A Study of Pevonedistat in Adult East Asian Participants | NCT02782468

NCT02782468

ID	Type	Description	Link
U1111-1166-8630	Other Identifier	WHO

Status Module

Sponsor/Collaborators Module

Oversight Module

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Arm 1, Cohort 1: Pevonedistat 25 mg/m^2	Experimental	Pevonedistat, 25 milligram per square meter (mg/m^2), 60-minute infusion, intravenously, on Days 1, 3 and 5, followed by a rest period of 16 days, in 21-day treatment cycles.	Drug: Pevonedistat 25 mg/m^2
Arm 1, Cohort 2: Pevonedistat 44 mg/m^2	Experimental	Pevonedistat, 44 mg/m^2, 60-minute infusion, intravenously, on Days 1, 3, and 5, followed by a rest period of 16 days, in 21-day treatment cycles.	Drug: Pevonedistat 44 mg/m^2
Arm 2, Cohort 1: Pevonedistat 10 mg/m^2+ Azacitidine 75 mg/m^2	Experimental	Pevonedistat 10 mg/m^2, 60-minute infusion, intravenously, on Days 1, 3, and 5 and azacitidine 75 mg/m^2, on Days 1 to 5, and Days 8 and 9, intravenously or subcutaneously, followed by a rest period of 19 days, in 28-day treatment cycles.	Drug: Pevonedistat 10 mg/m^2 Drug: Azacitidine 75 mg/m^2
Arm 2, Cohort 2: Pevonedistat 20 mg/m^2+ Azacitidine 75 mg/m^2	Experimental	Pevonedistat 20 mg/m^2, 60-minute infusion, intravenously, on Days 1, 3, and 5 and azacitidine 75 mg/m^2, on Days 1 to 5, and Days 8 and 9, intravenously or subcutaneously, followed by a rest period of 19 days, in 28-day treatment cycles.	Drug: Pevonedistat 20 mg/m^2 Drug: Azacitidine 75 mg/m^2

Name	Type	Description	Arm Group Labels	Other Names
Pevonedistat 25 mg/m^2	Drug	Pevonedistat 25 mg/m^2 intravenous infusion.	Arm 1, Cohort 1: Pevonedistat 25 mg/m^2

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)		From first dose through 30 days after the last dose of study drug: single agent arms (up to Cycle 19 [up to Day 429]) (Cycle=21 days); combination arms (up to Cycle 65 [up to Day 1850]) (Cycle=28 days)
Number of Participants With Dose Limiting Toxicities (DLTs) Based on National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.03 During Cycle 1	DLT: Any of following events considered possibly related to study drug(s) by investigator: Grade (G) 3 or greater nausea and/or emesis despite use of optimal antiemetic prophylaxis; G3 diarrhea occurred despite maximal supportive therapy; G3 arthralgia/myalgia despite use of optimal analgesia; G3 nonhematologic toxicity with exceptions: 1) Brief fatigue, 2) hypophosphatemia; Persistent elevations of transaminases/bilirubin above G2 beyond 2 days between doses; Other study drug-related nonhematologic toxicities G2 or greater, required a dose reduction/discontinuation of pevonedistat. G3 or greater hematologic toxicities, including G3 or 4 febrile neutropenia, considered DLTs if: A delay in initiation of Cycle 2 due to lack of adequate recovery from treatment-related toxicity: 1) Of more than (>) 4 weeks due to hematologic toxicity believed not related to leukemic infiltration. Bone marrow (BM) evaluation may have been required. 2) Of >2 weeks due to nonhematologic toxicities.	Cycle 1 (Cycle length = 21 days [single agent arms]; 28 days [combination arms])
Number of Participants With Clinically Significant Abnormal Laboratory Values		Baseline up to Cycle 19 (up to Day 399) in single agent arms (Cycle=21days) and Cycle 65 (up to Day 1820) in combination arms (Cycle=28 days)
Cmax: Maximum Observed Plasma Concentration for Pevonedistat When Administered Alone and in Combination With Azacitidine on Cycle 1 Day 1		Cycle 1 Day 1: pre-infusion and at multiple time points (up to 48 hours) post-infusion (Cycle length = 21 days [single agent arms]; 28 days [combination arms])

Secondary Outcomes

Measure	Description	Time Frame
Overall Response Rate (ORR) for Participants With AML	ORR for AML was defined as the percentage of participants with a complete remission (CR), CR with incomplete blood count recovery (CRi), or partial remission (PR) based on Modified International Working Group (IWG) Response Criteria for AML. CR was defined as participant achieved the morphologic leukemia-free state and had an absolute neutrophil count (ANC) of more than 1,000 per microliter (/mcL) and platelets of greater than or equal to (>=) 100,000/mcL. A morphologic leukemia-free state requires less than (<) 5 percent (%) blasts in an aspirate sample with marrow spicules and with a count of at least 200 nucleated cells. CRi was, after chemotherapy, some participants who fulfilled all of the criteria for CR except for residual neutropenia (<1,000/mcL) or thrombocytopenia (<100,000/mcL). PR designation required all the hematologic values for a CR but with a decrease of at least 50% in the percentage of blasts to between 5% and 25% in the bone marrow aspirate.

Eligibility Module

Eligibility Criteria

Inclusion Criteria include, in part:

East Asian patients aged 18 years or older (or minimum age of legal consent consistent with local regulations) when written study informed consent is obtained must meet 1 of the following diagnosis criteria for either the Single-Agent Arm or the Combination Arm (additional restrictions apply to the Single Agent Arm):

a. Are male and female participants with WHO-defined AML, including leukemia secondary to prior chemotherapy or resulting from an antecedent hematologic disorder, who have failed to achieve CR or who have relapsed after prior therapy (R/R) and are not candidates for potentially curative treatment, or ii. Are male and female participants aged 60 years or older with previously untreated AML who have bone marrow blasts <30% and who are not candidates for standard induction chemotherapy, or iii. Are male and female participants with WHO-defined MDS that meets the IPSS-R criteria for the very high, high, or intermediate risk group, for whom standard curative, life-prolonging treatment does not exist or is no longer effective (R/R), or iv. Are male and female participants with previously untreated MDS that meets the IPSS-R criteria for the very high, high, or intermediate risk group, or vi. Are male and female participants with WHO-defined CMML-2 or CMML-1 that meets the IPSS-R criteria for the very high, high, or intermediate risk group CMML-1 participants must have bone marrow blasts >=5%
Has Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
Able to undergo bone marrow aspiration and biopsy at Screening.

