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An Efficacy and Safety Study of Pevonedistat Plus Azacitidine Versus Single-Agent Azacitidine in Participants With Higher-Risk Myelodysplastic Syndromes (HR MDS), Chronic Myelomonocytic Leukemia (CMML) and Low-Blast Acute Myelogenous Leukemia (AML)

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ClinicalTrials.gov Identifier: NCT02610777
Recruitment Status : Active, not recruiting
First Posted : November 20, 2015
Results First Posted : September 23, 2020
Last Update Posted : January 6, 2021
Sponsor:
Information provided by (Responsible Party):
Takeda ( Millennium Pharmaceuticals, Inc. )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Myelodysplastic Syndromes
Leukemia, Myelomonocytic, Chronic
Leukemia, Myeloid, Acute
Interventions Drug: Azacitidine
Drug: Pevonedistat
Enrollment 120
Recruitment Details Participants took part in the study at 59 investigative sites in the United States, Canada, Belgium, Bulgaria, Czech Republic, Germany, Spain, France, Ireland, Israel, and Italy. Results are reported based on the primary completion date of 04 September 2019.
Pre-assignment Details Participants with higher-risk myelodysplastic syndrome (HR MDS) or chronic myelomonocytic leukemia (CMML) or low-blast acute myelogenous leukemia (AML) were enrolled in this study to receive one of the two treatments: single-agent azacitidine or the combination of pevonedistat and azacitidine.
Arm/Group Title Azacitidine 75 mg/m^2 Azacitidine 75 mg/m^2 + Pevonedistat 20 mg/m^2
Hide Arm/Group Description Azacitidine 75 milligram per square meter (mg/m^2), infusion, intravenously or subcutaneously, on Days 1 to 5, and on Days 8 and 9 in 28-day treatment cycles until unacceptable toxicity, relapse, transformation to AML (for participants with HR MDS or CMML), or progressive disease (for participants with low-blast AML). Azacitidine 75 mg/m^2, infusion, intravenously or subcutaneously, on Days 1 to 5, and on Days 8 and 9 and pevonedistat 20 mg/m^2, infusion, intravenously, on Days 1, 3, and 5 in 28-day treatment cycles until unacceptable toxicity, relapse, transformation to AML (for participants with HR MDS or CMML), or progressive disease (for participants with low-blast AML).
Period Title: Overall Study
Started 62 58
Completed 41 36
Not Completed 21 22
Reason Not Completed
Ongoing in Follow-up             14             12
Withdrawal by Subject             1             2
Other             0             1
Ongoing on Treatment             6             7
Arm/Group Title Azacitidine 75 mg/m^2 Azacitidine 75 mg/m^2 + Pevonedistat 20 mg/m^2 Total
Hide Arm/Group Description Azacitidine 75 mg/m^2, infusion, intravenously or subcutaneously, on Days 1 to 5, and on Days 8 and 9 in 28-day treatment cycles until unacceptable toxicity, relapse, transformation to AML (for participants with HR MDS or CMML), or progressive disease (for participants with low-blast AML). Azacitidine 75 mg/m^2, infusion, intravenously or subcutaneously, on Days 1 to 5, and on Days 8 and 9 and pevonedistat 20 mg/m^2, infusion, intravenously, on Days 1, 3, and 5 in 28-day treatment cycles until unacceptable toxicity, relapse, transformation to AML (for participants with HR MDS or CMML), or progressive disease (for participants with low-blast AML). Total of all reporting groups
Overall Number of Baseline Participants 62 58 120
Hide Baseline Analysis Population Description
The intent-to-treat (IIT) population was defined as all participants who were randomized.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 62 participants 58 participants 120 participants
69.5  (8.87) 71.7  (9.63) 70.6  (9.27)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 62 participants 58 participants 120 participants
Female
21
  33.9%
16
  27.6%
37
  30.8%
Male
41
  66.1%
42
  72.4%
83
  69.2%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 62 participants 58 participants 120 participants
Hispanic or Latino
3
   4.8%
4
   6.9%
7
   5.8%
Not Hispanic or Latino
55
  88.7%
52
  89.7%
107
  89.2%
Unknown or Not Reported
4
   6.5%
2
   3.4%
6
   5.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 62 participants 58 participants 120 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
3
   4.8%
1
   1.7%
4
   3.3%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
3
   4.8%
2
   3.4%
5
   4.2%
White
54
  87.1%
52
  89.7%
106
  88.3%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
2
   3.2%
3
   5.2%
5
