Study of MLN4924 Plus Azacitidine in Treatment-naive Part... | NCT01814826

ID	Type	Description	Link
U1111-1221-2792	Other Identifier	WHO

Label	Type	Description	Intervention Names
MLN4924 and Azacitidine	Experimental		Drug: MLN4924 Drug: Azacitidine

Name	Type	Description	Arm Group Labels	Other Names
MLN4924	Drug	MLN4924 intravenously (IV) in AML participants in a 28-day cycle: MLN4924 on Days 1, 3, and 5 for Cycle 1 and all subsequent cycles	MLN4924 and Azacitidine

Measure	Description	Time Frame
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)		Baseline up to 30 days after the last dose of study drug (up to 5 years)
Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings		Baseline up to 30 days after the last dose of study drug (up to 5 years)
Number of Participants With TEAEs Related to Clinically Significant Vital Sign Findings		Baseline up to 30 days after the last dose of study drug (up to 5 years)

Measure	Description	Time Frame
Dose-escalation Phase, Cmax: Maximum Observed Plasma Concentration for MLN4924		Cycle 1 Day 1 pre-dose and at multiple time points (up to 24 hours) post-dose; Cycle 1 Day 5 pre-dose and at multiple time points (up to 48 hours) post-dose (Cycle length is equal to [=] 28 days)
Maximum Tolerated Dose (MTD) Expansion Phase, Cmax: Maximum Observed Plasma Concentration for MLN4924

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Participants with world health organization (WHO)-defined AML, 60 years of age or older, who are unlikely to benefit from standard induction therapy, defined as having at least 1 of the following:
- Greater than or equal to 75 years of age.
- Antecedent hematologic disease.
- Known adverse cytogenetic risk.
- Eastern Cooperative Oncology Group (ECOG) PS = 2.
- Participant must not have received definitive treatment for AML, defined as any prior chemotherapy with antileukemic activity.
ECOG PS 0 to 2.
Expected survival longer than 3 months from enrollment in the study.
Female participants who are post menopausal, surgically sterile, or agree to practice 2 effective methods of contraception or agree to practice true abstinence.
Male participants who agree to practice effective barrier contraception or agree to practice true abstinence.
Voluntary written consent must be given before performance of any study-related procedure.
Suitable venous access for the study-required blood sampling.
Clinical laboratory values as specified below within 3 days before the first dose of any study drug:

•Total bilirubin must be less than or equal to (<=) the upper limit of the normal range (ULN).
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) must be<=2.5*ULN.
- Serum creatinine <=1.5*ULN.
- Albumin greater than or equal to (>=) 27 grams per liter (g/L).
- Hemoglobin >9 grams per deciliter (g/dL). Note: It was permissible to transfuse participants with red blood cells to achieve this criterion.
- White blood cell (WBC) count less than (<) 50,000 per microliter (/mcL) before administration of pevonedistat on Days 1, 3, and 5 of Cycle 1.
Note: Hydroxyurea could be used to control the level of circulating leukemic blast cell counts to no lower than 10,000/mcL while on pevonedistat.
Able to undergo bone marrow aspiration and biopsy at screening.

Exclusion Criteria:

Previous treatment with azacitidine or decitabine.
Known favorable cytogenetic risk.
Any serious medical or psychiatric illness.
Treatment with any investigational products.
Known hypersensitivity to azacitidine or mannitol.
Acute promyelocytic leukemia as diagnosed by morphologic examination of bone marrow, by fluorescent in situ hybridization or cytogenetics of peripheral blood or bone marrow, or by other accepted analysis.
Active uncontrolled infection or severe infectious disease.
Major surgery within 14 days before the first dose of study drug.
Life-threatening illness unrelated to cancer.
Clinically uncontrolled central nervous system (CNS) involvement.
WBC count greater than (>) 50,000/ mcL.
Prothrombin time (PT) or activated partial thromboplastin time (aPTT) >1.5* ULN or a history of coagulopathy or bleeding disorder
Known human immunodeficiency virus (HIV) positive.
Known hepatitis B surface antigen-positive, or known or suspected active hepatitis C infection
Known hepatic cirrhosis or severe pre-existing hepatic impairment.
Known cardiac/cardiopulmonary disease defined as 1 of the following:
- Uncontrolled high blood pressure (that is, systolic blood pressure >180 milliliter per mercury (mm Hg), diastolic blood pressure >95 mm Hg).
- Congestive heart failure New York Heart Association (NYHA) Class III or IV, or Class II with a recent decompensation that required hospitalization or referral to a heart failure clinic within 4 weeks before screening (see Section 15.4 of the protocol in Appendix 16.1.1).
- Cardiomyopathy or history of ischemic heart disease
- Participants with ischemic heart disease who had acute coronary syndrome (ACS), myocardial infarction (MI), and/or revascularization (example, coronary artery bypass graft, stent) in the past 6 months were excluded. However, participants with ischemic heart disease who had ACS, MI, and/or revascularization greater than 6 months before screening and who are without cardiac symptoms could be enrolled.
- Arrhythmia (example, history of polymorphic ventricular fibrillation or torsade de pointes). However, participants with <Grade 3 atrial fibrillation (a fib) for a period of at least 6 months could enroll. Grade 3 a fib is symptomatic and incompletely controlled medically, or controlled with device (example, pacemaker), or ablation. Participants with paroxysmal a fib were permitted to enroll.
- Implantable cardioverter defibrillator.
- Moderate to severe aortic and/or mitral stenosis or other valvulopathy (ongoing).
- Pulmonary arterial hypertension. Prolonged rate corrected QT (QTc) interval >= 500 msec, calculated according to institutional guidelines
Left ventricular ejection fraction
Known moderate to severe chronic obstructive pulmonary disease, interstitial lung disease, and pulmonary fibrosis.
Body mass index >40 kilogram per square meter (kg/m^2).
Treatment with CYP3A inducers within 14 days before the first dose of MLN4924.
Systemic antineoplastic therapy or radiotherapy within 14 days before the first dose of study drug, except for hydroxyurea.

Name	Affiliation	Role
Medical Monitor	Millennium Pharmaceuticals, Inc.	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
University of Alabama at Birmingham		Birmingham	Alabama	35294	United States
Stanford University

PubMed Identifier	Type	Citation	Retractions
29348128	Result	Swords RT, Coutre S, Maris MB, Zeidner JF, Foran JM, Cruz J, Erba HP, Berdeja JG, Tam W, Vardhanabhuti S, Pawlikowska-Dobler I, Faessel HM, Dash AB, Sedarati F, Dezube BJ, Faller DV, Savona MR. Pevonedistat, a first-in-class NEDD8-activating enzyme inhibitor, combined with azacitidine in patients with AML. Blood. 2018 Mar 29;131(13):1415-1424. doi: 10.1182/blood-2017-09-805895. Epub 2018 Jan 18.
31355467

ID	Title	Description
FG000	MLN4924 20 mg/m^2 + Azacitidine 75 mg/m^2 Intravenous	MLN4924 20 mg/m^2, infusion, intravenously, once on Days 1, 3, and 5 in combination with azacitidine 75 mg/m^2, infusion, intravenously, once on Days 1 through 5, 8 and 9 before administration of MLN4924 in a 28-day treatment cycle up to symptomatic deterioration or progressive disease (PD), or until treatment was discontinued for another reason (up to Cycle 53).

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

Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

The safety population was defined as all enrolled participants who receive at least 1 dose of any study drug, MLN4924 or azacitidine.

Posted

Count of Participants

Participants

Baseline up to 30 days after the last dose of study drug (up to 5 years)

ID	Title	Description
OG000	MLN4924 20 mg/m^2 + Azacitidine 75 mg/m^2 Intravenous	MLN4924 20 mg/m^2, infusion, intravenously, once on Days 1, 3, and 5 in combination with azacitidine 75 mg/m^2, infusion, intravenously, once on Days 1 through 5, 8 and 9 before administration of MLN4924 in a 28-day treatment cycle up to symptomatic deterioration or progressive disease (PD), or until treatment was discontinued for another reason (up to Cycle 53).
OG001	MLN4924 20 mg/m^2 + Azacitidine 75 mg/m^2 Subcutaneous	MLN4924 20 mg/m^2, infusion, intravenously, once on Days 1, 3, and 5 in combination with azacitidine 75 mg/m^2, infusion, subcutaneously, once on Days 1 through 5, 8 and 9 before administration of MLN4924 in a 28-day treatment cycle up to symptomatic deterioration or PD, or until treatment was discontinued for another reason (up to Cycle 53).
OG002	MLN4924 30 mg/m^2 + Azacitidine 75 mg/m^2 Intravenous	MLN4924 30 mg/m^2, infusion, intravenously, once on Days 1, 3, and 5 in combination with azacitidine 75 mg/m^2, infusion, intravenously, once on Days 1 through 5, 8 and 9 before administration of MLN4924 in a 28-day treatment cycle up to symptomatic deterioration or PD, or until treatment was discontinued for another reason (up to Cycle 53).

Units	Counts
Participants	OG00032 OG00129 OG0023

Title

Denominators

Categories

TEAEs

Title	Measurements
	OG00032 OG00129 OG0023

SAEs

Primary

Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings

The safety population was defined as all enrolled participants who receive at least 1 dose of any study drug, MLN4924 or azacitidine.

Posted

Count of Participants

Participants

Baseline up to 30 days after the last dose of study drug (up to 5 years)

ID	Title	Description
OG000	MLN4924 20 mg/m^2 + Azacitidine 75 mg/m^2 Intravenous	MLN4924 20 mg/m^2, infusion, intravenously, once on Days 1, 3, and 5 in combination with azacitidine 75 mg/m^2, infusion, intravenously, once on Days 1 through 5, 8 and 9 before administration of MLN4924 in a 28-day treatment cycle up to symptomatic deterioration or progressive disease (PD), or until treatment was discontinued for another reason (up to Cycle 53).
OG001	MLN4924 20 mg/m^2 + Azacitidine 75 mg/m^2 Subcutaneous	MLN4924 20 mg/m^2, infusion, intravenously, once on Days 1, 3, and 5 in combination with azacitidine 75 mg/m^2, infusion, subcutaneously, once on Days 1 through 5, 8 and 9 before administration of MLN4924 in a 28-day treatment cycle up to symptomatic deterioration or PD, or until treatment was discontinued for another reason (up to Cycle 53).
OG002	MLN4924 30 mg/m^2 + Azacitidine 75 mg/m^2 Intravenous

Primary

Number of Participants With TEAEs Related to Clinically Significant Vital Sign Findings

The safety population was defined as all enrolled participants who receive at least 1 dose of any study drug, MLN4924 or azacitidine.