Exclusion Criteria include, in part:

Acute promyelocytic leukemia (as diagnosed by morphologic examination of bone marrow, by fluorescent in situ hybridization or cytogenetics [t (15:17)] of peripheral blood or bone marrow, or by other accepted analysis) or AML associated with t (9;22) karyotypes or molecular.
More than 3 prior lines of therapy (Combination Arm only).
Prior therapy with hypomethylating agents (example, azacitidine, decitabine). (Combination Arm only).
Is eligible for a hematopoietic stem cell transplant.
Is a female participant who is lactating and breastfeeding or who have a positive serum pregnancy test during the screening period or a positive urine pregnancy test on Day 1 before first dose of study drug.
Had treatment with any investigational products within 14 days before the first dose of any study drug.
Has known hypersensitivity to azacitidine or mannitol (Combination Arm only).
Has known central nervous system involvement.
Had systemic antineoplastic therapy or radiotherapy within 14 days before the first dose of any study drug, except for hydroxyurea.

Contacts/Locations Module

Name	Affiliation	Role
Study Director	Takeda	Study Director

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
35545778	Derived	Handa H, Cheong JW, Onishi Y, Iida H, Kobayashi Y, Kim HJ, Chiou TJ, Izutsu K, Tsukurov O, Zhou X, Faessel H, Yuan Y, Sedarati F, Faller DV, Kimura A, Wu SJ. Pevonedistat in East Asian patients with acute myeloid leukemia or myelodysplastic syndromes: a phase 1/1b study to evaluate safety, pharmacokinetics and activity as a single agent and in combination with azacitidine. J Hematol Oncol. 2022 May 11;15(1):56. doi: 10.1186/s13045-022-01264-w.

IPD Sharing Statement Module

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Single Agent Arm: Pevonedistat 25 mg/m^2	Pevonedistat 25 milligram per square meter (mg/m^2), infusion, intravenously, on Days 1, 3 and 5, followed by a rest period of 16 days, in each 21-day treatment cycle until disease progression or symptomatic deterioration.
FG001	Single Agent Arm: Pevonedistat 44 mg/m^2

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

No data available

No data is available for this block.

Document Section

Large Document Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Jun 23, 2017	Jan 12, 2023

Derived Section

Miscellaneous Info Module

Submission Tracking

No data available

No data is available for this block.

Condition Browse Module

Intervention Browse Module

Masking Info

Safety population was defined as all enrolled participants who received at least 1 dose of any study drug, pevonedistat or azacitidine.

Arm/Group Information

ID	Title	Description
BG000	Single Agent Arm: Pevonedistat 25 mg/m^2	Pevonedistat 25 mg/m^2, infusion, intravenously, on Days 1, 3 and 5, followed by a rest period of 16 days, in each 21-day treatment cycle until disease progression or symptomatic deterioration.
BG001	Single Agent Arm: Pevonedistat 44 mg/m^2	Pevonedistat 44 mg/m^2, infusion, intravenously, on Days 1, 3, and 5, followed by a rest period of 16 days, in each 21-day treatment cycle until disease progression or symptomatic deterioration.
BG002	Combination Arm: Pevonedistat 10 mg/m^2+ Azacitidine 75 mg/m^2	Pevonedistat 10 mg/m^2, infusion, intravenously, on Days 1, 3, and 5 along with azacitidine 75 mg/m^2, injection, intravenously in Cycle 1 and intravenously or subcutaneously from Cycle 2 onwards, on Days 1 to 5, and Days 8 and 9, followed by a rest period of 19 days, in each 28-day treatment cycle until disease progression or symptomatic deterioration.
BG003	Combination Arm: Pevonedistat 20 mg/m^2+ Azacitidine 75 mg/m^2	Pevonedistat 20 mg/m^2, infusion, intravenously, on Days 1, 3, and 5 along with azacitidine 75 mg/m^2, injection, intravenously in Cycle 1 and intravenously or subcutaneously from Cycle 2 onwards, on Days 1 to 5, and Days 8 and 9, followed by a rest period of 19 days, in each 28-day treatment cycle until disease progression or symptomatic deterioration.
BG004	Total	Total of all reporting groups

Units	Counts
Participants	BG0003 BG0017 BG0023 BG00310 BG00423

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	BG00078.0± 5.20 BG00169.0± 11.27 BG00265.0± 9.54 BG003

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG0001 BG0010 BG002

Ethnicity (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Hispanic or Latino	BG0000 BG0010 BG002

Race (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
American Indian or Alaska Native	BG0000 BG0010 BG002

Region of Enrollment

Count of Participants

Participants

Title

Denominators

Categories

Japan

Title	Measurements
	BG0002 BG0012 BG002

Body Surface Area (BSA)

Mean

Standard Deviation

square meter (m^2)

Title

Denominators

Categories

Title	Measurements
	BG0001.5± 0.26 BG0011.7± 0.21 BG002

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 Reporting One or More Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

Safety population was defined as all enrolled participants who received at least 1 dose of any study drug, pevonedistat or azacitidine.

Posted

Count of Participants

Participants

From first dose through 30 days after the last dose of study drug: single agent arms (up to Cycle 19 [up to Day 429]) (Cycle=21 days); combination arms (up to Cycle 65 [up to Day 1850]) (Cycle=28 days)

ID	Title	Description
OG000	Single Agent Arm: Pevonedistat 25 mg/m^2	Pevonedistat 25 mg/m^2, infusion, intravenously, on Days 1, 3 and 5, followed by a rest period of 16 days, in each 21-day treatment cycle until disease progression or symptomatic deterioration.
OG001	Single Agent Arm: Pevonedistat 44 mg/m^2	Pevonedistat 44 mg/m^2, infusion, intravenously, on Days 1, 3, and 5, followed by a rest period of 16 days, in each 21-day treatment cycle until disease progression or symptomatic deterioration.
OG002	Combination Arm: Pevonedistat 10 mg/m^2+ Azacitidine 75 mg/m^2	Pevonedistat 10 mg/m^2, infusion, intravenously, on Days 1, 3, and 5 along with azacitidine 75 mg/m^2, injection, intravenously in Cycle 1 and intravenously or subcutaneously from Cycle 2 onwards, on Days 1 to 5, and Days 8 and 9, followed by a rest period of 19 days, in each 28-day treatment cycle until disease progression or symptomatic deterioration.
OG003	Combination Arm: Pevonedistat 20 mg/m^2+ Azacitidine 75 mg/m^2	Pevonedistat 20 mg/m^2, infusion, intravenously, on Days 1, 3, and 5 along with azacitidine 75 mg/m^2, injection, intravenously in Cycle 1 and intravenously or subcutaneously from Cycle 2 onwards, on Days 1 to 5, and Days 8 and 9, followed by a rest period of 19 days, in each 28-day treatment cycle until disease progression or symptomatic deterioration.