   4.2%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 62 participants 58 participants 120 participants
Canada
3
   4.8%
3
   5.2%
6
   5.0%
United States
27
  43.5%
18
  31.0%
45
  37.5%
Belgium
5
   8.1%
5
   8.6%
10
   8.3%
Bulgaria
5
   8.1%
10
  17.2%
15
  12.5%
Czech Republic
3
   4.8%
1
   1.7%
4
   3.3%
Germany
0
   0.0%
1
   1.7%
1
   0.8%
Spain
8
  12.9%
14
  24.1%
22
  18.3%
France
1
   1.6%
1
   1.7%
2
   1.7%
Ireland
1
   1.6%
0
   0.0%
1
   0.8%
Israel
3
   4.8%
0
   0.0%
3
   2.5%
Italy
6
   9.7%
5
   8.6%
11
   9.2%
Height  
Mean (Standard Deviation)
Unit of measure:  Centimeter (cm)
Number Analyzed 62 participants 58 participants 120 participants
169.12  (10.857) 168.87  (7.510) 169.00  (9.352)
Weight  
Mean (Standard Deviation)
Unit of measure:  Kilogram (kg)
Number Analyzed 62 participants 58 participants 120 participants
79.19  (18.471) 75.95  (13.716) 77.62  (16.359)
Body Surface Area  
Mean (Standard Deviation)
Unit of measure:  Square meter (m^2)
Number Analyzed 62 participants 58 participants 120 participants
1.92  (0.265) 1.88  (0.201) 1.90  (0.236)
1.Primary Outcome
Title Overall Survival (OS)
Hide Description OS was defined as the time from the date of randomization to the date of death due to any cause. Participants without documented death at the time of the analysis were censored at the date the participant was last known to be alive.
Time Frame From date of randomization until death (up to 3 years and 5 months)
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT population was defined as all participants who were randomized.
Arm/Group Title Azacitidine 75 mg/m^2 Azacitidine 75 mg/m^2 + Pevonedistat 20 mg/m^2
Hide Arm/Group Description:
Azacitidine 75 mg/m^2, infusion, intravenously or subcutaneously, on Days 1 to 5, and on Days 8 and 9 in 28-day treatment cycles until unacceptable toxicity, relapse, transformation to AML (for participants with HR MDS or CMML), or progressive disease (for participants with low-blast AML).
Azacitidine 75 mg/m^2, infusion, intravenously or subcutaneously, on Days 1 to 5, and on Days 8 and 9 and pevonedistat 20 mg/m^2, infusion, intravenously, on Days 1, 3, and 5 in 28-day treatment cycles until unacceptable toxicity, relapse, transformation to AML (for participants with HR MDS or CMML), or progressive disease (for participants with low-blast AML).
Overall Number of Participants Analyzed 62 58
Median (95% Confidence Interval)
Unit of Measure: months
19.0
(13.57 to 27.73)
21.8
(18.53 to 28.78)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Azacitidine 75 mg/m^2, Azacitidine 75 mg/m^2 + Pevonedistat 20 mg/m^2
Comments Hazard Ratio (HR) was based on an unstratified Cox proportional hazard regression model with treatment as a factor. P-value is from an unstratified log-rank test.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.334
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.802
Confidence Interval (2-Sided) 95%
0.512 to 1.256
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Event-Free Survival (EFS)
Hide Description EFS is defined as the time from the date of randomization to the date of the occurrence of an event. An event is defined as death or transformation to AML for HR MDS/CMML participants, whichever occurs first, or defined as death for low-blast AML participants. HR MDS/CMML participants without documented EFS event will be censored at the date of the last response assessment. HR MDS/CMML participants with no response assessment and no death will be censored at the date of randomization. Low-blast AML participants without documentation of death will be censored at the date the participant was last known to be alive. HR MDS/CMML participants who received alternative antineoplastic therapy before death or transformation to AML will be censored at the date of last adequate assessment prior to starting alternate antineoplastic therapy. Data for this outcome measure will be reported after study completion (which is planned for 2022).
Time Frame From date of randomization until transformation to AML, or death due to any cause (up to 5 years and 9 months)
Outcome Measure Data Not Reported
3.Secondary Outcome
Title Six-month Survival Rate
Hide Description Six-month survival rate (at 6 months) was defined as the Kaplan-Meier estimate of survival rate at 6 months. OS was defined as the time from the date of randomization to the date of death due to any cause. Data for this outcome measure will be reported after study completion (which is planned for 2022).