Posted

Count of Participants

Participants

Baseline up to 30 days after the last dose of study drug (up to 5 years)

ID	Title	Description
OG000	MLN4924 20 mg/m^2 + Azacitidine 75 mg/m^2 Intravenous	MLN4924 20 mg/m^2, infusion, intravenously, once on Days 1, 3, and 5 in combination with azacitidine 75 mg/m^2, infusion, intravenously, once on Days 1 through 5, 8 and 9 before administration of MLN4924 in a 28-day treatment cycle up to symptomatic deterioration or progressive disease (PD), or until treatment was discontinued for another reason (up to Cycle 53).
OG001	MLN4924 20 mg/m^2 + Azacitidine 75 mg/m^2 Subcutaneous	MLN4924 20 mg/m^2, infusion, intravenously, once on Days 1, 3, and 5 in combination with azacitidine 75 mg/m^2, infusion, subcutaneously, once on Days 1 through 5, 8 and 9 before administration of MLN4924 in a 28-day treatment cycle up to symptomatic deterioration or PD, or until treatment was discontinued for another reason (up to Cycle 53).
OG002	MLN4924 30 mg/m^2 + Azacitidine 75 mg/m^2 Intravenous

Secondary

Dose-escalation Phase, Cmax: Maximum Observed Plasma Concentration for MLN4924

The pharmacokinetic (PK)-evaluable population was defined as all enrolled participants who had sufficient dosing in Cycle 1 and MLN4924 concentration-time data to reliably estimate PK parameters. The PK population where data at specified time points was available.

Posted

Mean

Standard Deviation

nanogram per milliliter (ng/mL)

Cycle 1 Day 1 pre-dose and at multiple time points (up to 24 hours) post-dose; Cycle 1 Day 5 pre-dose and at multiple time points (up to 48 hours) post-dose (Cycle length is equal to [=] 28 days)

ID	Title	Description
OG000	MLN4924 20 mg/m^2 + Azacitidine 75 mg/m^2 Intravenous	MLN4924 20 mg/m^2, infusion, intravenously, once on Days 1, 3, and 5 in combination with azacitidine 75 mg/m^2, infusion, intravenously, once on Days 1 through 5, 8 and 9 before administration of MLN4924 in a 28-day treatment cycle up to symptomatic deterioration or progressive disease (PD), or until treatment was discontinued for another reason (up to Cycle 53).
OG001	MLN4924 30 mg/m^2 + Azacitidine 75 mg/m^2 Intravenous	MLN4924 30 mg/m^2, infusion, intravenously, once on Days 1, 3, and 5 in combination with azacitidine 75 mg/m^2, infusion, intravenously, once on Days 1 through 5, 8 and 9 before administration of MLN4924 in a 28-day treatment cycle up to symptomatic deterioration or PD, or until treatment was discontinued for another reason (up to Cycle 53).

Secondary

Maximum Tolerated Dose (MTD) Expansion Phase, Cmax: Maximum Observed Plasma Concentration for MLN4924

The PK-evaluable population was defined as all enrolled participants who had sufficient dosing in Cycle 1 and MLN4924 concentration-time data to reliably estimate PK parameters. The PK population where data at specified time points was available.

Posted

Mean

Standard Deviation

ng/mL

Cycle 1 Day 1 pre-dose and at multiple time points (up to 24 hours) post-dose; Cycle 1 Day 5 pre-dose and at multiple time points (up to 48 hours) post-dose (Cycle length = 28 days)

ID	Title	Description
OG000	MLN4924 20 mg/m^2 + Azacitidine 75 mg/m^2 Intravenous	MLN4924 20 mg/m^2, infusion, intravenously, once on Days 1, 3, and 5 in combination with azacitidine 75 mg/m^2, infusion, intravenously, once on Days 1 through 5, 8 and 9 before administration of MLN4924 in a 28-day treatment cycle up to symptomatic deterioration or progressive disease (PD), or until treatment was discontinued for another reason (up to Cycle 53).
OG001	MLN4924 20 mg/m^2 + Azacitidine 75 mg/m^2 Subcutaneous	MLN4924 20 mg/m^2, infusion, intravenously, once on Days 1, 3, and 5 in combination with azacitidine 75 mg/m^2, infusion, subcutaneously, once on Days 1 through 5, 8 and 9 before administration of MLN4924 in a 28-day treatment cycle up to symptomatic deterioration or PD, or until treatment was discontinued for another reason (up to Cycle 53).

Secondary

Dose-escalation Phase, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for MLN4924

Posted

Median

Full Range

hour

Cycle 1 Day 1 pre-dose and at multiple time points (up to 24 hours) post-dose; Cycle 1 Day 5 pre-dose and at multiple time points (up to 48 hours) post-dose (Cycle length = 28 days)

ID	Title	Description
OG000	MLN4924 20 mg/m^2 + Azacitidine 75 mg/m^2 Intravenous	MLN4924 20 mg/m^2, infusion, intravenously, once on Days 1, 3, and 5 in combination with azacitidine 75 mg/m^2, infusion, intravenously, once on Days 1 through 5, 8 and 9 before administration of MLN4924 in a 28-day treatment cycle up to symptomatic deterioration or progressive disease (PD), or until treatment was discontinued for another reason (up to Cycle 53).
OG001	MLN4924 30 mg/m^2 + Azacitidine 75 mg/m^2 Intravenous	MLN4924 30 mg/m^2, infusion, intravenously, once on Days 1, 3, and 5 in combination with azacitidine 75 mg/m^2, infusion, intravenously, once on Days 1 through 5, 8 and 9 before administration of MLN4924 in a 28-day treatment cycle up to symptomatic deterioration or PD, or until treatment was discontinued for another reason (up to Cycle 53).

Secondary

MTD Expansion Phase, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for MLN4924

Posted

Median

Full Range

hour

Cycle 1 Day 1 pre-dose and at multiple time points (up to 24 hours) post-dose; Cycle 1 Day 5 pre-dose and at multiple time points (up to 48 hours) post-dose (Cycle length = 28 days)

ID	Title	Description
OG000	MLN4924 20 mg/m^2 + Azacitidine 75 mg/m^2 Intravenous	MLN4924 20 mg/m^2, infusion, intravenously, once on Days 1, 3, and 5 in combination with azacitidine 75 mg/m^2, infusion, intravenously, once on Days 1 through 5, 8 and 9 before administration of MLN4924 in a 28-day treatment cycle up to symptomatic deterioration or progressive disease (PD), or until treatment was discontinued for another reason (up to Cycle 53).
OG001	MLN4924 20 mg/m^2 + Azacitidine 75 mg/m^2 Subcutaneous	MLN4924 20 mg/m^2, infusion, intravenously, once on Days 1, 3, and 5 in combination with azacitidine 75 mg/m^2, infusion, subcutaneously, once on Days 1 through 5, 8 and 9 before administration of MLN4924 in a 28-day treatment cycle up to symptomatic deterioration or PD, or until treatment was discontinued for another reason (up to Cycle 53).

Secondary

Dose-escalation Phase, Ctrough: Observed Plasma Concentration at the End of the Dosing Interval for MLN4924

Posted

Mean

Standard Deviation

ng/mL

Cycle 1 Day 1 pre-dose and at multiple time points (up to 24 hours) post-dose; Cycle 1 Day 5 pre-dose and at multiple time points (up to 48 hours) post-dose (Cycle length = 28 days)

ID	Title	Description
OG000	MLN4924 20 mg/m^2 + Azacitidine 75 mg/m^2 Intravenous	MLN4924 20 mg/m^2, infusion, intravenously, once on Days 1, 3, and 5 in combination with azacitidine 75 mg/m^2, infusion, intravenously, once on Days 1 through 5, 8 and 9 before administration of MLN4924 in a 28-day treatment cycle up to symptomatic deterioration or progressive disease (PD), or until treatment was discontinued for another reason (up to Cycle 53).
OG001	MLN4924 30 mg/m^2 + Azacitidine 75 mg/m^2 Intravenous	MLN4924 30 mg/m^2, infusion, intravenously, once on Days 1, 3, and 5 in combination with azacitidine 75 mg/m^2, infusion, intravenously, once on Days 1 through 5, 8 and 9 before administration of MLN4924 in a 28-day treatment cycle up to symptomatic deterioration or PD, or until treatment was discontinued for another reason (up to Cycle 53).

Secondary

MTD Expansion Phase, Ctrough: Observed Plasma Concentration at the End of the Dosing Interval for MLN4924

Posted

Mean

Standard Deviation

ng/mL

Cycle 1 Day 1 pre-dose and at multiple time points (up to 24 hours) post-dose; Cycle 1 Day 5 pre-dose and at multiple time points (up to 48 hours) post-dose (Cycle length = 28 days)

ID	Title	Description
OG000	MLN4924 20 mg/m^2 + Azacitidine 75 mg/m^2 Intravenous	MLN4924 20 mg/m^2, infusion, intravenously, once on Days 1, 3, and 5 in combination with azacitidine 75 mg/m^2, infusion, intravenously, once on Days 1 through 5, 8 and 9 before administration of MLN4924 in a 28-day treatment cycle up to symptomatic deterioration or progressive disease (PD), or until treatment was discontinued for another reason (up to Cycle 53).
OG001	MLN4924 20 mg/m^2 + Azacitidine 75 mg/m^2 Subcutaneous	MLN4924 20 mg/m^2, infusion, intravenously, once on Days 1, 3, and 5 in combination with azacitidine 75 mg/m^2, infusion, subcutaneously, once on Days 1 through 5, 8 and 9 before administration of MLN4924 in a 28-day treatment cycle up to symptomatic deterioration or PD, or until treatment was discontinued for another reason (up to Cycle 53).