Units	Counts
Participants	OG0003 OG0017 OG0023 OG003

Title

Denominators

Categories

TEAEs

Title	Measurements
	OG0003 OG0017 OG0023 OG003

Primary

Number of Participants With Dose Limiting Toxicities (DLTs) Based on National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.03 During Cycle 1

DLT: Any of following events considered possibly related to study drug(s) by investigator: Grade (G) 3 or greater nausea and/or emesis despite use of optimal antiemetic prophylaxis; G3 diarrhea occurred despite maximal supportive therapy; G3 arthralgia/myalgia despite use of optimal analgesia; G3 nonhematologic toxicity with exceptions: 1) Brief fatigue, 2) hypophosphatemia; Persistent elevations of transaminases/bilirubin above G2 beyond 2 days between doses; Other study drug-related nonhematologic toxicities G2 or greater, required a dose reduction/discontinuation of pevonedistat. G3 or greater hematologic toxicities, including G3 or 4 febrile neutropenia, considered DLTs if: A delay in initiation of Cycle 2 due to lack of adequate recovery from treatment-related toxicity: 1) Of more than (>) 4 weeks due to hematologic toxicity believed not related to leukemic infiltration. Bone marrow (BM) evaluation may have been required. 2) Of >2 weeks due to nonhematologic toxicities.

The DLT evaluable population was defined as all participants who either experienced DLT during Cycle 1 or received all scheduled doses of study drug during Cycle 1 without DLT.

Posted

Count of Participants

Participants

Cycle 1 (Cycle length = 21 days [single agent arms]; 28 days [combination arms])

ID	Title	Description
OG000	Single Agent Arm: Pevonedistat 25 mg/m^2	Pevonedistat 25 mg/m^2, infusion, intravenously, on Days 1, 3 and 5, followed by a rest period of 16 days, in each 21-day treatment cycle until disease progression or symptomatic deterioration.

Primary

Number of Participants With Clinically Significant Abnormal Laboratory Values

Safety population was defined as all enrolled participants who received at least 1 dose of any study drug, pevonedistat or azacitidine.

Posted

Count of Participants

Participants

Baseline up to Cycle 19 (up to Day 399) in single agent arms (Cycle=21days) and Cycle 65 (up to Day 1820) in combination arms (Cycle=28 days)

ID	Title	Description
OG000	Single Agent Arm: Pevonedistat 25 mg/m^2	Pevonedistat 25 mg/m^2, infusion, intravenously, on Days 1, 3 and 5, followed by a rest period of 16 days, in each 21-day treatment cycle until disease progression or symptomatic deterioration.
OG001	Single Agent Arm: Pevonedistat 44 mg/m^2	Pevonedistat 44 mg/m^2, infusion, intravenously, on Days 1, 3, and 5, followed by a rest period of 16 days, in each 21-day treatment cycle until disease progression or symptomatic deterioration.
OG002	Combination Arm: Pevonedistat 10 mg/m^2+ Azacitidine 75 mg/m^2	Pevonedistat 10 mg/m^2, infusion, intravenously, on Days 1, 3, and 5 along with azacitidine 75 mg/m^2, injection, intravenously in Cycle 1 and intravenously or subcutaneously from Cycle 2 onwards, on Days 1 to 5, and Days 8 and 9, followed by a rest period of 19 days, in each 28-day treatment cycle until disease progression or symptomatic deterioration.

Primary

Cmax: Maximum Observed Plasma Concentration for Pevonedistat When Administered Alone and in Combination With Azacitidine on Cycle 1 Day 1

Pharmacokinetic (PK) evaluable population was defined as all enrolled participants who had sufficient dosing in Cycle 1 and pevonedistat concentration-time data to reliably estimate PK parameters by noncompartmental analysis methods and who had not received any excluded concomitant medications per the protocol.

Posted

Geometric Mean

Geometric Coefficient of Variation

nanogram per milliliter (ng/mL)

Cycle 1 Day 1: pre-infusion and at multiple time points (up to 48 hours) post-infusion (Cycle length = 21 days [single agent arms]; 28 days [combination arms])

ID	Title	Description
OG000	Single Agent Arm: Pevonedistat 25 mg/m^2	Pevonedistat 25 mg/m^2, infusion, intravenously, on Days 1, 3 and 5, followed by a rest period of 16 days, in each 21-day treatment cycle until disease progression or symptomatic deterioration.
OG001	Single Agent Arm: Pevonedistat 44 mg/m^2	Pevonedistat 44 mg/m^2, infusion, intravenously, on Days 1, 3, and 5, followed by a rest period of 16 days, in each 21-day treatment cycle until disease progression or symptomatic deterioration.
OG002	Combination Arm: Pevonedistat 10 mg/m^2+ Azacitidine 75 mg/m^2

Primary

Cmax: Maximum Observed Plasma Concentration for Pevonedistat When Administered Alone and in Combination With Azacitidine on Cycle 1 Day 5

PK evaluable population was defined as all enrolled participants who had sufficient dosing in Cycle 1 and pevonedistat concentration-time data to reliably estimate PK parameters by noncompartmental analysis methods and who had not received any excluded concomitant medications per the protocol. Here, "overall number of participants analyzed" signifies those participants who were evaluable for this outcome measure.

Posted

Geometric Mean

Geometric Coefficient of Variation

ng/mL

Cycle 1 Day 5: pre-infusion and at multiple time points (up to 48 hours) post-infusion (Cycle length = 21 days [single agent arms]; 28 days [combination arms])

ID	Title	Description
OG000	Single Agent Arm: Pevonedistat 25 mg/m^2	Pevonedistat 25 mg/m^2, infusion, intravenously, on Days 1, 3 and 5, followed by a rest period of 16 days, in each 21-day treatment cycle until disease progression or symptomatic deterioration.
OG001	Single Agent Arm: Pevonedistat 44 mg/m^2	Pevonedistat 44 mg/m^2, infusion, intravenously, on Days 1, 3, and 5, followed by a rest period of 16 days, in each 21-day treatment cycle until disease progression or symptomatic deterioration.
OG002	Combination Arm: Pevonedistat 10 mg/m^2+ Azacitidine 75 mg/m^2

Primary

AUC(0-tau): Area Under the Plasma Concentration-time Curve From Time 0 to Time Tau Over the Dosing Interval for Pevonedistat When Administered Alone and in Combination With Azacitidine on Cycle 1 Day 5

Posted

Geometric Mean

Geometric Coefficient of Variation

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

Cycle 1 Day 5: pre-infusion and at multiple time points (up to 48 hours) post-infusion (Cycle length = 21 days [single agent arms]; 28 days [combination arms])

ID	Title	Description
OG000	Single Agent Arm: Pevonedistat 25 mg/m^2	Pevonedistat 25 mg/m^2, infusion, intravenously, on Days 1, 3 and 5, followed by a rest period of 16 days, in each 21-day treatment cycle until disease progression or symptomatic deterioration.
OG001	Single Agent Arm: Pevonedistat 44 mg/m^2	Pevonedistat 44 mg/m^2, infusion, intravenously, on Days 1, 3, and 5, followed by a rest period of 16 days, in each 21-day treatment cycle until disease progression or symptomatic deterioration.
OG002