Time Frame Month 6
Outcome Measure Data Not Reported
4.Secondary Outcome
Title One-year Survival Rate
Hide Description One-year survival rate (at 12 months) was defined as the Kaplan-Meier estimate of survival rate at 12 months. OS was defined as the time from the date of randomization to the date of death due to any cause. Data for this outcome measure will be reported after study completion (which is planned for 2022).
Time Frame Month 12
Outcome Measure Data Not Reported
5.Secondary Outcome
Title Time to AML Transformation in HR MDS or CMML Participants
Hide Description Time to AML transformation in HR MDS and CMML participants is defined as time from randomization to documented AML transformation. Participants who died before progression to AML will be censored. Transformation to AML is defined, according to World Health Organization (WHO) classification, as a participant having >20% blasts in the blood or marrow and increase of blast count by 50%. Data for this outcome measure will be reported after study completion (which is planned for 2022).
Time Frame From date of randomization until transformation to AML (up to 5 years and 9 months)
Outcome Measure Data Not Reported
6.Secondary Outcome
Title Percentage of Participants With Complete Remission (CR)
Hide Description Disease responses for HR MDS or CMML is based on the modified International Working Group (IWG) response criteria for MDS and for low-blast AML on the revised IWG response criteria for AML. CR for HR MDS or CMML: less than or equal to (<=) 5% myeloblasts with normal maturation of all cell lines in the bone marrow, and greater than or equal to (>=) 11 gram/deciliter (g/dL) hemoglobin (Hb), >=100*10^9/liter (/L) platelets (plt), >=1.0*10^9/L absolute neutrophil count (ANC) and 0% blasts in peripheral blood. CR for low-blast AML: morphologic leukemia-free state, ANC of more than 1.0*10^9/L and plt of >=1.0*10^9/L, transfusion independence, and no residual evidence of extramedullary leukemia. CR with incomplete blood count recovery for low-blast AML: some participants fulfill all of the criteria for CR except for residual neutropenia (<1.0*10^9/L) or thrombocytopenia (TTP) (<100*10^9/L). Data for this outcome measure will be reported after study completion (which is planned for 2022).
Time Frame From date of randomization until CR (up to 5 years and 9 months)
Outcome Measure Data Not Reported
7.Secondary Outcome
Title Percentage of Participants With CR and Partial Remission (PR)
Hide Description Disease responses for HR MDS/CMML per modified IWG response criteria for MDS and for low-blast AML on revised IWG response criteria for AML.CR for HR MDS/CMML: <=5% myeloblasts with normal maturation of all cell lines in bone marrow ,>=11 g/dL Hb;>=100*10^9/L plt; >=1.0*10^9/L ANC and 0% blasts in peripheral blood. PR for HR MDS/CMML:considered achieved if all CR criteria is met except for bone marrow blasts decreased by >=50%over pretreatment but still >5%. CR for low-blast AML: morphologic leukemia-free state, ANC of >1.0*10^9/L and plt of >=100*10^9/L, transfusion independence, no residual evidence of extramedullary leukemia. CR with incomplete blood count recovery for low-blast AML:fulfill all criteria for CR except for residual neutropenia (<100*10^9/L)/TTP(<100*10^9/L). PR for low-blast AML:all hematological values for CR but with decrease of >=50% in percentage of blasts to 5%-25% in bone marrow aspirate. Data will be reported after study completion (which is planned for 2022).
Time Frame From date of randomization until CR and PR (up to 5 years and 9 months)
Outcome Measure Data Not Reported
8.Secondary Outcome
Title Percentage of Participants With Overall Response
Hide Description Disease responses (HR MDS/CMML): modified IWG criteria for MDS; low-blast (LB) AML: revised IWG criteria for AML. Overall response(HR MDS/CMML)=CR,PR/HI,LB AML=CR+ CR with incomplete blood count recovery(Cri)+PR.HR MDS/CMML-CR:<=5%myeloblasts with normal maturation of bone marrow (BM) cell lines,>=11g/dL Hb,>=100*10^9/L plt,>=1.0*10^9/L ANC,0% blasts in peripheral blood; PR:CR criteria met except BM blasts>=50%less over pretreatment but still>5%; HI:hb increase (inc)>=1.5g/dL if baseline<11g/dL;plt inc>=30*10^9/L if baseline>20*10^9/L/Inc. from <20*10^9/L->20*10^9/L, ANC inc. by 100%;absolute inc. of>0.5*10^9/L if baseline<100*10^9/L. LB AML-CR:morphologic leukemia-freestate>1.0*10^9ANC,>=100*10^9/L plt, transfusion independence, no residual evidence of extramedullary leukemia;CRi:fulfill CR criteria except residual neutropenia<1.0*10^9/L/TTP<100*10^9/L;PR:all CR hematological values but>=50%less in BM aspirate. Data will be reported after study completion (which is planned for 2022).