Secondary

Dose-escalation Phase, AUC0-tau: Area Under the Plasma Concentration-time Curve From Time Zero to the End of the Dosing Interval (Tau) for MLN4924

Posted

Mean

Standard Deviation

hour*nanogram per milliliter (hr*ng/mL)

Cycle 1 Day 1 pre-dose and at multiple time points (up to 24 hours) post-dose; Cycle 1 Day 5 pre-dose and at multiple time points (up to 48 hours) post-dose (Cycle length = 28 days)

ID	Title	Description
OG000	MLN4924 20 mg/m^2 + Azacitidine 75 mg/m^2 Intravenous	MLN4924 20 mg/m^2, infusion, intravenously, once on Days 1, 3, and 5 in combination with azacitidine 75 mg/m^2, infusion, intravenously, once on Days 1 through 5, 8 and 9 before administration of MLN4924 in a 28-day treatment cycle up to symptomatic deterioration or progressive disease (PD), or until treatment was discontinued for another reason (up to Cycle 53).
OG001	MLN4924 30 mg/m^2 + Azacitidine 75 mg/m^2 Intravenous	MLN4924 30 mg/m^2, infusion, intravenously, once on Days 1, 3, and 5 in combination with azacitidine 75 mg/m^2, infusion, intravenously, once on Days 1 through 5, 8 and 9 before administration of MLN4924 in a 28-day treatment cycle up to symptomatic deterioration or PD, or until treatment was discontinued for another reason (up to Cycle 53).

Secondary

MTD Expansion Phase, AUC0-tau: Area Under the Plasma Concentration-time Curve From Time Zero to the End of the Dosing Interval (Tau) for MLN4924

Posted

Mean

Standard Deviation

hr*ng/mL

Cycle 1 Day 1 pre-dose and at multiple time points (up to 24 hours) post-dose; Cycle 1 Day 5 pre-dose and at multiple time points (up to 48 hours) post-dose (Cycle length = 28 days)

ID	Title	Description
OG000	MLN4924 20 mg/m^2 + Azacitidine 75 mg/m^2 Intravenous	MLN4924 20 mg/m^2, infusion, intravenously, once on Days 1, 3, and 5 in combination with azacitidine 75 mg/m^2, infusion, intravenously, once on Days 1 through 5, 8 and 9 before administration of MLN4924 in a 28-day treatment cycle up to symptomatic deterioration or progressive disease (PD), or until treatment was discontinued for another reason (up to Cycle 53).
OG001	MLN4924 20 mg/m^2 + Azacitidine 75 mg/m^2 Subcutaneous	MLN4924 20 mg/m^2, infusion, intravenously, once on Days 1, 3, and 5 in combination with azacitidine 75 mg/m^2, infusion, subcutaneously, once on Days 1 through 5, 8 and 9 before administration of MLN4924 in a 28-day treatment cycle up to symptomatic deterioration or PD, or until treatment was discontinued for another reason (up to Cycle 53).

Secondary

Dose-escalation Phase, AUC24hours: Area Under the Plasma Concentration-time Curve From Time Zero to 24 Hours Post-Dose for MLN4924

Posted

Mean

Standard Deviation

hr*ng/mL

Cycle 1 Day 1 pre-dose and at multiple time points (up to 24 hours) post-dose; Cycle 1 Day 5 pre-dose and at multiple time points (up to 24 hours) post-dose (Cycle length = 28 days)

ID	Title	Description
OG000	MLN4924 20 mg/m^2 + Azacitidine 75 mg/m^2 Intravenous	MLN4924 20 mg/m^2, infusion, intravenously, once on Days 1, 3, and 5 in combination with azacitidine 75 mg/m^2, infusion, intravenously, once on Days 1 through 5, 8 and 9 before administration of MLN4924 in a 28-day treatment cycle up to symptomatic deterioration or progressive disease (PD), or until treatment was discontinued for another reason (up to Cycle 53).
OG001	MLN4924 30 mg/m^2 + Azacitidine 75 mg/m^2 Intravenous	MLN4924 30 mg/m^2, infusion, intravenously, once on Days 1, 3, and 5 in combination with azacitidine 75 mg/m^2, infusion, intravenously, once on Days 1 through 5, 8 and 9 before administration of MLN4924 in a 28-day treatment cycle up to symptomatic deterioration or PD, or until treatment was discontinued for another reason (up to Cycle 53).

Secondary

MTD Expansion Phase, AUC24hours: Area Under the Plasma Concentration-time Curve From Time Zero to 24 Hours Post-Dose for MLN4924

Posted

Mean

Standard Deviation

hr*ng/mL

Cycle 1 Day 1 pre-dose and at multiple time points (up to 24 hours) post-dose; Cycle 1 Day 5 pre-dose and at multiple time points (up to 24 hours) post-dose (Cycle length = 28 days)

ID	Title	Description
OG000	MLN4924 20 mg/m^2 + Azacitidine 75 mg/m^2 Intravenous	MLN4924 20 mg/m^2, infusion, intravenously, once on Days 1, 3, and 5 in combination with azacitidine 75 mg/m^2, infusion, intravenously, once on Days 1 through 5, 8 and 9 before administration of MLN4924 in a 28-day treatment cycle up to symptomatic deterioration or progressive disease (PD), or until treatment was discontinued for another reason (up to Cycle 53).
OG001	MLN4924 20 mg/m^2 + Azacitidine 75 mg/m^2 Subcutaneous	MLN4924 20 mg/m^2, infusion, intravenously, once on Days 1, 3, and 5 in combination with azacitidine 75 mg/m^2, infusion, subcutaneously, once on Days 1 through 5, 8 and 9 before administration of MLN4924 in a 28-day treatment cycle up to symptomatic deterioration or PD, or until treatment was discontinued for another reason (up to Cycle 53).

Secondary

Dose-escalation Phase, AUCinf: Area Under the Plasma Concentration-time Curve Extrapolated to Infinity for MLN4924

Posted

Mean

Standard Deviation

hr*ng/mL

Cycle 1 Day 1 pre-dose and at multiple time points (up to 24 hours) post-dose; Cycle 1 Day 5 pre-dose and at multiple time points (up to 48 hours) post-dose (Cycle length = 28 days)

ID	Title	Description
OG000	MLN4924 20 mg/m^2 + Azacitidine 75 mg/m^2 Intravenous	MLN4924 20 mg/m^2, infusion, intravenously, once on Days 1, 3, and 5 in combination with azacitidine 75 mg/m^2, infusion, intravenously, once on Days 1 through 5, 8 and 9 before administration of MLN4924 in a 28-day treatment cycle up to symptomatic deterioration or progressive disease (PD), or until treatment was discontinued for another reason (up to Cycle 53).
OG001	MLN4924 30 mg/m^2 + Azacitidine 75 mg/m^2 Intravenous	MLN4924 30 mg/m^2, infusion, intravenously, once on Days 1, 3, and 5 in combination with azacitidine 75 mg/m^2, infusion, intravenously, once on Days 1 through 5, 8 and 9 before administration of MLN4924 in a 28-day treatment cycle up to symptomatic deterioration or PD, or until treatment was discontinued for another reason (up to Cycle 53).

Secondary

MTD Expansion Phase, AUCinf: Area Under the Plasma Concentration-time Curve Extrapolated to Infinity for MLN4924

Posted

Mean

Standard Deviation

hr*ng/mL

Cycle 1 Day 1 pre-dose and at multiple time points (up to 24 hours) post-dose; Cycle 1 Day 5 pre-dose and at multiple time points (up to 48 hours) post-dose (Cycle length = 28 days)

ID	Title	Description
OG000	MLN4924 20 mg/m^2 + Azacitidine 75 mg/m^2 Intravenous	MLN4924 20 mg/m^2, infusion, intravenously, once on Days 1, 3, and 5 in combination with azacitidine 75 mg/m^2, infusion, intravenously, once on Days 1 through 5, 8 and 9 before administration of MLN4924 in a 28-day treatment cycle up to symptomatic deterioration or progressive disease (PD), or until treatment was discontinued for another reason (up to Cycle 53).
OG001	MLN4924 20 mg/m^2 + Azacitidine 75 mg/m^2 Subcutaneous	MLN4924 20 mg/m^2, infusion, intravenously, once on Days 1, 3, and 5 in combination with azacitidine 75 mg/m^2, infusion, subcutaneously, once on Days 1 through 5, 8 and 9 before administration of MLN4924 in a 28-day treatment cycle up to symptomatic deterioration or PD, or until treatment was discontinued for another reason (up to Cycle 53).

Secondary

Dose-escalation Phase, Lambdaz: Terminal Disposition Phase Rate Constant for MLN4924

Posted

Mean

Standard Deviation

1 per hour (1/hr)

Cycle 1 Day 1 pre-dose and at multiple time points (up to 24 hours) post-dose; Cycle 1 Day 5 pre-dose and at multiple time points (up to 48 hours) post-dose (Cycle length = 28 days)

ID	Title	Description
OG000	MLN4924 20 mg/m^2 + Azacitidine 75 mg/m^2 Intravenous	MLN4924 20 mg/m^2, infusion, intravenously, once on Days 1, 3, and 5 in combination with azacitidine 75 mg/m^2, infusion, intravenously, once on Days 1 through 5, 8 and 9 before administration of MLN4924 in a 28-day treatment cycle up to symptomatic deterioration or progressive disease (PD), or until treatment was discontinued for another reason (up to Cycle 53).
OG001	MLN4924 30 mg/m^2 + Azacitidine 75 mg/m^2 Intravenous	MLN4924 30 mg/m^2, infusion, intravenously, once on Days 1, 3, and 5 in combination with azacitidine 75 mg/m^2, infusion, intravenously, once on Days 1 through 5, 8 and 9 before administration of MLN4924 in a 28-day treatment cycle up to symptomatic deterioration or PD, or until treatment was discontinued for another reason (up to Cycle 53).

Secondary

MTD Expansion Phase, Lambdaz: Terminal Disposition Phase Rate Constant for MLN4924

Posted

Mean

Standard Deviation

1/hr

Cycle 1 Day 1 pre-dose and at multiple time points (up to 24 hours) post-dose; Cycle 1 Day 5 pre-dose and at multiple time points (up to 48 hours) post-dose (Cycle length = 28 days)

ID	Title	Description
OG000	MLN4924 20 mg/m^2 + Azacitidine 75 mg/m^2 Intravenous	MLN4924 20 mg/m^2, infusion, intravenously, once on Days 1, 3, and 5 in combination with azacitidine 75 mg/m^2, infusion, intravenously, once on Days 1 through 5, 8 and 9 before administration of MLN4924 in a 28-day treatment cycle up to symptomatic deterioration or progressive disease (PD), or until treatment was discontinued for another reason (up to Cycle 53).
OG001	MLN4924 20 mg/m^2 + Azacitidine 75 mg/m^2 Subcutaneous	MLN4924 20 mg/m^2, infusion, intravenously, once on Days 1, 3, and 5 in combination with azacitidine 75 mg/m^2, infusion, subcutaneously, once on Days 1 through 5, 8 and 9 before administration of MLN4924 in a 28-day treatment cycle up to symptomatic deterioration or PD, or until treatment was discontinued for another reason (up to Cycle 53).