Primary

CL: Total Clearance for Pevonedistat When Administered Alone and in Combination With Azacitidine on Cycle 1 Day 1

Posted

Geometric Mean

Geometric Coefficient of Variation

liter per hour

Cycle 1 Day 1: pre-infusion and at multiple time points (up to 48 hours) post-infusion (Cycle length = 21 days [single agent arms]; 28 days [combination arms])

ID	Title	Description
OG000	Single Agent Arm: Pevonedistat 25 mg/m^2	Pevonedistat 25 mg/m^2, infusion, intravenously, on Days 1, 3 and 5, followed by a rest period of 16 days, in each 21-day treatment cycle until disease progression or symptomatic deterioration.
OG001	Single Agent Arm: Pevonedistat 44 mg/m^2	Pevonedistat 44 mg/m^2, infusion, intravenously, on Days 1, 3, and 5, followed by a rest period of 16 days, in each 21-day treatment cycle until disease progression or symptomatic deterioration.
OG002	Combination Arm: Pevonedistat 10 mg/m^2+ Azacitidine 75 mg/m^2	Pevonedistat 10 mg/m^2, infusion, intravenously, on Days 1, 3, and 5 along with azacitidine 75 mg/m^2, injection, intravenously in Cycle 1 and intravenously or subcutaneously from Cycle 2 onwards, on Days 1 to 5, and Days 8 and 9, followed by a rest period of 19 days, in each 28-day treatment cycle until disease progression or symptomatic deterioration.

Primary

CL: Total Clearance for Pevonedistat When Administered Alone and in Combination With Azacitidine on Cycle 1 Day 5

Posted

Geometric Mean

Geometric Coefficient of Variation

liter per hour

Cycle 1 Day 5: pre-infusion and at multiple time points (up to 48 hours) post-infusion (Cycle length = 21 days [single agent arms]; 28 days [combination arms])

ID	Title	Description
OG000	Single Agent Arm: Pevonedistat 25 mg/m^2	Pevonedistat 25 mg/m^2, infusion, intravenously, on Days 1, 3 and 5, followed by a rest period of 16 days, in each 21-day treatment cycle until disease progression or symptomatic deterioration.
OG001	Single Agent Arm: Pevonedistat 44 mg/m^2	Pevonedistat 44 mg/m^2, infusion, intravenously, on Days 1, 3, and 5, followed by a rest period of 16 days, in each 21-day treatment cycle until disease progression or symptomatic deterioration.
OG002	Combination Arm: Pevonedistat 10 mg/m^2+ Azacitidine 75 mg/m^2

Secondary

Overall Response Rate (ORR) for Participants With AML

ORR for AML was defined as the percentage of participants with a complete remission (CR), CR with incomplete blood count recovery (CRi), or partial remission (PR) based on Modified International Working Group (IWG) Response Criteria for AML. CR was defined as participant achieved the morphologic leukemia-free state and had an absolute neutrophil count (ANC) of more than 1,000 per microliter (/mcL) and platelets of greater than or equal to (>=) 100,000/mcL. A morphologic leukemia-free state requires less than (<) 5 percent (%) blasts in an aspirate sample with marrow spicules and with a count of at least 200 nucleated cells. CRi was, after chemotherapy, some participants who fulfilled all of the criteria for CR except for residual neutropenia (<1,000/mcL) or thrombocytopenia (<100,000/mcL). PR designation required all the hematologic values for a CR but with a decrease of at least 50% in the percentage of blasts to between 5% and 25% in the bone marrow aspirate.

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. Here, "overall number of participants analyzed" signifies those participants who were evaluable for this outcome measure.

Posted

Number

percentage of participants

From first dose up to 30 days after last dose of study drug or before start of subsequent antineoplastic therapy, whichever comes earlier up to Cycle 19 (up to Day 429, single agent)(Cycle=21 days) and Cycle 65 (up to Day 1850, combination)(Cycle=28 days)

ID	Title	Description
OG000	Single Agent Arm: Pevonedistat 25 mg/m^2

Secondary

ORR for Participants With MDS

ORR for MDS: Percentage of participants with CR,PR or hematologic improvement(HI) based on IWG Response Criteria. CR: BM:<=5% myeloblasts with normal maturation of all cell lines; persistent dysplasia noted peripheral blood: hemoglobin (Hgb)>=11 gram per deciliter (g/dL),platelets>=100*10^9/L,neutrophils >=1.0*10^9/L, blasts 0%. PR:CR criteria if abnormal before treatment except: BM blasts decreased by >=50% from pretreatment but still>5%; cellularity, morphology not relevant. HI criteria: Erythroid response:Hgb up by >=1.5 g/dL; transfused RBC reduced by at least 4 red blood cell (RBC) transfusions/8 weeks comparatively last 8 weeks; Platelet response: Increase of >=30*10^9/L for participants starting with >20*10^9/L platelets; increase from <20*10^9/L to >20*10^9/L and by 100%; Neutrophil response: At least 100% and absolute increase >0.5*10^9/L; Progression/relapse after HI: Granulocytes/platelets decreased by 50% from maximum; Hgb reduced by >=1.5 g/dL; transfusion dependence.

Posted

Number

percentage of participants

ID	Title	Description
OG000	Single Agent Arm: Pevonedistat 25 mg/m^2

Secondary

Percentage of Participants With CR for Participants With AML

CR was defined as participant achieved the morphologic leukemia-free state and had an ANC of more than 1,000/mcL and platelets of >=100,000/mcL. A morphologic leukemia-free state requires <5% blasts in an aspirate sample with marrow spicules and with a count of at least 200 nucleated cells. CR assessment was based on IWG Response Criteria.

Posted

Number

percentage of participants

ID	Title	Description
OG000	Single Agent Arm: Pevonedistat 25 mg/m^2	Pevonedistat 25 mg/m^2, infusion, intravenously, on Days 1, 3 and 5, followed by a rest period of 16 days, in each 21-day treatment cycle until disease progression or symptomatic deterioration.
OG001	Single Agent Arm: Pevonedistat 44 mg/m^2	Pevonedistat 44 mg/m^2, infusion, intravenously, on Days 1, 3, and 5, followed by a rest period of 16 days, in each 21-day treatment cycle until disease progression or symptomatic deterioration.

Secondary

Percentage of Participants With CR for Participants With MDS

CR was defined as participant with bone marrow: less than or equal to (<=) 5% myeloblasts with normal maturation of all cell lines; persistent dysplasia was noted peripheral blood: Hgb >=11 g/dL, platelets >=100*10^9/L, neutrophils >=1.0*10^9 per liter (/L), blasts 0%. CR assessment was based on IWG Response Criteria.