Time Frame From date of randomization until CR, PR, or hematologic improvement (HI) (up to 5 years and 9 months)
Outcome Measure Data Not Reported
9.Secondary Outcome
Title Percentage of Participants With CR in Low-blast AML
Hide Description Disease response for low-blast AML is based on the revised IWG response criteria for AML. CR for low-blast AML: morphologic leukemia-free state, ANC of more than 1.0*10^9/L and plt of >=1.0*10^9/L, transfusion independence, and no residual evidence of extramedullary leukemia. CR with incomplete blood count recovery for low-blast AML: some participants fulfill all of the criteria for CR except for residual neutropenia (<1.0*10^9/L) or thrombocytopenia (TTP) (<100*10^9/L). Data for this outcome measure will be reported after study completion (which is planned for 2022).
Time Frame From date of randomization until CR (up to 5 years and 9 months)
Outcome Measure Data Not Reported
10.Secondary Outcome
Title Percentage of Participants With CR by Cycle 4
Hide Description Disease responses for HR MDS or CMML were based on modified IWG response criteria for MDS and for low-blast AML on revised IWG response criteria for AML. CR for HR MDS or CMML: <=5% myeloblasts with normal maturation of all cell lines in bone marrow, and >=11 g/dL Hb, >=100*10^9/L plt, ANC >=1.0*10^9/L and 0% blasts in peripheral blood. CR for low-blast AML: morphologic leukemia-free state, ANC of more than 1.0*10^9/L and plt of >=100*10^9/L, transfusion independence, no residual evidence of extramedullary leukemia. CR with incomplete blood count recovery for low-blast AML: some participants fulfill all criteria for CR except for residual neutropenia (<1.0*10^9/L)/TTP (<100*10^9/L).Data for this outcome measure will be reported after study completion (which is planned for 2022).
Time Frame From date of randomization until CR by Cycle 4 (cycle length is equal to [=] 28 days)
Outcome Measure Data Not Reported
11.Secondary Outcome
Title Percentage of Participants With CR and PR by Cycle 4
Hide Description Disease responses for HR MDS/CMML per modified IWG response criteria for MDS and for low-blast AML on revised IWG response criteria for AML.CR for HR MDS/CMML: <=5% myeloblasts with normal maturation of all cell lines in bone marrow, >=11 g/dL Hb; >=100*10^9/L plt; >=1.0*10^9/L ANC and 0% blasts in peripheral blood.PR for HR MDS/CMML: considered achieved if all CR criteria is met except for bone marrow blasts decreased by>=50% over pretreatment but still>5%.CR for low-blast AML: morphologic leukemia-free state, ANC of>1.0*10^9/L and plt of>=100*10^9/L, transfusion independence, no residual evidence of extramedullary leukemia. CR with incomplete blood count recovery for low-blast AML: fulfill all criteria for CR except for residual neutropenia (<100*10^9/L)/TTP (<100*10^9/L). PR for low-blast AML: all hematological values for CR but with decrease of >=50% in percentage of blasts to 5%-25% in bone marrow aspirate. Data will be reported after study completion (which is planned for 2022).
Time Frame From date of randomization until CR and PR, by Cycle 4 (cycle length=28 days)
Outcome Measure Data Not Reported
12.Secondary Outcome
Title Percentage of Participants With Overall Response by Cycle 4
Hide Description Disease responses (HR MDS/CMML): modified IWG criteria for MDS; low-blast (LB) AML: revised IWG criteria for AML. Overall response(HR MDS/CMML)=CR,PR/HI,LB AML=CR+ CR with incomplete blood count recovery(Cri)+PR.HR MDS/CMML-CR:<=5%myeloblasts with normal maturation of bone marrow (BM) cell lines,>=11g/dL Hb,>=100*10^9/L plt,>=1.0*10^9/L ANC,0% blasts in peripheral blood; PR:CR criteria met except BM blasts>=50%less over pretreatment but still>5%; HI:hb increase (inc)>=1.5g/dL if baseline<11g/dL;plt inc>=30*10^9/L if baseline>20*10^9/L/Inc. from <20*10^9/L->20*10^9/L, ANC inc. by 100%;absolute inc. of>0.5*10^9/L if baseline<100*10^9/L. LB AML-CR:morphologic leukemia-freestate>1.0*10^9ANC,>=100*10^9/L plt, transfusion independence, no residual evidence of extramedullary leukemia;CRi:fulfill CR criteria except residual neutropenia<1.0*10^9/L/TTP<100*10^9/L;PR:all CR hematological values but>=50%less in BM aspirate. Data will be reported after study completion (which is planned for 2022).