Secondary

Dose-escalation Phase, t1/2: Terminal Disposition Phase Half-life for MLN4924

Posted

Mean

Standard Deviation

hour

Cycle 1 Day 1 pre-dose and at multiple time points (up to 24 hours) post-dose; Cycle 1 Day 5 pre-dose and at multiple time points (up to 48 hours) post-dose (Cycle length = 28 days)

ID	Title	Description
OG000	MLN4924 20 mg/m^2 + Azacitidine 75 mg/m^2 Intravenous	MLN4924 20 mg/m^2, infusion, intravenously, once on Days 1, 3, and 5 in combination with azacitidine 75 mg/m^2, infusion, intravenously, once on Days 1 through 5, 8 and 9 before administration of MLN4924 in a 28-day treatment cycle up to symptomatic deterioration or progressive disease (PD), or until treatment was discontinued for another reason (up to Cycle 53).
OG001	MLN4924 30 mg/m^2 + Azacitidine 75 mg/m^2 Intravenous	MLN4924 30 mg/m^2, infusion, intravenously, once on Days 1, 3, and 5 in combination with azacitidine 75 mg/m^2, infusion, intravenously, once on Days 1 through 5, 8 and 9 before administration of MLN4924 in a 28-day treatment cycle up to symptomatic deterioration or PD, or until treatment was discontinued for another reason (up to Cycle 53).

Secondary

MTD Expansion Phase, t1/2: Terminal Disposition Phase Half-life for MLN4924

Posted

Mean

Standard Deviation

hour

Cycle 1 Day 1 pre-dose and at multiple time points (up to 24 hours) post-dose; Cycle 1 Day 5 pre-dose and at multiple time points (up to 48 hours) post-dose (Cycle length = 28 days)

ID	Title	Description
OG000	MLN4924 20 mg/m^2 + Azacitidine 75 mg/m^2 Intravenous	MLN4924 20 mg/m^2, infusion, intravenously, once on Days 1, 3, and 5 in combination with azacitidine 75 mg/m^2, infusion, intravenously, once on Days 1 through 5, 8 and 9 before administration of MLN4924 in a 28-day treatment cycle up to symptomatic deterioration or progressive disease (PD), or until treatment was discontinued for another reason (up to Cycle 53).
OG001	MLN4924 20 mg/m^2 + Azacitidine 75 mg/m^2 Subcutaneous	MLN4924 20 mg/m^2, infusion, intravenously, once on Days 1, 3, and 5 in combination with azacitidine 75 mg/m^2, infusion, subcutaneously, once on Days 1 through 5, 8 and 9 before administration of MLN4924 in a 28-day treatment cycle up to symptomatic deterioration or PD, or until treatment was discontinued for another reason (up to Cycle 53).

Secondary

Dose-escalation Phase, Rac: Observed Accumulation Ratio for MLN4924

Posted

Mean

Standard Deviation

ratio

Cycle 1 Day 1 pre-dose and at multiple time points (up to 24 hours) post-dose; Cycle 1 Day 5 pre-dose and at multiple time points (up to 48 hours) post-dose (Cycle length = 28 days)

ID	Title	Description
OG000	MLN4924 20 mg/m^2 + Azacitidine 75 mg/m^2 Intravenous	MLN4924 20 mg/m^2, infusion, intravenously, once on Days 1, 3, and 5 in combination with azacitidine 75 mg/m^2, infusion, intravenously, once on Days 1 through 5, 8 and 9 before administration of MLN4924 in a 28-day treatment cycle up to symptomatic deterioration or progressive disease (PD), or until treatment was discontinued for another reason (up to Cycle 53).
OG001	MLN4924 30 mg/m^2 + Azacitidine 75 mg/m^2 Intravenous	MLN4924 30 mg/m^2, infusion, intravenously, once on Days 1, 3, and 5 in combination with azacitidine 75 mg/m^2, infusion, intravenously, once on Days 1 through 5, 8 and 9 before administration of MLN4924 in a 28-day treatment cycle up to symptomatic deterioration or PD, or until treatment was discontinued for another reason (up to Cycle 53).

Secondary

MTD Expansion Phase, Rac: Observed Accumulation Ratio for MLN4924

Posted

Mean

Standard Deviation

ratio

Cycle 1 Day 1 pre-dose and at multiple time points (up to 24 hours) post-dose; Cycle 1 Day 5 pre-dose and at multiple time points (up to 48 hours) post-dose (Cycle length = 28 days)

ID	Title	Description
OG000	MLN4924 20 mg/m^2 + Azacitidine 75 mg/m^2 Intravenous	MLN4924 20 mg/m^2, infusion, intravenously, once on Days 1, 3, and 5 in combination with azacitidine 75 mg/m^2, infusion, intravenously, once on Days 1 through 5, 8 and 9 before administration of MLN4924 in a 28-day treatment cycle up to symptomatic deterioration or progressive disease (PD), or until treatment was discontinued for another reason (up to Cycle 53).
OG001	MLN4924 20 mg/m^2 + Azacitidine 75 mg/m^2 Subcutaneous	MLN4924 20 mg/m^2, infusion, intravenously, once on Days 1, 3, and 5 in combination with azacitidine 75 mg/m^2, infusion, subcutaneously, once on Days 1 through 5, 8 and 9 before administration of MLN4924 in a 28-day treatment cycle up to symptomatic deterioration or PD, or until treatment was discontinued for another reason (up to Cycle 53).

Secondary

Dose-escalation Phase, CLp: Systemic Clearance for MLN4924

Posted

Mean

Standard Deviation

liter per hour (L/hr)

Cycle 1 Day 1 pre-dose and at multiple time points (up to 24 hours) post-dose; Cycle 1 Day 5 pre-dose and at multiple time points (up to 48 hours) post-dose (Cycle length = 28 days)

ID	Title	Description
OG000	MLN4924 20 mg/m^2 + Azacitidine 75 mg/m^2 Intravenous	MLN4924 20 mg/m^2, infusion, intravenously, once on Days 1, 3, and 5 in combination with azacitidine 75 mg/m^2, infusion, intravenously, once on Days 1 through 5, 8 and 9 before administration of MLN4924 in a 28-day treatment cycle up to symptomatic deterioration or progressive disease (PD), or until treatment was discontinued for another reason (up to Cycle 53).
OG001	MLN4924 30 mg/m^2 + Azacitidine 75 mg/m^2 Intravenous	MLN4924 30 mg/m^2, infusion, intravenously, once on Days 1, 3, and 5 in combination with azacitidine 75 mg/m^2, infusion, intravenously, once on Days 1 through 5, 8 and 9 before administration of MLN4924 in a 28-day treatment cycle up to symptomatic deterioration or PD, or until treatment was discontinued for another reason (up to Cycle 53).

Secondary

MTD Expansion Phase, CLp: Systemic Clearance for MLN4924

Posted

Mean

Standard Deviation

L/hr

Cycle 1 Day 1 pre-dose and at multiple time points (up to 24 hours) post-dose; Cycle 1 Day 5 pre-dose and at multiple time points (up to 48 hours) post-dose (Cycle length = 28 days)

ID	Title	Description
OG000	MLN4924 20 mg/m^2 + Azacitidine 75 mg/m^2 Intravenous	MLN4924 20 mg/m^2, infusion, intravenously, once on Days 1, 3, and 5 in combination with azacitidine 75 mg/m^2, infusion, intravenously, once on Days 1 through 5, 8 and 9 before administration of MLN4924 in a 28-day treatment cycle up to symptomatic deterioration or progressive disease (PD), or until treatment was discontinued for another reason (up to Cycle 53).
OG001	MLN4924 20 mg/m^2 + Azacitidine 75 mg/m^2 Subcutaneous	MLN4924 20 mg/m^2, infusion, intravenously, once on Days 1, 3, and 5 in combination with azacitidine 75 mg/m^2, infusion, subcutaneously, once on Days 1 through 5, 8 and 9 before administration of MLN4924 in a 28-day treatment cycle up to symptomatic deterioration or PD, or until treatment was discontinued for another reason (up to Cycle 53).

Secondary

Dose-escalation Phase, Vss: Volume of Distribution at Steady-state for MLN4924

Posted

Mean

Standard Deviation

liter (L)

Cycle 1 Day 1 pre-dose and at multiple time points (up to 24 hours) post-dose; Cycle 1 Day 5 pre-dose and at multiple time points (up to 48 hours) post-dose (Cycle length = 28 days)

ID	Title	Description
OG000	MLN4924 20 mg/m^2 + Azacitidine 75 mg/m^2 Intravenous	MLN4924 20 mg/m^2, infusion, intravenously, once on Days 1, 3, and 5 in combination with azacitidine 75 mg/m^2, infusion, intravenously, once on Days 1 through 5, 8 and 9 before administration of MLN4924 in a 28-day treatment cycle up to symptomatic deterioration or progressive disease (PD), or until treatment was discontinued for another reason (up to Cycle 53).
OG001	MLN4924 30 mg/m^2 + Azacitidine 75 mg/m^2 Intravenous	MLN4924 30 mg/m^2, infusion, intravenously, once on Days 1, 3, and 5 in combination with azacitidine 75 mg/m^2, infusion, intravenously, once on Days 1 through 5, 8 and 9 before administration of MLN4924 in a 28-day treatment cycle up to symptomatic deterioration or PD, or until treatment was discontinued for another reason (up to Cycle 53).

Secondary

MTD Expansion Phase, Vss: Volume of Distribution at Steady-state for MLN4924

Posted

Mean

Standard Deviation

liter

Cycle 1 Day 1 pre-dose and at multiple time points (up to 24 hours) post-dose; Cycle 1 Day 5 pre-dose and at multiple time points (up to 48 hours) post-dose (Cycle length = 28 days)

ID	Title	Description
OG000	MLN4924 20 mg/m^2 + Azacitidine 75 mg/m^2 Intravenous	MLN4924 20 mg/m^2, infusion, intravenously, once on Days 1, 3, and 5 in combination with azacitidine 75 mg/m^2, infusion, intravenously, once on Days 1 through 5, 8 and 9 before administration of MLN4924 in a 28-day treatment cycle up to symptomatic deterioration or progressive disease (PD), or until treatment was discontinued for another reason (up to Cycle 53).
OG001	MLN4924 20 mg/m^2 + Azacitidine 75 mg/m^2 Subcutaneous	MLN4924 20 mg/m^2, infusion, intravenously, once on Days 1, 3, and 5 in combination with azacitidine 75 mg/m^2, infusion, subcutaneously, once on Days 1 through 5, 8 and 9 before administration of MLN4924 in a 28-day treatment cycle up to symptomatic deterioration or PD, or until treatment was discontinued for another reason (up to Cycle 53).