Posted

Number

percentage of participants

ID	Title	Description
OG000	Single Agent Arm: Pevonedistat 25 mg/m^2	Pevonedistat 25 mg/m^2, infusion, intravenously, on Days 1, 3 and 5, followed by a rest period of 16 days, in each 21-day treatment cycle until disease progression or symptomatic deterioration.
OG001	Single Agent Arm: Pevonedistat 44 mg/m^2	Pevonedistat 44 mg/m^2, infusion, intravenously, on Days 1, 3, and 5, followed by a rest period of 16 days, in each 21-day treatment cycle until disease progression or symptomatic deterioration.

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	Single Agent Arm: Pevonedistat 25 mg/m^2	Pevonedistat 25 mg/m^2, infusion, intravenously, on Days 1, 3 and 5, followed by a rest period of 16 days, in each 21-day treatment cycle until disease progression or symptomatic deterioration.	1	3	2	3	3	3
EG001	Single Agent Arm: Pevonedistat 44 mg/m^2	Pevonedistat 44 mg/m^2, infusion, intravenously, on Days 1, 3, and 5, followed by a rest period of 16 days, in each 21-day treatment cycle until disease progression or symptomatic deterioration.	2	7	7	7	7	7
EG002	Combination Arm: Pevonedistat 10 mg/m^2 + Azacitidine 75 mg/m^2	Pevonedistat 10 mg/m^2, infusion, intravenously, on Days 1, 3, and 5 along with azacitidine 75 mg/m^2, injection, intravenously in Cycle 1 and intravenously or subcutaneously from Cycle 2 onwards, on Days 1 to 5, and Days 8 and 9, followed by a rest period of 19 days, in each 28-day treatment cycle until disease progression or symptomatic deterioration.	1	3	3	3	3	3
EG003	Combination Arm: Pevonedistat 20 mg/m^2 + Azacitidine 75 mg/m^2	Pevonedistat 20 mg/m^2, infusion, intravenously, on Days 1, 3, and 5 along with azacitidine 75 mg/m^2, injection, intravenously in Cycle 1 and intravenously or subcutaneously from Cycle 2 onwards, on Days 1 to 5, and Days 8 and 9, followed by a rest period of 19 days, in each 28-day treatment cycle until disease progression or symptomatic deterioration.	1	10	6	10	10	10

