic infection	Infections and infestations	Systematic Assessment	EG0001 affected145 at risk EG0010 affected147 at risk
Oral infection	Infections and infestations	Systematic Assessment	EG0001 affected145 at risk EG0010 affected147 at risk
Otitis media	Infections and infestations	Systematic Assessment	EG0000 affected145 at risk EG0011 affected147 at risk
Parvovirus B19 infection	Infections and infestations	Systematic Assessment	EG0001 affected145 at risk EG0010 affected147 at risk
Perineal abscess	Infections and infestations	Systematic Assessment	EG0000 affected145 at risk EG0011 affected147 at risk
Periorbital cellulitis	Infections and infestations	Systematic Assessment	EG0001 affected145 at risk EG0010 affected147 at risk
Pharyngitis	Infections and infestations	Systematic Assessment	EG0001 affected145 at risk EG0010 affected147 at risk
Pneumocystis jirovecii pneumonia	Infections and infestations	Systematic Assessment	EG0002 affected145 at risk EG0010 affected147 at risk
Pneumonia	Infections and infestations	Systematic Assessment	EG00027 affected145 at risk EG00125 affected147 at risk
Pseudomonal bacteraemia	Infections and infestations	Systematic Assessment	EG0001 affected145 at risk EG0010 affected147 at risk
Respiratory tract infection	Infections and infestations	Systematic Assessment	EG0002 affected145 at risk EG0010 affected147 at risk
Respiratory tract infection viral	Infections and infestations	Systematic Assessment	EG0000 affected145 at risk EG0011 affected147 at risk
Sepsis	Infections and infestations	Systematic Assessment	EG00015 affected145 at risk EG00116 affected147 at risk
Septic shock	Infections and infestations	Systematic Assessment	EG0007 affected145 at risk EG0015 affected147 at risk
Sinusitis fungal	Infections and infestations	Systematic Assessment	EG0001 affected145 at risk EG0010 affected147 at risk
Soft tissue infection	Infections and infestations	Systematic Assessment	EG0000 affected145 at risk EG0013 affected147 at risk
Staphylococcal bacteraemia	Infections and infestations	Systematic Assessment	EG0001 affected145 at risk EG0012 affected147 at risk
Staphylococcal sepsis	Infections and infestations	Systematic Assessment	EG0001 affected145 at risk EG0010 affected147 at risk
Streptococcal bacteraemia	Infections and infestations	Systematic Assessment	EG0002 affected145 at risk EG0012 affected147 at risk
Streptococcal sepsis	Infections and infestations	Systematic Assessment	EG0000 affected145 at risk EG0011 affected147 at risk
Subcutaneous abscess	Infections and infestations	Systematic Assessment	EG0001 affected145 at risk EG0010 affected147 at risk
Tooth abscess	Infections and infestations	Systematic Assessment	EG0001 affected145 at risk EG0010 affected147 at risk
Upper respiratory tract infection	Infections and infestations	Systematic Assessment	EG0000 affected145 at risk EG0011 affected147 at risk
Urinary tract infection	Infections and infestations	Systematic Assessment	EG0002 affected145 at risk EG0011 affected147 at risk
Urosepsis	Infections and infestations	Systematic Assessment	EG0001 affected145 at risk EG0010 affected147 at risk
Escherichia bacteraemia	Infections and infestations	Systematic Assessment	EG0001 affected145 at risk EG0012 affected147 at risk