Secondary

Best Overall Response Rate

Disease response was based on best overall response as determined by an investigator based on revised recommendations of the International Working Group (IWG) Response Criteria for AML. Best overall response rate was defined as percentage of participants who had complete response (CR), partial response (PR), or CR/remission with incomplete blood count recovery (Cri). CR: free of leukemia-related symptoms, absolute neutrophil count (ANC) greater than (>)1.0*10^9 per liter (/L), platelet count greater than or equal to (>=) 100*10^9/L, normal bone marrow with <5 percent (%) blasts and no Auer rods. CRi: As per CR but with residual thrombocytopenia (platelet count <100*10^9/L) or residual neutropenia (ANC <1.0*10^9/L). PR: >=50% decrease bone marrow blasts to 5 to 25% abnormal cells, or CR with less than or equal to (<=) 5% blasts if Auer rods present.

The response-evaluable population was defined as all participants who received at least 1 dose of study drug, had measurable disease at baseline, and had at least 1 post baseline disease assessment. Participants who were evaluable at a particular time point for this outcome measure were included in the assessment.

Posted

Number

percentage of participants

Cycle(C)1Day(D)22 and at C2 between D20 and 28 and at C4 and beyond C4 after completion of every 3rd C between D15 and 28 up to 30 days after last dose of study drug/before start of subsequent antineoplastic therapy, if that occurred sooner(up to 5 years)

ID	Title	Description
OG000	MLN4924 20 mg/m^2 + Azacitidine 75 mg/m^2 Intravenous	MLN4924 20 mg/m^2, infusion, intravenously, once on Days 1, 3, and 5 in combination with azacitidine 75 mg/m^2, infusion, intravenously, once on Days 1 through 5, 8 and 9 before administration of MLN4924 in a 28-day treatment cycle up to symptomatic deterioration or progressive disease (PD), or until treatment was discontinued for another reason (up to Cycle 53).

Secondary

Duration of Response

The duration of response was defined in participants with disease response (CR, CRi, or PR) as the time between the first documentation of response and disease progression. Duration of response was determined by an investigator based on revised recommendations of the IWG Response Criteria for AML. CR: free of leukemia-related symptoms, absolute neutrophil count (ANC) greater than (>)1.0*10^9 per liter (/L), platelet count greater than or equal to (>=) 100*10^9/L, normal bone marrow with <5 percent (%) blasts and no Auer rods. CRi: As per CR but with residual thrombocytopenia (platelet count <100*10^9/L) or residual neutropenia (ANC <1.0*10^9/L). PR: >=50% decrease bone marrow blasts to 5 to 25% abnormal cells, or CR with less than or equal to (<=) 5% blasts if Auer rods present.

Posted

Median

95% Confidence Interval

months

From the date of first documented CR, PR or CRi up to the date of first disease progression (Up to 5 years)

ID	Title	Description
OG000	MLN4924 20 mg/m^2 + Azacitidine 75 mg/m^2 Intravenous	MLN4924 20 mg/m^2, infusion, intravenously, once on Days 1, 3, and 5 in combination with azacitidine 75 mg/m^2, infusion, intravenously, once on Days 1 through 5, 8 and 9 before administration of MLN4924 in a 28-day treatment cycle up to symptomatic deterioration or progressive disease (PD), or until treatment was discontinued for another reason (up to Cycle 53).

Secondary

Overall Survival

Overall survival was defined as the time from the first dose of study drug to the date of death. The Kaplan-Meier method was used to estimate overall survival, along with the corresponding 95% confidence interval.

The safety population was defined as all enrolled participants who receive at least 1 dose of any study drug, MLN4924 or azacitidine.

Posted

Median

95% Confidence Interval

months

From the first dose of study drug up to date of death (up to 5 years)

ID	Title	Description
OG000	MLN4924 20 mg/m^2 + Azacitidine 75 mg/m^2 Intravenous	MLN4924 20 mg/m^2, infusion, intravenously, once on Days 1, 3, and 5 in combination with azacitidine 75 mg/m^2, infusion, intravenously, once on Days 1 through 5, 8 and 9 before administration of MLN4924 in a 28-day treatment cycle up to symptomatic deterioration or progressive disease (PD), or until treatment was discontinued for another reason (up to Cycle 53).
OG001	MLN4924 20 mg/m^2 + Azacitidine 75 mg/m^2 Subcutaneous	MLN4924 20 mg/m^2, infusion, intravenously, once on Days 1, 3, and 5 in combination with azacitidine 75 mg/m^2, infusion, subcutaneously, once on Days 1 through 5, 8 and 9 before administration of MLN4924 in a 28-day treatment cycle up to symptomatic deterioration or PD, or until treatment was discontinued for another reason (up to Cycle 53).
OG002

Secondary

Thirty-day Mortality Rate

The safety population was defined as all enrolled participants who receive at least 1 dose of any study drug, MLN4924 or azacitidine.

Posted

Number

percentage of participants

30 days after the first dose of study drug in Cycle 1 (Cycle Length=28 days)

ID	Title	Description
OG000	MLN4924 20 mg/m^2 + Azacitidine 75 mg/m^2 Intravenous	MLN4924 20 mg/m^2, infusion, intravenously, once on Days 1, 3, and 5 in combination with azacitidine 75 mg/m^2, infusion, intravenously, once on Days 1 through 5, 8 and 9 before administration of MLN4924 in a 28-day treatment cycle up to symptomatic deterioration or progressive disease (PD), or until treatment was discontinued for another reason (up to Cycle 53).
OG001	MLN4924 20 mg/m^2 + Azacitidine 75 mg/m^2 Subcutaneous	MLN4924 20 mg/m^2, infusion, intravenously, once on Days 1, 3, and 5 in combination with azacitidine 75 mg/m^2, infusion, subcutaneously, once on Days 1 through 5, 8 and 9 before administration of MLN4924 in a 28-day treatment cycle up to symptomatic deterioration or PD, or until treatment was discontinued for another reason (up to Cycle 53).
OG002	MLN4924 30 mg/m^2 + Azacitidine 75 mg/m^2 Intravenous	MLN4924 30 mg/m^2, infusion, intravenously, once on Days 1, 3, and 5 in combination with azacitidine 75 mg/m^2, infusion, intravenously, once on Days 1 through 5, 8 and 9 before administration of MLN4924 in a 28-day treatment cycle up to symptomatic deterioration or PD, or until treatment was discontinued for another reason (up to Cycle 53).

Secondary

Sixty-day Mortality Rate

No participant was analyzed since this outcome measure was not planned to be assessed but added in the protocol summary by error.

Posted

60 days after the first dose of study drug on Cycle 1 (Cycle Length=28 days)

ID	Title	Description
OG000	MLN4924 20 mg/m^2 + Azacitidine 75 mg/m^2 Intravenous	MLN4924 20 mg/m^2, infusion, intravenously, once on Days 1, 3, and 5 in combination with azacitidine 75 mg/m^2, infusion, intravenously, once on Days 1 through 5, 8 and 9 before administration of MLN4924 in a 28-day treatment cycle up to symptomatic deterioration or progressive disease (PD), or until treatment was discontinued for another reason (up to Cycle 53).
OG001	MLN4924 20 mg/m^2 + Azacitidine 75 mg/m^2 Subcutaneous	MLN4924 20 mg/m^2, infusion, intravenously, once on Days 1, 3, and 5 in combination with azacitidine 75 mg/m^2, infusion, subcutaneously, once on Days 1 through 5, 8 and 9 before administration of MLN4924 in a 28-day treatment cycle up to symptomatic deterioration or PD, or until treatment was discontinued for another reason (up to Cycle 53).
OG002	MLN4924 30 mg/m^2 + Azacitidine 75 mg/m^2 Intravenous	MLN4924 30 mg/m^2, infusion, intravenously, once on Days 1, 3, and 5 in combination with azacitidine 75 mg/m^2, infusion, intravenously, once on Days 1 through 5, 8 and 9 before administration of MLN4924 in a 28-day treatment cycle up to symptomatic deterioration or PD, or until treatment was discontinued for another reason (up to Cycle 53).