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Acute kidney injury	Renal and urinary disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected7 at risk EG0020 affected3 at risk EG0031 affected10 at risk
Acute myeloid leukaemia	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0011 affected7 at risk EG0020 affected3 at risk EG003
Anal abscess	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected7 at risk EG0020 affected3 at risk EG003
Arthritis bacterial	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected7 at risk EG0021 affected3 at risk EG003
Bacterial infection	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected7 at risk EG0020 affected3 at risk EG003
Bronchopulmonary aspergillosis	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0001 affected3 at risk EG0010 affected7 at risk EG0020 affected3 at risk EG003
Catheter site cellulitis	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected7 at risk EG0020 affected3 at risk EG003
Cellulitis	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected7 at risk EG0021 affected3 at risk EG003
Colitis	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected7 at risk EG0020 affected3 at risk EG003
Febrile neutropenia	Blood and lymphatic system disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0013 affected7 at risk EG0020 affected3 at risk EG003
Gastric ulcer	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected7 at risk EG0020 affected3 at risk EG003
Gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected7 at risk EG0020 affected3 at risk EG003
Humerus fracture	Injury, poisoning and procedural complications	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0011 affected7 at risk EG0020 affected3 at risk EG003
Lung neoplasm malignant	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected7 at risk EG0021 affected3 at risk EG003
Malignant peritoneal neoplasm	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected7 at risk EG0020 affected3 at risk EG003
Mesenteric panniculitis	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected7 at risk EG0020 affected3 at risk EG003
Neutrophil count decreased	Investigations	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected7 at risk EG0020 affected3 at risk EG003
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0011 affected7 at risk EG0020 affected3 at risk EG003
Pneumonia	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0001 affected3 at risk EG0015 affected7 at risk EG0022 affected3 at risk EG003
Pyrexia	General disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected7 at risk EG0020 affected3 at risk EG003
Septic shock	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected7 at risk EG0021 affected3 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected7 at risk EG0021 affected3 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Abdominal discomfort	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected7 at risk EG0020 affected3 at risk EG0031 affected10 at risk
Abdominal distension	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0012 affected7 at risk EG0021 affected3 at risk EG003
Abdominal pain	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected7 at risk EG0022 affected3 at risk EG003
Abdominal pain upper	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0011 affected7 at risk EG0021 affected3 at risk EG003
Acarodermatitis	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected7 at risk EG0021 affected3 at risk EG003
Acidosis	Metabolism and nutrition disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0011 affected7 at risk EG0020 affected3 at risk EG003
Acute febrile neutrophilic dermatosis	Skin and subcutaneous tissue disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected7 at risk EG0021 affected3 at risk EG003
Acute kidney injury	Renal and urinary disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0011 affected7 at risk EG0020 affected3 at risk EG003
Age-related macular degeneration	Eye disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected7 at risk EG0020 affected3 at risk EG003
Alanine aminotransferase increased	Investigations	MedDRA 23.0	Systematic Assessment	EG0001 affected3 at risk EG0010 affected7 at risk EG0022 affected3 at risk EG003
Allergic transfusion reaction	Injury, poisoning and procedural complications	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0011 affected7 at risk EG0020 affected3 at risk EG003
Anaemia	Blood and lymphatic system disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected7 at risk EG0022 affected3 at risk EG003
Anal abscess	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected7 at risk EG0020 affected3 at risk EG003
Anal haemorrhage	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0011 affected7 at risk EG0020 affected3 at risk EG003
Anal pruritus	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected7 at risk EG0021 affected3 at risk EG003
Angina pectoris	Cardiac disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected7 at risk EG0020 affected3 at risk EG003
Arterial fibrosis	Vascular disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0011 affected7 at risk EG0020 affected3 at risk EG003
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0012 affected7 at risk EG0021 affected3 at risk EG003
Arthritis bacterial	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected7 at risk EG0021 affected3 at risk EG003
Aspartate aminotransferase increased	Investigations	MedDRA 23.0	Systematic Assessment	EG0001 affected3 at risk EG0011 affected7 at risk EG0022 affected3 at risk EG003
Aspergillus infection	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected7 at risk EG0020 affected3 at risk EG003
Atrial fibrillation	Cardiac disorders	MedDRA 23.0	Systematic Assessment	EG0001 affected3 at risk EG0010 affected7 at risk EG0020 affected3 at risk EG003
Bacillus bacteraemia	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected7 at risk EG0020 affected3 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected7 at risk EG0023 affected3 at risk EG003
Bacteraemia	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected7 at risk EG0020 affected3 at risk EG003
Bacterial infection	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected7 at risk EG0020 affected3 at risk EG003
Bacterial sepsis	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0001 affected3 at risk EG0010 affected7 at risk EG0020 affected3 at risk EG003
Balanoposthitis	Reproductive system and breast disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0011 affected7 at risk EG0020 affected3 at risk EG003
Benign prostatic hyperplasia	Reproductive system and breast disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected7 at risk EG0020 affected3 at risk EG003
Bilirubin conjugated increased	Investigations	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected7 at risk EG0020 affected3 at risk EG003
Blood alkaline phosphatase increased	Investigations	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0011 affected7 at risk EG0020 affected3 at risk EG003
Blood bilirubin increased	Investigations	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected7 at risk EG0021 affected3 at risk EG003
Blood glucose decreased	Investigations	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected7 at risk EG0020 affected3 at risk EG003
Blood urea increased	Investigations	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected7 at risk EG0020 affected3 at risk EG003
Bone marrow failure	Blood and lymphatic system disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected7 at risk EG0021 affected3 at risk EG003
Bone pain	Musculoskeletal and connective tissue disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected7 at risk EG0021 affected3 at risk EG003
Bursitis	Musculoskeletal and connective tissue disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected7 at risk EG0021 affected3 at risk EG003
Cachexia	Metabolism and nutrition disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected7 at risk EG0021 affected3 at risk EG003
Catheter site cellulitis	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected7 at risk EG0020 affected3 at risk EG003
Catheter site erythema	General disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected7 at risk EG0020 affected3 at risk EG003
Catheter site extravasation	General disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected7 at risk EG0020 affected3 at risk EG003
Catheter site injury	General disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0011 affected7 at risk EG0020 affected3 at risk EG003
Catheter site pain	General disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected7 at risk EG0020 affected3 at risk EG003
Catheter site pruritus	General disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected7 at risk EG0020 affected3 at risk EG003
Catheter site swelling	General disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected7 at risk EG0020 affected3 at risk EG003
Cellulitis	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0011 affected7 at risk EG0021 affected3 at risk EG003
Conjunctival haemorrhage	Eye disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected7 at risk EG0021 affected3 at risk EG003
Conjunctival pallor	Eye disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected7 at risk EG0021 affected3 at risk EG003
Conjunctivitis	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected7 at risk EG0020 affected3 at risk EG003
Constipation	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0001 affected3 at risk EG0013 affected7 at risk EG0022 affected3 at risk EG003
Contusion	Injury, poisoning and procedural complications	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0011 affected7 at risk EG0021 affected3 at risk EG003
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0011 affected7 at risk EG0021 affected3 at risk EG003
Decreased appetite	Metabolism and nutrition disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected7 at risk EG0022 affected3 at risk EG003
Dental caries	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected7 at risk EG0020 affected3 at risk EG003
Dermatitis acneiform	Skin and subcutaneous tissue disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected7 at risk EG0021 affected3 at risk EG003
Dermatosis	Skin and subcutaneous tissue disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected7 at risk EG0021 affected3 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0001 affected3 at risk EG0012 affected7 at risk EG0020 affected3 at risk EG003