Time Frame From date of randomization until CR, PR or HI, by Cycle 4 (cycle length=28 days)
Outcome Measure Data Not Reported
13.Secondary Outcome
Title Percentage of Participants With CR in Low-blast AML by Cycle 4
Hide Description Disease response for low-blast AML is based on revised IWG response criteria for AML. CR for low-blast AML: morphologic leukemia-free state, ANC of more than 1.0*10^9/L and ptl of >=100*10^9/L, transfusion independence, no residual evidence of extramedullary leukemia. CR with incomplete blood count recovery for low-blast AML: some participants fulfill all criteria for CR except for residual neutropenia (<1.0*10^9/L)/TTP (<100*10^9/L). Data for this outcome measure will be reported after study completion (which is planned for 2022).
Time Frame From the date of randomization until CR by Cycle 4 (cycle length=28 days)
Outcome Measure Data Not Reported
14.Secondary Outcome
Title Duration of CR
Hide Description Duration of CR will be analyzed using standard survival analysis techniques based on Kaplan Meier estimates. Disease responses for HR MDS or CMML are based on modified IWG response criteria for MDS and for low-blast AML on revised IWG response criteria for AML. CR for HR MDS or CMML: <=5% myeloblasts with normal maturation of all cell lines in bone marrow, and >=11 g/dL Hb, >=100*10^9/L plt, >=1.0*10^9/L ANC and 0% blasts in peripheral blood. CR for low-blast AML: morphologic leukemia-free state, ANC of more than 1.0*10^9/L and plt of >=100*10^9/L, transfusion independence, no residual evidence of extramedullary leukemia. CR with incomplete blood count recovery for low-blast AML: some participants fulfill all criteria for CR except for residual neutropenia (<1.0*10^9/L)/TTP (<100*10^9/L). Data for this outcome measure will be reported after study completion (which is planned for 2022).
Time Frame From date of randomization until CR (up to 5 years and 9 months)
Outcome Measure Data Not Reported
15.Secondary Outcome
Title Duration of CR and PR
Hide Description Duration of CR and PR will be analyzed by standard survival analysis techniques based on Kaplan Meier estimates. Disease responses (HR MDS/CMML) are based on modified IWG response criteria for MDS and for low-blast AML on revised IWG response criteria for AML. For HR MDS/CMML-CR:<=5%myeloblasts with normal maturation of all bone marrow cell lines, >=11 g/dL Hb, >=100*10^9/L plt,>=1.0*10^9/L neutrophils, 0% blasts in peripheral blood;PR: all CR criteria met except bone marrow blasts >=50% decrease over pretreatment but still >5%; low-blast AML-CR: morphologic leukemia-free state, >1.0*10^9/L ANC ,plt >=100*10^9/L,transfusion independence, no residual evidence of extramedullary leukemia;CR with incomplete blood count recovery:fulfill CR criteria except residual neutropenia <1.0*10^9/L/TTP <100*10^9/L;PR:all CR hematological values but with a decrease of >=50% in blasts percentage to 5%-25% in bone marrow aspirate. Data will be reported after study completion (which is planned for 2022).
Time Frame From date of randomization until CR or PR (up to 5 years and 9 months)
Outcome Measure Data Not Reported
16.Secondary Outcome
Title Duration of Overall Response
Hide Description Disease responses(HR MDS/CMML): modified IWG criteria for MDS;low-blast(LB)AML: revised IWG criteria for AML.Overall response(HR MDS/CMML)=CR,PR/HI,LB AML=CR+CR with incomplete blood count recovery(Cri)+PR.HR MDS/CMML-CR: <=5%myeloblasts with normal maturation of bone marrow (BM) cell lines, >=11g/dL Hb,>=100*10^9/L plt, >=1.0*10^9/L ANC,0%blasts in peripheral blood; PR:CR criteria met except BM blasts >=50%less over pretreatment but still>5%; HI:hb increase(inc) >=1.5g/dL if baseline<11g/dL; plt inc>=30*10^9/L if baseline >20*10^9/L inc from<20*10^9/L->20*10^9/L,ANC inc by100%; absolute inc of >0.5*10^9/L if baseline <100*10^9/L.LB AML-CR: morphologic leukemia-freestate >1.0*10^9 ANC, >=100*1 ^9/Lplt, transfusion independence, no residual evidence of extramedullary leukemia; CRi:fulfill CR criteria except residual neutropenia<1.0*10^9/L/TTP<100*10^9/L; PR:all CR hematological values but>=50%less in BM aspirate. Data will be reported after study completion (which is planned for 2022).