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Pneumonia	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG0003 affected32 at risk EG0014 affected29 at risk EG0022 affected3 at risk
Sepsis	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG0001 affected32 at risk EG0012 affected29 at risk EG0020 affected3 at risk
Bacteraemia	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG0001 affected32 at risk EG0010 affected29 at risk EG0020 affected3 at risk
Septic shock	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG0001 affected32 at risk EG0010 affected29 at risk EG0020 affected3 at risk
Diverticulitis	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG0000 affected32 at risk EG0012 affected29 at risk EG0020 affected3 at risk
Peritonitis	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG0001 affected32 at risk EG0010 affected29 at risk EG0020 affected3 at risk
Cellulitis	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG0001 affected32 at risk EG0011 affected29 at risk EG0020 affected3 at risk
Gingivitis	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG0001 affected32 at risk EG0010 affected29 at risk EG0020 affected3 at risk
Device related infection	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG0001 affected32 at risk EG0010 affected29 at risk EG0020 affected3 at risk
Pneumonia legionella	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG0001 affected32 at risk EG0010 affected29 at risk EG0020 affected3 at risk
Pseudomonal bacteraemia	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG0000 affected32 at risk EG0011 affected29 at risk EG0020 affected3 at risk
Pharyngitis	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG0000 affected32 at risk EG0010 affected29 at risk EG0021 affected3 at risk
Febrile neutropenia	Blood and lymphatic system disorders	MedDRA 19.0	Systematic Assessment	EG0007 affected32 at risk EG0019 affected29 at risk EG0021 affected3 at risk
Anaemia	Blood and lymphatic system disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected32 at risk EG0010 affected29 at risk EG0020 affected3 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected32 at risk EG0010 affected29 at risk EG0020 affected3 at risk
Pyrexia	General disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected32 at risk EG0013 affected29 at risk EG0020 affected3 at risk
Multiple organ dysfunction syndrome	General disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected32 at risk EG0011 affected29 at risk EG0020 affected3 at risk
Asthenia	General disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected32 at risk EG0010 affected29 at risk EG0020 affected3 at risk
Death	General disorders	MedDRA 19.0	Systematic Assessment	EG0000 affected32 at risk EG0011 affected29 at risk EG0020 affected3 at risk
Systemic inflammatory response syndrome	General disorders	MedDRA 19.0	Systematic Assessment	EG0000 affected32 at risk EG0011 affected29 at risk EG0020 affected3 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 19.0	Systematic Assessment	EG0002 affected32 at risk EG0010 affected29 at risk EG0020 affected3 at risk
Acute respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA 19.0	Systematic Assessment	EG0000 affected32 at risk EG0011 affected29 at risk EG0020 affected3 at risk
Respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected32 at risk EG0010 affected29 at risk EG0020 affected3 at risk
Hypoxia	Respiratory, thoracic and mediastinal disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected32 at risk EG0010 affected29 at risk EG0020 affected3 at risk
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected32 at risk EG0010 affected29 at risk EG0020 affected3 at risk
Acute pulmonary oedema	Respiratory, thoracic and mediastinal disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected32 at risk EG0010 affected29 at risk EG0020 affected3 at risk
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected32 at risk EG0010 affected29 at risk EG0020 affected3 at risk
Transaminases increased	Investigations	MedDRA 19.0	Systematic Assessment	EG0000 affected32 at risk EG0012 affected29 at risk EG0020 affected3 at risk
Alanine aminotransferase increased	Investigations	MedDRA 19.0	Systematic Assessment	EG0001 affected32 at risk EG0010 affected29 at risk EG0020 affected3 at risk
Aspartate aminotransferase increased	Investigations	MedDRA 19.0	Systematic Assessment	EG0001 affected32 at risk EG0010 affected29 at risk EG0020 affected3 at risk
Electrocardiogram QT prolonged	Investigations	MedDRA 19.0	Systematic Assessment	EG0000 affected32 at risk EG0011 affected29 at risk EG0020 affected3 at risk
Electrocardiogram T wave inversion	Investigations	MedDRA 19.0	Systematic Assessment	EG0000 affected32 at risk EG0011 affected29 at risk EG0020 affected3 at risk
Platelet count decreased	Investigations	MedDRA 19.0	Systematic Assessment	EG0001 affected32 at risk EG0010 affected29 at risk EG0020 affected3 at risk
Blood creatinine increased	Investigations	MedDRA 19.0	Systematic Assessment	EG0000 affected32 at risk EG0010 affected29 at risk EG0021 affected3 at risk
Acute myeloid leukaemia	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 19.0	Systematic Assessment	EG0003 affected32 at risk EG0013 affected29 at risk EG0021 affected3 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 19.0	Systematic Assessment	EG0000 affected32 at risk EG0011 affected29 at risk EG0020 affected3 at risk
Dysphagia	Gastrointestinal disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected32 at risk EG0010 affected29 at risk EG0020 affected3 at risk
Diverticular perforation	Gastrointestinal disorders	MedDRA 19.0	Systematic Assessment	EG0000 affected32 at risk EG0011 affected29 at risk EG0020 affected3 at risk
Intestinal perforation	Gastrointestinal disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected32 at risk EG0010 affected29 at risk EG0020 affected3 at risk
Oral pain	Gastrointestinal disorders	MedDRA 19.0	Systematic Assessment	EG0000 affected32 at risk EG0011 affected29 at risk EG0020 affected3 at risk
Mental status changes	Psychiatric disorders	MedDRA 19.0	Systematic Assessment	EG0000 affected32 at risk EG0012 affected29 at risk EG0020 affected3 at risk
Confusional state	Psychiatric disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected32 at risk EG0010 affected29 at risk EG0020 affected3 at risk
Delirium	Psychiatric disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected32 at risk EG0010 affected29 at risk EG0020 affected3 at risk
Acute myocardial infarction	Cardiac disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected32 at risk EG0011 affected29 at risk EG0020 affected3 at risk
Cardiac failure congestive	Cardiac disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected32 at risk EG0010 affected29 at risk EG0020 affected3 at risk
Syncope	Nervous system disorders	MedDRA 19.0	Systematic Assessment	EG0000 affected32 at risk EG0011 affected29 at risk EG0020 affected3 at risk
Encephalopathy	Nervous system disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected32 at risk EG0010 affected29 at risk EG0020 affected3 at risk
Sciatica	Nervous system disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected32 at risk EG0010 affected29 at risk EG0020 affected3 at risk
Embolism	Vascular disorders	MedDRA 19.0	Systematic Assessment	EG0002 affected32 at risk EG0010 affected29 at risk EG0020 affected3 at risk
Haematoma	Vascular disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected32 at risk EG0010 affected29 at risk EG0020 affected3 at risk
Deep vein thrombosis	Vascular disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected32 at risk EG0010 affected29 at risk EG0020 affected3 at risk
Hypotension	Vascular disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected32 at risk EG0010 affected29 at risk EG0020 affected3 at risk
Muscular weakness	Musculoskeletal and connective tissue disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected32 at risk EG0010 affected29 at risk EG0020 affected3 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected32 at risk EG0010 affected29 at risk EG0020 affected3 at risk
Cholecystitis	Hepatobiliary disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected32 at risk EG0010 affected29 at risk EG0020 affected3 at risk
Fall	Injury, poisoning and procedural complications	MedDRA 19.0	Systematic Assessment	EG0001 affected32 at risk EG0010 affected29 at risk EG0020 affected3 at risk
Hyponatraemia	Metabolism and nutrition disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected32 at risk EG0010 affected29 at risk EG0020 affected3 at risk
Squamous cell carcinoma of skin	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 19.0	Systematic Assessment	EG0000 affected32 at risk EG0011 affected29 at risk EG0020 affected3 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 19.0	Systematic Assessment	EG00014 affected32 at risk EG00110 affected29 at risk EG0021 affected3 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA 19.0	Systematic Assessment	EG00010 affected32 at risk EG0018 affected29 at risk EG0022 affected3 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA 19.0	Systematic Assessment	EG00010 affected32 at risk EG0016 affected29 at risk EG0020 affected3 at risk
Leukopenia	Blood and lymphatic system disorders	MedDRA 19.0	Systematic Assessment	EG0005 affected32 at risk EG0012 affected29 at risk EG0021 affected3 at risk
Febrile neutropenia	Blood and lymphatic system disorders	MedDRA 19.0	Systematic Assessment	EG0000 affected32 at risk EG0014 affected29 at risk EG0021 affected3 at risk
Lymphopenia	Blood and lymphatic system disorders	MedDRA 19.0	Systematic Assessment	EG0002 affected32 at risk EG0012 affected29 at risk EG0021 affected3 at risk
Leukocytosis	Blood and lymphatic system disorders	MedDRA 19.0	Systematic Assessment	EG0000 affected32 at risk EG0012 affected29 at risk EG0020 affected3 at risk
Tachycardia	Cardiac disorders	MedDRA 19.0	Systematic Assessment	EG0004 affected32 at risk EG0011 affected29 at risk EG0020 affected3 at risk
Palpitations	Cardiac disorders	MedDRA 19.0	Systematic Assessment	EG0002 affected32 at risk EG0010 affected29 at risk EG0020 affected3 at risk
Dry eye	Eye disorders	MedDRA 19.0	Systematic Assessment	EG0003 affected32 at risk EG0011 affected29 at risk EG0020 affected3 at risk
Constipation	Gastrointestinal disorders	MedDRA 19.0	Systematic Assessment	EG00018 affected32 at risk EG00112 affected29 at risk EG0021 affected3 at risk
Nausea	Gastrointestinal disorders	MedDRA 19.0	Systematic Assessment	EG00015 affected32 at risk EG00111 affected29 at risk EG0021 affected3 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 19.0	Systematic Assessment	EG0006 affected32 at risk EG0019 affected29 at risk EG0020 affected3 at risk
Vomiting	Gastrointestinal disorders	MedDRA 19.0	Systematic Assessment	EG0006 affected32 at risk EG0019 affected29 at risk EG0020 affected3 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 19.0	Systematic Assessment	EG0004 affected32 at risk EG0013 affected29 at risk EG0020 affected3 at risk
Stomatitis	Gastrointestinal disorders	MedDRA 19.0	Systematic Assessment	EG0002 affected32 at risk EG0014 affected29 at risk EG0020 affected3 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected32 at risk EG0012 affected29 at risk EG0020 affected3 at risk
Dyspepsia	Gastrointestinal disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected32 at risk EG0012 affected29 at risk EG0020 affected3 at risk
Gastrooesophageal reflux disease	Gastrointestinal disorders	MedDRA 19.0	Systematic Assessment	EG0002 affected32 at risk EG0011 affected29 at risk EG0020 affected3 at risk
Mouth ulceration	Gastrointestinal disorders	MedDRA 19.0	Systematic Assessment	EG0002 affected32 at risk EG0011 affected29 at risk EG0020 affected3 at risk
Toothache	Gastrointestinal disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected32 at risk EG0012 affected29 at risk EG0020 affected3 at risk
Flatulence	Gastrointestinal disorders	MedDRA 19.0	Systematic Assessment	EG0000 affected32 at risk EG0012 affected29 at risk EG0020 affected3 at risk
Haematochezia	Gastrointestinal disorders	MedDRA 19.0	Systematic Assessment	EG0000 affected32 at risk EG0012 affected29 at risk EG0020 affected3 at risk
Oesophageal pain	Gastrointestinal disorders	MedDRA 19.0	Systematic Assessment	EG0000 affected32 at risk EG0012 affected29 at risk EG0020 affected3 at risk
Fatigue	General disorders	MedDRA 19.0	Systematic Assessment	EG00016 affected32 at risk EG00110 affected29 at risk EG0021 affected3 at risk
Pyrexia	General disorders	MedDRA 19.0	Systematic Assessment	EG0009 affected32 at risk EG0015 affected29 at risk EG0020 affected3 at risk
Oedema peripheral	General disorders	MedDRA 19.0	Systematic Assessment	EG0005 affected32 at risk EG0015 affected29 at risk EG0021 affected3 at risk
Chills	General disorders	MedDRA 19.0	Systematic Assessment	EG0003 affected32 at risk EG0016 affected29 at risk EG0020 affected3 at risk
Asthenia	General disorders	MedDRA 19.0	Systematic Assessment	EG0003 affected32 at risk EG0012 affected29 at risk EG0020 affected3 at risk
Injection site erythema	General disorders	MedDRA 19.0	Systematic Assessment	EG0000 affected32 at risk EG0015 affected29 at risk EG0020 affected3 at risk
Injection site pain	General disorders	MedDRA 19.0	Systematic Assessment	EG0000 affected32 at risk EG0015 affected29 at risk EG0020 affected3 at risk
Pain	General disorders	MedDRA 19.0	Systematic Assessment	EG0003 affected32 at risk EG0012 affected29 at risk EG0020 affected3 at risk
Injection site rash	General disorders	MedDRA 19.0	Systematic Assessment	EG0000 affected32 at risk EG0013 affected29 at risk EG0020 affected3 at risk
Peripheral swelling	General disorders	MedDRA 19.0	Systematic Assessment	EG0003 affected32 at risk EG0010 affected29 at risk EG0020 affected3 at risk
Gait disturbance	General disorders	MedDRA 19.0	Systematic Assessment	EG0002 affected32 at risk EG0010 affected29 at risk EG0020 affected3 at risk
Ill-defined disorder	General disorders	MedDRA 19.0	Systematic Assessment	EG0000 affected32 at risk EG0012 affected29 at risk EG0020 affected3 at risk
Injection site reaction	General disorders	MedDRA 19.0	Systematic Assessment	EG0000 affected32 at risk EG0012 affected29 at risk EG0020 affected3 at risk
Non-cardiac chest pain	General disorders	MedDRA 19.0	Systematic Assessment	EG0002 affected32 at risk EG0010 affected29 at risk EG0020 affected3 at risk