Disseminated intravascular coagulation	Blood and lymphatic system disorders	MedDRA 23.0	Systematic Assessment	EG0001 affected3 at risk EG0010 affected7 at risk EG0020 affected3 at risk EG003
Dizziness	Nervous system disorders	MedDRA 23.0	Systematic Assessment	EG0001 affected3 at risk EG0011 affected7 at risk EG0021 affected3 at risk EG003
Drug hypersensitivity	Immune system disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected7 at risk EG0020 affected3 at risk EG003
Dry eye	Eye disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected7 at risk EG0020 affected3 at risk EG003
Dry mouth	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0001 affected3 at risk EG0010 affected7 at risk EG0020 affected3 at risk EG003
Dry skin	Skin and subcutaneous tissue disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected7 at risk EG0020 affected3 at risk EG003
Dyspepsia	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected7 at risk EG0020 affected3 at risk EG003
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0012 affected7 at risk EG0021 affected3 at risk EG003
Dyspnoea exertional	Respiratory, thoracic and mediastinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected7 at risk EG0021 affected3 at risk EG003
Dysuria	Renal and urinary disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0011 affected7 at risk EG0020 affected3 at risk EG003
Ear pain	Ear and labyrinth disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0011 affected7 at risk EG0020 affected3 at risk EG003
Ecchymosis	Skin and subcutaneous tissue disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected7 at risk EG0021 affected3 at risk EG003
Eczema	Skin and subcutaneous tissue disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected7 at risk EG0021 affected3 at risk EG003
Enlarged uvula	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected7 at risk EG0020 affected3 at risk EG003
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0011 affected7 at risk EG0020 affected3 at risk EG003
Erythema	Skin and subcutaneous tissue disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected7 at risk EG0021 affected3 at risk EG003
Exfoliative rash	Skin and subcutaneous tissue disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected7 at risk EG0020 affected3 at risk EG003
Eye contusion	Injury, poisoning and procedural complications	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0011 affected7 at risk EG0021 affected3 at risk EG003
Facial bones fracture	Injury, poisoning and procedural complications	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0011 affected7 at risk EG0020 affected3 at risk EG003
Fall	Injury, poisoning and procedural complications	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0011 affected7 at risk EG0020 affected3 at risk EG003
Fatigue	General disorders	MedDRA 23.0	Systematic Assessment	EG0001 affected3 at risk EG0012 affected7 at risk EG0022 affected3 at risk EG003
Febrile neutropenia	Blood and lymphatic system disorders	MedDRA 23.0	Systematic Assessment	EG0002 affected3 at risk EG0014 affected7 at risk EG0020 affected3 at risk EG003
Flank pain	Musculoskeletal and connective tissue disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected7 at risk EG0021 affected3 at risk EG003
Folliculitis	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected7 at risk EG0021 affected3 at risk EG003
Gamma-glutamyltransferase increased	Investigations	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0011 affected7 at risk EG0020 affected3 at risk EG003
Gastric ulcer	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected7 at risk EG0020 affected3 at risk EG003
Gastritis	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected7 at risk EG0021 affected3 at risk EG003
Gastroenteritis	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected7 at risk EG0021 affected3 at risk EG003
Gingivitis	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected7 at risk EG0020 affected3 at risk EG003
Haematoma	Vascular disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected7 at risk EG0021 affected3 at risk EG003
Haematuria	Renal and urinary disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected7 at risk EG0021 affected3 at risk EG003
Haemophilus infection	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected7 at risk EG0021 affected3 at risk EG003
Haemorrhage	Vascular disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected7 at risk EG0021 affected3 at risk EG003
Haemorrhage intracranial	Nervous system disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0011 affected7 at risk EG0020 affected3 at risk EG003
Haemorrhoids	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected7 at risk EG0021 affected3 at risk EG003
Headache	Nervous system disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0011 affected7 at risk EG0020 affected3 at risk EG003
Hepatic cyst	Hepatobiliary disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected7 at risk EG0021 affected3 at risk EG003
Hepatic function abnormal	Hepatobiliary disorders	MedDRA 23.0	Systematic Assessment	EG0001 affected3 at risk EG0010 affected7 at risk EG0020 affected3 at risk EG003
Hepatitis B	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0001 affected3 at risk EG0010 affected7 at risk EG0020 affected3 at risk EG003
Herpes zoster	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0011 affected7 at risk EG0020 affected3 at risk EG003
Hiccups	Respiratory, thoracic and mediastinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected7 at risk EG0020 affected3 at risk EG003
Hyperbilirubinaemia	Hepatobiliary disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected7 at risk EG0020 affected3 at risk EG003
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0012 affected7 at risk EG0021 affected3 at risk EG003
Hyperkalaemia	Metabolism and nutrition disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected7 at risk EG0021 affected3 at risk EG003
Hyperkeratosis	Skin and subcutaneous tissue disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected7 at risk EG0020 affected3 at risk EG003
Hypermagnesaemia	Metabolism and nutrition disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected7 at risk EG0021 affected3 at risk EG003
Hypertension	Vascular disorders	MedDRA 23.0	Systematic Assessment	EG0001 affected3 at risk EG0011 affected7 at risk EG0020 affected3 at risk EG003
Hyperuricaemia	Metabolism and nutrition disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0011 affected7 at risk EG0020 affected3 at risk EG003
Hypoacusis	Ear and labyrinth disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected7 at risk EG0020 affected3 at risk EG003
Hypoaesthesia	Nervous system disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected7 at risk EG0020 affected3 at risk EG003
Hypoalbuminaemia	Metabolism and nutrition disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected7 at risk EG0021 affected3 at risk EG003
Hypocalcaemia	Metabolism and nutrition disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0011 affected7 at risk EG0021 affected3 at risk EG003
Hypokalaemia	Metabolism and nutrition disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0012 affected7 at risk EG0022 affected3 at risk EG003
Hypomagnesaemia	Metabolism and nutrition disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0011 affected7 at risk EG0022 affected3 at risk EG003
Hypophosphataemia	Metabolism and nutrition disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0013 affected7 at risk EG0020 affected3 at risk EG003
Hypotension	Vascular disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0012 affected7 at risk EG0020 affected3 at risk EG003
Hypoxia	Respiratory, thoracic and mediastinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected7 at risk EG0020 affected3 at risk EG003
Ileus	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0011 affected7 at risk EG0020 affected3 at risk EG003
Incision site pruritus	Injury, poisoning and procedural complications	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected7 at risk EG0021 affected3 at risk EG003
Influenza	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected7 at risk EG0020 affected3 at risk EG003
Infusion site extravasation	General disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected7 at risk EG0021 affected3 at risk EG003
Injection site reaction	General disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected7 at risk EG0022 affected3 at risk EG003
Insomnia	Psychiatric disorders	MedDRA 23.0	Systematic Assessment	EG0001 affected3 at risk EG0013 affected7 at risk EG0021 affected3 at risk EG003
Iron overload	Metabolism and nutrition disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected7 at risk EG0021 affected3 at risk EG003
Klebsiella bacteraemia	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected7 at risk EG0021 affected3 at risk EG003
Laryngeal inflammation	Respiratory, thoracic and mediastinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected7 at risk EG0021 affected3 at risk EG003
Laryngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0011 affected7 at risk EG0020 affected3 at risk EG003
Leukocytosis	Blood and lymphatic system disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0012 affected7 at risk EG0020 affected3 at risk EG003
Lip ulceration	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected7 at risk EG0020 affected3 at risk EG003
Liver abscess	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0011 affected7 at risk EG0020 affected3 at risk EG003
Localised oedema	General disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected7 at risk EG0020 affected3 at risk EG003
Lower gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0001 affected3 at risk EG0010 affected7 at risk EG0020 affected3 at risk EG003
Malaise	General disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0012 affected7 at risk EG0021 affected3 at risk EG003
Malignant peritoneal neoplasm	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected7 at risk EG0020 affected3 at risk EG003
Mouth haemorrhage	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0011 affected7 at risk EG0020 affected3 at risk EG003
Mouth ulceration	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected7 at risk EG0021 affected3 at risk EG003