Other Adverse Events

Term	Organ System	Assessment Type	Statistical Information
Hypertension	Vascular disorders	Systematic Assessment	EG00015 affected145 at risk EG0014 affected147 at risk
Hypotension	Vascular disorders	Systematic Assessment	EG00019 affected145 at risk EG00111 affected147 at risk
Asthenia	General disorders	Systematic Assessment	EG00011 affected145 at risk EG00115 affected147 at risk
Fatigue	General disorders	Systematic Assessment	EG00020 affected145 at risk EG00127 affected147 at risk
Injection site reaction	General disorders	Systematic Assessment	EG00029 affected145 at risk EG00112 affected147 at risk
Oedema peripheral	General disorders	Systematic Assessment	EG00023 affected145 at risk EG00123 affected147 at risk
Pyrexia	General disorders	Systematic Assessment	EG00033 affected145 at risk EG00136 affected147 at risk
Insomnia	Psychiatric disorders	Systematic Assessment	EG00014 affected145 at risk EG00113 affected147 at risk
Contusion	Injury, poisoning and procedural complications	Systematic Assessment	EG00011 affected145 at risk EG0016 affected147 at risk
Alanine aminotransferase increased	Investigations	Systematic Assessment	EG00012 affected145 at risk EG0017 affected147 at risk
Aspartate aminotransferase increased	Investigations	Systematic Assessment	EG00011 affected145 at risk EG0018 affected147 at risk
Blood alkaline phosphatase increased	Investigations	Systematic Assessment	EG0006 affected145 at risk EG0018 affected147 at risk
Blood bilirubin increased	Investigations	Systematic Assessment	EG0008 affected145 at risk EG0019 affected147 at risk
Blood creatinine increased	Investigations	Systematic Assessment	EG0008 affected145 at risk EG0014 affected147 at risk
Weight decreased	Investigations	Systematic Assessment	EG0005 affected145 at risk EG0019 affected147 at risk
Anaemia	Blood and lymphatic system disorders	Systematic Assessment	EG00037 affected145 at risk EG00141 affected147 at risk
Febrile neutropenia	Blood and lymphatic system disorders	Systematic Assessment	EG00025 affected145 at risk EG00129 affected147 at risk
Leukopenia	Blood and lymphatic system disorders	Systematic Assessment	EG00014 affected145 at risk EG00114 affected147 at risk
Neutropenia	Blood and lymphatic system disorders	Systematic Assessment	EG00047 affected145 at risk EG00128 affected147 at risk
Thrombocytopenia	Blood and lymphatic system disorders	Systematic Assessment	EG00043 affected145 at risk EG00146 affected147 at risk
Cough	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG00022 affected145 at risk EG00127 affected147 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG00020 affected145 at risk EG00117 affected147 at risk
Epistaxis	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG00016 affected145 at risk EG00116 affected147 at risk
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0004 affected145 at risk EG0019 affected147 at risk
Dizziness	Nervous system disorders	Systematic Assessment	EG0008 affected145 at risk EG00111 affected147 at risk
Headache	Nervous system disorders	Systematic Assessment	EG00030 affected145 at risk EG00120 affected147 at risk
Abdominal pain	Gastrointestinal disorders	Systematic Assessment	EG00011 affected145 at risk EG00111 affected147 at risk
Constipation	Gastrointestinal disorders	Systematic Assessment	EG00033 affected145 at risk EG00133 affected147 at risk
Diarrhoea	Gastrointestinal disorders	Systematic Assessment	EG00036 affected145 at risk EG00132 affected147 at risk
Dyspepsia	Gastrointestinal disorders	Systematic Assessment	EG00012 affected145 at risk EG0015 affected147 at risk
Haemorrhoids	Gastrointestinal disorders	Systematic Assessment	EG00011 affected145 at risk EG0019 affected147 at risk
Nausea	Gastrointestinal disorders	Systematic Assessment	EG00042 affected145 at risk EG00138 affected147 at risk
Stomatitis	Gastrointestinal disorders	Systematic Assessment	EG00016 affected145 at risk EG00120 affected147 at risk
Vomiting	Gastrointestinal disorders	Systematic Assessment	EG00024 affected145 at risk EG00120 affected147 at risk
Dysuria	Renal and urinary disorders	Systematic Assessment	EG0008 affected145 at risk EG0012 affected147 at risk
Petechiae	Skin and subcutaneous tissue disorders	Systematic Assessment	EG00012 affected145 at risk EG0017 affected147 at risk
Rash	Skin and subcutaneous tissue disorders	Systematic Assessment	EG00011 affected145 at risk EG0019 affected147 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG00012 affected145 at risk EG00110 affected147 at risk
Back pain	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG00015 affected145 at risk EG00112 affected147 at risk
Myalgia	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG0008 affected145 at risk EG0015 affected147 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG00011 affected145 at risk EG0017 affected147 at risk
Decreased appetite	Metabolism and nutrition disorders	Systematic Assessment	EG00027 affected145 at risk EG00120 affected147 at risk
Hyperkalaemia	Metabolism and nutrition disorders	Systematic Assessment	EG0009 affected145 at risk EG0013 affected147 at risk
Hypoalbuminaemia	Metabolism and nutrition disorders	Systematic Assessment	EG00010 affected145 at risk EG0017 affected147 at risk
Hypocalcaemia	Metabolism and nutrition disorders	Systematic Assessment	EG0009 affected145 at risk EG0015 affected147 at risk
Hypokalaemia	Metabolism and nutrition disorders	Systematic Assessment	EG00029 affected145 at risk EG00138 affected147 at risk
Hypomagnesaemia	Metabolism and nutrition disorders	Systematic Assessment	EG00014 affected145 at risk EG00116 affected147 at risk
Hyponatraemia	Metabolism and nutrition disorders	Systematic Assessment	EG00010 affected145 at risk EG0013 affected147 at risk
Hypophosphataemia	Metabolism and nutrition disorders	Systematic Assessment	EG00013 affected145 at risk EG0019 affected147 at risk
Oral herpes	Infections and infestations	Systematic Assessment	EG0008 affected145 at risk EG0015 affected147 at risk
Pneumonia	Infections and infestations	Systematic Assessment	EG00015 affected145 at risk EG00114 affected147 at risk

ID	Term
D007951	Leukemia, Myeloid
D007938	Leukemia
D009370	Neoplasms by Histologic Type
D009369	Neoplasms
D006402	Hematologic Diseases
D006425	Hemic and Lymphatic Diseases