Pneumonia	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG0003 affected32 at risk EG0013 affected29 at risk EG0020 affected3 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG0003 affected32 at risk EG0013 affected29 at risk EG0020 affected3 at risk
Urinary tract infection	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG0004 affected32 at risk EG0012 affected29 at risk EG0020 affected3 at risk
Sinusitis	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG0003 affected32 at risk EG0011 affected29 at risk EG0020 affected3 at risk
Cellulitis	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG0000 affected32 at risk EG0013 affected29 at risk EG0020 affected3 at risk
Rhinovirus infection	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG0001 affected32 at risk EG0012 affected29 at risk EG0020 affected3 at risk
Folliculitis	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG0002 affected32 at risk EG0010 affected29 at risk EG0020 affected3 at risk
Pharyngitis	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG0000 affected32 at risk EG0012 affected29 at risk EG0020 affected3 at risk
Fall	Injury, poisoning and procedural complications	MedDRA 19.0	Systematic Assessment	EG0007 affected32 at risk EG0013 affected29 at risk EG0020 affected3 at risk
Transfusion reaction	Injury, poisoning and procedural complications	MedDRA 19.0	Systematic Assessment	EG0002 affected32 at risk EG0012 affected29 at risk EG0020 affected3 at risk
Laceration	Injury, poisoning and procedural complications	MedDRA 19.0	Systematic Assessment	EG0002 affected32 at risk EG0010 affected29 at risk EG0020 affected3 at risk
Alanine aminotransferase increased	Investigations	MedDRA 19.0	Systematic Assessment	EG0006 affected32 at risk EG0013 affected29 at risk EG0022 affected3 at risk
Blood creatinine increased	Investigations	MedDRA 19.0	Systematic Assessment	EG0006 affected32 at risk EG0013 affected29 at risk EG0021 affected3 at risk
Weight decreased	Investigations	MedDRA 19.0	Systematic Assessment	EG0004 affected32 at risk EG0014 affected29 at risk EG0020 affected3 at risk
Aspartate aminotransferase increased	Investigations	MedDRA 19.0	Systematic Assessment	EG0005 affected32 at risk EG0012 affected29 at risk EG0022 affected3 at risk
Blood alkaline phosphatase increased	Investigations	MedDRA 19.0	Systematic Assessment	EG0007 affected32 at risk EG0010 affected29 at risk EG0022 affected3 at risk
Neutrophil count decreased	Investigations	MedDRA 19.0	Systematic Assessment	EG0006 affected32 at risk EG0011 affected29 at risk EG0020 affected3 at risk
Platelet count decreased	Investigations	MedDRA 19.0	Systematic Assessment	EG0005 affected32 at risk EG0012 affected29 at risk EG0020 affected3 at risk
White blood cell count decreased	Investigations	MedDRA 19.0	Systematic Assessment	EG0003 affected32 at risk EG0012 affected29 at risk EG0020 affected3 at risk
Blood bilirubin increased	Investigations	MedDRA 19.0	Systematic Assessment	EG0003 affected32 at risk EG0011 affected29 at risk EG0021 affected3 at risk
Lymphocyte count decreased	Investigations	MedDRA 19.0	Systematic Assessment	EG0002 affected32 at risk EG0012 affected29 at risk EG0020 affected3 at risk
Gamma-glutamyltransferase increased	Investigations	MedDRA 19.0	Systematic Assessment	EG0001 affected32 at risk EG0012 affected29 at risk EG0021 affected3 at risk
White blood cell count increased	Investigations	MedDRA 19.0	Systematic Assessment	EG0001 affected32 at risk EG0012 affected29 at risk EG0020 affected3 at risk
Activated partial thromboplastin time prolonged	Investigations	MedDRA 19.0	Systematic Assessment	EG0002 affected32 at risk EG0010 affected29 at risk EG0020 affected3 at risk
Fibrin D dimer increased	Investigations	MedDRA 19.0	Systematic Assessment	EG0002 affected32 at risk EG0010 affected29 at risk EG0020 affected3 at risk
Lymphocyte count increased	Investigations	MedDRA 19.0	Systematic Assessment	EG0001 affected32 at risk EG0010 affected29 at risk EG0021 affected3 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA 19.0	Systematic Assessment	EG00010 affected32 at risk EG0018 affected29 at risk EG0021 affected3 at risk
Hypoalbuminaemia	Metabolism and nutrition disorders	MedDRA 19.0	Systematic Assessment	EG0008 affected32 at risk EG0013 affected29 at risk EG0020 affected3 at risk
Hyponatraemia	Metabolism and nutrition disorders	MedDRA 19.0	Systematic Assessment	EG0008 affected32 at risk EG0012 affected29 at risk EG0020 affected3 at risk
Hypokalaemia	Metabolism and nutrition disorders	MedDRA 19.0	Systematic Assessment	EG0002 affected32 at risk EG0011 affected29 at risk EG0021 affected3 at risk
Fluid overload	Metabolism and nutrition disorders	MedDRA 19.0	Systematic Assessment	EG0003 affected32 at risk EG0011 affected29 at risk EG0020 affected3 at risk
Hypermagnesaemia	Metabolism and nutrition disorders	MedDRA 19.0	Systematic Assessment	EG0003 affected32 at risk EG0011 affected29 at risk EG0020 affected3 at risk
Hypocalcaemia	Metabolism and nutrition disorders	MedDRA 19.0	Systematic Assessment	EG0003 affected32 at risk EG0011 affected29 at risk EG0020 affected3 at risk
Hypomagnesaemia	Metabolism and nutrition disorders	MedDRA 19.0	Systematic Assessment	EG0004 affected32 at risk EG0010 affected29 at risk EG0020 affected3 at risk
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA 19.0	Systematic Assessment	EG0002 affected32 at risk EG0011 affected29 at risk EG0021 affected3 at risk
Hyperkalaemia	Metabolism and nutrition disorders	MedDRA 19.0	Systematic Assessment	EG0002 affected32 at risk EG0015 affected29 at risk EG0020 affected3 at risk
Hypophosphataemia	Metabolism and nutrition disorders	MedDRA 19.0	Systematic Assessment	EG0003 affected32 at risk EG0010 affected29 at risk EG0021 affected3 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA 19.0	Systematic Assessment	EG0002 affected32 at risk EG0010 affected29 at risk EG0020 affected3 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 19.0	Systematic Assessment	EG0006 affected32 at risk EG0016 affected29 at risk EG0020 affected3 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 19.0	Systematic Assessment	EG0002 affected32 at risk EG0013 affected29 at risk EG0020 affected3 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 19.0	Systematic Assessment	EG0003 affected32 at risk EG0011 affected29 at risk EG0020 affected3 at risk
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	MedDRA 19.0	Systematic Assessment	EG0003 affected32 at risk EG0011 affected29 at risk EG0020 affected3 at risk
Bone pain	Musculoskeletal and connective tissue disorders	MedDRA 19.0	Systematic Assessment	EG0002 affected32 at risk EG0011 affected29 at risk EG0020 affected3 at risk
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA 19.0	Systematic Assessment	EG0003 affected32 at risk EG0010 affected29 at risk EG0020 affected3 at risk
Neck pain	Musculoskeletal and connective tissue disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected32 at risk EG0012 affected29 at risk EG0020 affected3 at risk
Osteoarthritis	Musculoskeletal and connective tissue disorders	MedDRA 19.0	Systematic Assessment	EG0002 affected32 at risk EG0011 affected29 at risk EG0020 affected3 at risk
Musculoskeletal stiffness	Musculoskeletal and connective tissue disorders	MedDRA 19.0	Systematic Assessment	EG0000 affected32 at risk EG0010 affected29 at risk EG0021 affected3 at risk
Keratoacanthoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 19.0	Systematic Assessment	EG0002 affected32 at risk EG0010 affected29 at risk EG0020 affected3 at risk
Dizziness	Nervous system disorders	MedDRA 19.0	Systematic Assessment	EG0006 affected32 at risk EG0014 affected29 at risk EG0020 affected3 at risk
Headache	Nervous system disorders	MedDRA 19.0	Systematic Assessment	EG0004 affected32 at risk EG0013 affected29 at risk EG0021 affected3 at risk
Dysgeusia	Nervous system disorders	MedDRA 19.0	Systematic Assessment	EG0003 affected32 at risk EG0012 affected29 at risk EG0020 affected3 at risk
Tremor	Nervous system disorders	MedDRA 19.0	Systematic Assessment	EG0002 affected32 at risk EG0011 affected29 at risk EG0020 affected3 at risk
Memory impairment	Nervous system disorders	MedDRA 19.0	Systematic Assessment	EG0002 affected32 at risk EG0010 affected29 at risk EG0020 affected3 at risk
Neuropathy peripheral	Nervous system disorders	MedDRA 19.0	Systematic Assessment	EG0002 affected32 at risk EG0010 affected29 at risk EG0020 affected3 at risk
Paraesthesia	Nervous system disorders	MedDRA 19.0	Systematic Assessment	EG0002 affected32 at risk EG0010 affected29 at risk EG0020 affected3 at risk
Amnesia	Nervous system disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected32 at risk EG0010 affected29 at risk EG0021 affected3 at risk
Sinus headache	Nervous system disorders	MedDRA 19.0	Systematic Assessment	EG0000 affected32 at risk EG0012 affected29 at risk EG0020 affected3 at risk
Thrombosis in device	Product Issues	MedDRA 19.0	Systematic Assessment	EG0002 affected32 at risk EG0013 affected29 at risk EG0020 affected3 at risk
Insomnia	Psychiatric disorders	MedDRA 19.0	Systematic Assessment	EG0008 affected32 at risk EG0014 affected29 at risk EG0020 affected3 at risk
Anxiety	Psychiatric disorders	MedDRA 19.0	Systematic Assessment	EG0004 affected32 at risk EG0012 affected29 at risk EG0020 affected3 at risk
Depression	Psychiatric disorders	MedDRA 19.0	Systematic Assessment	EG0003 affected32 at risk EG0011 affected29 at risk EG0020 affected3 at risk
Delirium	Psychiatric disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected32 at risk EG0012 affected29 at risk EG0020 affected3 at risk
Confusional state	Psychiatric disorders	MedDRA 19.0	Systematic Assessment	EG0000 affected32 at risk EG0012 affected29 at risk EG0020 affected3 at risk
Hallucination	Psychiatric disorders	MedDRA 19.0	Systematic Assessment	EG0002 affected32 at risk EG0010 affected29 at risk EG0020 affected3 at risk
Acute kidney injury	Renal and urinary disorders	MedDRA 19.0	Systematic Assessment	EG0002 affected32 at risk EG0013 affected29 at risk EG0020 affected3 at risk
Haematuria	Renal and urinary disorders	MedDRA 19.0	Systematic Assessment	EG0002 affected32 at risk EG0011 affected29 at risk EG0020 affected3 at risk
Urinary incontinence	Renal and urinary disorders	MedDRA 19.0	Systematic Assessment	EG0002 affected32 at risk EG0011 affected29 at risk EG0020 affected3 at risk
Dysuria	Renal and urinary disorders	MedDRA 19.0	Systematic Assessment	EG0000 affected32 at risk EG0012 affected29 at risk EG0020 affected3 at risk
Nocturia	Renal and urinary disorders	MedDRA 19.0	Systematic Assessment	EG0002 affected32 at risk EG0010 affected29 at risk EG0021 affected3 at risk
Urinary retention	Renal and urinary disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected32 at risk EG0010 affected29 at risk EG0021 affected3 at risk
Vaginal haemorrhage	Reproductive system and breast disorders	MedDRA 19.0	Systematic Assessment	EG0000 affected32 at risk EG0012 affected29 at risk EG0020 affected3 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 19.0	Systematic Assessment	EG0007 affected32 at risk EG0013 affected29 at risk EG0021 affected3 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 19.0	Systematic Assessment	EG0004 affected32 at risk EG0013 affected29 at risk EG0020 affected3 at risk
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA 19.0	Systematic Assessment	EG0005 affected32 at risk EG0012 affected29 at risk EG0020 affected3 at risk
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA 19.0	Systematic Assessment	EG0004 affected32 at risk EG0011 affected29 at risk EG0020 affected3 at risk
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA 19.0	Systematic Assessment	EG0002 affected32 at risk EG0013 affected29 at risk EG0020 affected3 at risk
Nasal congestion	Respiratory, thoracic and mediastinal disorders	MedDRA 19.0	Systematic Assessment	EG0002 affected32 at risk EG0012 affected29 at risk EG0020 affected3 at risk
Rales	Respiratory, thoracic and mediastinal disorders	MedDRA 19.0	Systematic Assessment	EG0002 affected32 at risk EG0012 affected29 at risk EG0020 affected3 at risk
Hypoxia	Respiratory, thoracic and mediastinal disorders	MedDRA 19.0	Systematic Assessment	EG0002 affected32 at risk EG0011 affected29 at risk EG0020 affected3 at risk
Lung infiltration	Respiratory, thoracic and mediastinal disorders	MedDRA 19.0	Systematic Assessment	EG0000 affected32 at risk EG0012 affected29 at risk EG0020 affected3 at risk
Pleuritic pain	Respiratory, thoracic and mediastinal disorders	MedDRA 19.0	Systematic Assessment	EG0000 affected32 at risk EG0012 affected29 at risk EG0020 affected3 at risk
Pulmonary oedema	Respiratory, thoracic and mediastinal disorders	MedDRA 19.0	Systematic Assessment	EG0002 affected32 at risk EG0010 affected29 at risk EG0020 affected3 at risk
Erythema	Skin and subcutaneous tissue disorders	MedDRA 19.0	Systematic Assessment	EG0000 affected32 at risk EG0014 affected29 at risk EG0020 affected3 at risk
Night sweats	Skin and subcutaneous tissue disorders	MedDRA 19.0	Systematic Assessment	EG0003 affected32 at risk EG0011 affected29 at risk EG0020 affected3 at risk
Pruritus	Skin and subcutaneous tissue disorders	MedDRA 19.0	Systematic Assessment	EG0004 affected32 at risk EG0010 affected29 at risk EG0020 affected3 at risk
Rash maculo-papular	Skin and subcutaneous tissue disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected32 at risk EG0013 affected29 at risk EG0020 affected3 at risk
Hyperkeratosis	Skin and subcutaneous tissue disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected32 at risk EG0012 affected29 at risk EG0020 affected3 at risk
Actinic keratosis	Skin and subcutaneous tissue disorders	MedDRA 19.0	Systematic Assessment	EG0000 affected32 at risk EG0012 affected29 at risk EG0020 affected3 at risk
Petechiae	Skin and subcutaneous tissue disorders	MedDRA 19.0	Systematic Assessment	EG0002 affected32 at risk EG0010 affected29 at risk EG0020 affected3 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA 19.0	Systematic Assessment	EG0002 affected32 at risk EG0010 affected29 at risk EG0020 affected3 at risk
Hypotension	Vascular disorders	MedDRA 19.0	Systematic Assessment	EG0002 affected32 at risk EG0016 affected29 at risk EG0020 affected3 at risk
Deep vein thrombosis	Vascular disorders	MedDRA 19.0	Systematic Assessment	EG0002 affected32 at risk EG0011 affected29 at risk EG0020 affected3 at risk
Hypertension	Vascular disorders	MedDRA 19.0	Systematic Assessment	EG0003 affected32 at risk EG0010 affected29 at risk EG0020 affected3 at risk
Phlebitis	Vascular disorders	MedDRA 19.0	Systematic Assessment	EG0002 affected32 at risk EG0010 affected29 at risk EG0020 affected3 at risk