Muscle atrophy	Musculoskeletal and connective tissue disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected7 at risk EG0021 affected3 at risk EG003
Musculoskeletal chest pain	Musculoskeletal and connective tissue disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0011 affected7 at risk EG0020 affected3 at risk EG003
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected7 at risk EG0021 affected3 at risk EG003
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0011 affected7 at risk EG0021 affected3 at risk EG003
Myocardial ischaemia	Cardiac disorders	MedDRA 23.0	Systematic Assessment	EG0001 affected3 at risk EG0010 affected7 at risk EG0020 affected3 at risk EG003
Myofascial pain syndrome	Musculoskeletal and connective tissue disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected7 at risk EG0021 affected3 at risk EG003
Nasal congestion	Respiratory, thoracic and mediastinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected7 at risk EG0020 affected3 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0001 affected3 at risk EG0013 affected7 at risk EG0021 affected3 at risk EG003
Neck pain	Musculoskeletal and connective tissue disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected7 at risk EG0021 affected3 at risk EG003
Neutropenia	Blood and lymphatic system disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected7 at risk EG0020 affected3 at risk EG003
Neutrophil count decreased	Investigations	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected7 at risk EG0021 affected3 at risk EG003
Oedema peripheral	General disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0011 affected7 at risk EG0021 affected3 at risk EG003
Oral candidiasis	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0011 affected7 at risk EG0020 affected3 at risk EG003
Oral herpes	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0011 affected7 at risk EG0020 affected3 at risk EG003
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0011 affected7 at risk EG0020 affected3 at risk EG003
Orthostatic hypotension	Vascular disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected7 at risk EG0021 affected3 at risk EG003
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 23.0	Systematic Assessment	EG0001 affected3 at risk EG0010 affected7 at risk EG0020 affected3 at risk EG003
Paraesthesia	Nervous system disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected7 at risk EG0020 affected3 at risk EG003
Pelvic pain	Reproductive system and breast disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected7 at risk EG0020 affected3 at risk EG003
Penis injury	Injury, poisoning and procedural complications	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0011 affected7 at risk EG0020 affected3 at risk EG003
Periarthritis	Musculoskeletal and connective tissue disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected7 at risk EG0020 affected3 at risk EG003
Periodontitis	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected7 at risk EG0021 affected3 at risk EG003
Peripheral swelling	General disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0012 affected7 at risk EG0020 affected3 at risk EG003
Peritonitis	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected7 at risk EG0020 affected3 at risk EG003
Petechiae	Skin and subcutaneous tissue disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0012 affected7 at risk EG0020 affected3 at risk EG003
Phlebitis	Vascular disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0011 affected7 at risk EG0021 affected3 at risk EG003
Platelet count decreased	Investigations	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0011 affected7 at risk EG0021 affected3 at risk EG003
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0012 affected7 at risk EG0020 affected3 at risk EG003
Pneumonia	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0013 affected7 at risk EG0020 affected3 at risk EG003
Pollakiuria	Renal and urinary disorders	MedDRA 23.0	Systematic Assessment	EG0001 affected3 at risk EG0010 affected7 at risk EG0020 affected3 at risk EG003
Presyncope	Nervous system disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0011 affected7 at risk EG0020 affected3 at risk EG003
Procedural pain	Injury, poisoning and procedural complications	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected7 at risk EG0021 affected3 at risk EG003
Productive cough	Respiratory, thoracic and mediastinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0011 affected7 at risk EG0021 affected3 at risk EG003
Prurigo	Skin and subcutaneous tissue disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected7 at risk EG0020 affected3 at risk EG003
Pruritus	Skin and subcutaneous tissue disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected7 at risk EG0022 affected3 at risk EG003
Psoriasis	Skin and subcutaneous tissue disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected7 at risk EG0021 affected3 at risk EG003
Pustule	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected7 at risk EG0021 affected3 at risk EG003
Pyrexia	General disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0011 affected7 at risk EG0021 affected3 at risk EG003
Rash	Skin and subcutaneous tissue disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected7 at risk EG0020 affected3 at risk EG003
Rash erythematous	Skin and subcutaneous tissue disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected7 at risk EG0021 affected3 at risk EG003
Rash macular	Skin and subcutaneous tissue disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected7 at risk EG0021 affected3 at risk EG003
Rash papular	Skin and subcutaneous tissue disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected7 at risk EG0022 affected3 at risk EG003
Rash pruritic	Skin and subcutaneous tissue disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected7 at risk EG0022 affected3 at risk EG003
Rhinitis	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0011 affected7 at risk EG0020 affected3 at risk EG003
Rhinitis allergic	Respiratory, thoracic and mediastinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected7 at risk EG0020 affected3 at risk EG003
Rhinorrhoea	Respiratory, thoracic and mediastinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0011 affected7 at risk EG0021 affected3 at risk EG003
Sciatica	Nervous system disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected7 at risk EG0021 affected3 at risk EG003
Sinus tachycardia	Cardiac disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected7 at risk EG0021 affected3 at risk EG003
Skin wound	Injury, poisoning and procedural complications	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected7 at risk EG0021 affected3 at risk EG003
Stomatitis	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0014 affected7 at risk EG0021 affected3 at risk EG003
Subdural haematoma	Injury, poisoning and procedural complications	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0011 affected7 at risk EG0020 affected3 at risk EG003
Supraventricular extrasystoles	Cardiac disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected7 at risk EG0020 affected3 at risk EG003
Swelling face	General disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected7 at risk EG0021 affected3 at risk EG003
Throat irritation	Respiratory, thoracic and mediastinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected7 at risk EG0021 affected3 at risk EG003
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0011 affected7 at risk EG0020 affected3 at risk EG003
Thyroid cyst	Endocrine disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected7 at risk EG0021 affected3 at risk EG003
Tinea cruris	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected7 at risk EG0020 affected3 at risk EG003
Tinea infection	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected7 at risk EG0021 affected3 at risk EG003
Toothache	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected7 at risk EG0020 affected3 at risk EG003
Tumour lysis syndrome	Metabolism and nutrition disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0012 affected7 at risk EG0020 affected3 at risk EG003
Upper respiratory tract infection	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0011 affected7 at risk EG0021 affected3 at risk EG003
Urinary retention	Renal and urinary disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected7 at risk EG0020 affected3 at risk EG003
Urticaria	Skin and subcutaneous tissue disorders	MedDRA 23.0	Systematic Assessment	EG0001 affected3 at risk EG0010 affected7 at risk EG0020 affected3 at risk EG003
Ventricular extrasystoles	Cardiac disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected7 at risk EG0020 affected3 at risk EG003
Ventricular tachycardia	Cardiac disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected7 at risk EG0020 affected3 at risk EG003
Vertigo	Ear and labyrinth disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected7 at risk EG0020 affected3 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0001 affected3 at risk EG0011 affected7 at risk EG0021 affected3 at risk EG003
Weight decreased	Investigations	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0012 affected7 at risk EG0020 affected3 at risk EG003
White blood cell count decreased	Investigations	MedDRA 23.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected7 at risk EG0021 affected3 at risk EG003

ID	Term
D015470	Leukemia, Myeloid, Acute
D009190	Myelodysplastic Syndromes

ID	Term
C539933	pevonedistat
D001374	Azacitidine

Ancestor Terms

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

Pevonedistat 10 mg/m^2, infusion, intravenously, on Days 1, 3, and 5 along with azacitidine 75 mg/m^2, injection, intravenously in Cycle 1 and intravenously or subcutaneously from Cycle 2 onwards, on Days 1 to 5, and Days 8 and 9, followed by a rest period of 19 days, in each 28-day treatment cycle until disease progression or symptomatic deterioration.

Pevonedistat 25 mg/m^2, infusion, intravenously, on Days 1, 3 and 5, followed by a rest period of 16 days, in each 21-day treatment cycle until disease progression or symptomatic deterioration.

Facility	Status	City	State	ZIP	Country	Contacts
		Maebashi			Japan

ID	Term
D007951	Leukemia, Myeloid
D007938	Leukemia
D009370	Neoplasms by Histologic Type
D009369	Neoplasms
D006402	Hematologic Diseases
D006425	Hemic and Lymphatic Diseases
D001855	Bone Marrow Diseases