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

ID	Term
D001372	Aza Compounds
D009930	Organic Chemicals
D003562	Cytidine
D011741	Pyrimidine Nucleosides
D011743	Pyrimidines
D006573	Heterocyclic Compounds, 1-Ring
D006571	Heterocyclic Compounds
D009705	Nucleosides
D009706	Nucleic Acids, Nucleotides, and Nucleosides
D012263	Ribonucleosides

ID	Title	Description
BG000	MLN4924 20 mg/m^2 + Azacitidine 75 mg/m^2 Intravenous	MLN4924 20 mg/m^2, infusion, intravenously, once on Days 1, 3, and 5 in combination with azacitidine 75 mg/m^2, infusion, intravenously, once on Days 1 through 5, 8 and 9 before administration of MLN4924 in a 28-day treatment cycle up to symptomatic deterioration or progressive disease (PD), or until treatment was discontinued for another reason (up to Cycle 53).
BG001	MLN4924 20 mg/m^2 + Azacitidine 75 mg/m^2 Subcutaneous	MLN4924 20 mg/m^2, infusion, intravenously, once on Days 1, 3, and 5 in combination with azacitidine 75 mg/m^2, infusion, subcutaneously, once on Days 1 through 5, 8 and 9 before administration of MLN4924 in a 28-day treatment cycle up to symptomatic deterioration or PD, or until treatment was discontinued for another reason (up to Cycle 53).
BG002	MLN4924 30 mg/m^2 + Azacitidine 75 mg/m^2 Intravenous	MLN4924 30 mg/m^2, infusion, intravenously, once on Days 1, 3, and 5 in combination with azacitidine 75 mg/m^2, infusion, intravenously, once on Days 1 through 5, 8 and 9 before administration of MLN4924 in a 28-day treatment cycle up to symptomatic deterioration or PD, or until treatment was discontinued for another reason (up to Cycle 53).
BG003	Total	Total of all reporting groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	MLN4924 20 mg/m^2 + Azacitidine 75 mg/m^2 Intravenous	MLN4924 20 mg/m^2, infusion, intravenously, once on Days 1, 3, and 5 in combination with azacitidine 75 mg/m^2, infusion, intravenously, once on Days 1 through 5, 8 and 9 before administration of MLN4924 in a 28-day treatment cycle up to symptomatic deterioration or progressive disease (PD), or until treatment was discontinued for another reason (up to Cycle 53).	29	32	21	32	32	32
EG001	MLN4924 20 mg/m^2 + Azacitidine 75 mg/m^2 Subcutaneous	MLN4924 20 mg/m^2, infusion, intravenously, once on Days 1, 3, and 5 in combination with azacitidine 75 mg/m^2, infusion, subcutaneously, once on Days 1 through 5, 8 and 9 before administration of MLN4924 in a 28-day treatment cycle up to symptomatic deterioration or PD, or until treatment was discontinued for another reason (up to Cycle 53).	24	29	22	29	29	29
EG002	MLN4924 30 mg/m^2 + Azacitidine 75 mg/m^2 Intravenous	MLN4924 30 mg/m^2, infusion, intravenously, once on Days 1, 3, and 5 in combination with azacitidine 75 mg/m^2, infusion, intravenously, once on Days 1 through 5, 8 and 9 before administration of MLN4924 in a 28-day treatment cycle up to symptomatic deterioration or PD, or until treatment was discontinued for another reason (up to Cycle 53).	3	3	3	3	3	3