Time Frame From date of randomization until CR, PR or HI (up to 5 years and 9 months)
Outcome Measure Data Not Reported
17.Secondary Outcome
Title Duration of CR in Low-blast AML
Hide Description Duration of CR was analyzed using standard survival analysis techniques based on Kaplan Meier estimates. Disease responses for low-blast AML is based on revised IWG response criteria for AML. CR for low-blast AML: morphologic leukemia-free state, ANC of more than 1.0*10^9/L and plt of >=100*10^9/L, transfusion independence, no residual evidence of extramedullary leukemia. CR with incomplete blood count recovery for low-blast AML: some participants fulfill all criteria for CR except for residual neutropenia (<1.0*10^9/L)/TTP (<100*10^9/L). Data for this outcome measure will be reported after study completion (which is planned for 2022).
Time Frame From date of randomization until CR (up to 5 years and 9 months)
Outcome Measure Data Not Reported
18.Secondary Outcome
Title Time to First CR or PR
Hide Description Time to first CR or PR: time from randomization to first documented CR or PR, whichever occurs first. Disease responses (HR MDS/CMML) based on modified IWG response criteria for MDS; low-blast AML on revised IWG response criteria for AML. HR MDS/CMML-CR: <=5% myeloblasts with normal maturation of all bone marrow cell lines, >=11 g/dL Hb, >=100*10^9/L plt,>=1.0*10^9/L ANC, 0% blasts in peripheral blood; PR: all CR criteria met except bone marrow blasts >=50% decrease over pretreatment but still >5%; For low-blast AML-CR: morphologic leukemia-free state, >1.0*10^9/L ANC, plt >=100*10^9/L, transfusion independence, no residual evidence of extramedullary leukemia; CR with incomplete blood count recovery: fulfill CR criteria except residual neutropenia <1.0*10^9/L/TTP <100*10^9/L; PR: all CR hematological values but with a decrease of >=50% in the percentage of blasts to 5% to 25% in the bone marrow aspirate. Data will be reported after study completion (which is planned for 2022).
Time Frame From date of randomization until CR or PR (up to 5 years and 9 months)
Outcome Measure Data Not Reported
19.Secondary Outcome
Title Time to Subsequent Therapy
Hide Description Time to subsequent therapy is defined as time from randomization to the date of the first subsequent therapy. Subsequent therapy is defined as agent(s) with antileukemic/anti-MDS activity. Participants who discontinue study treatment to receive single-agent azacitidine off study will not be counted as receiving subsequent therapy. Data for this outcome measure will be reported after study completion (which is planned for 2022).
Time Frame From date of randomization up to 5 year 9 months
Outcome Measure Data Not Reported
20.Secondary Outcome
Title Percentage of Participants With Red Blood Cells (RBCs) and Platelet-transfusion Independence
Hide Description A participant was defined as RBC or platelet-transfusion independent if he/she receives no RBC or platelet transfusions for a period of at least 8 weeks before randomization through 30 days after the last dose of any study drug. Rate of transfusion independence is defined as number of participants who become transfusion independent divided by the number of participants who are transfusion dependent at Baseline. Data for this outcome measure will be reported after study completion (which is planned for 2022).
Time Frame 8 weeks before randomization through 30 days after last dose of any study drug (up to 5 years and 9 months)
Outcome Measure Data Not Reported
21.Secondary Outcome
Title Percentage of Participants With at Least 1 Inpatient Hospital Admissions Related to HR MDS, CMML or Low-blast AML
Hide Description Inpatient hospital admission data will be collected through transformation to AML (HR MDS/CMML participants) or disease progression (low-blast AML participants) or until initiation of subsequent therapy (all participants), whichever occurs first. Transformation to AML is defined, according to WHO Classification, as a participant having >20% blasts in the blood or marrow and increase of blast count by 50%. Data for this outcome measure will be reported after study completion (which is planned for 2022).
Time Frame From date of randomization until transformation to AML or until initiation of subsequent therapy (up to 5 years and 9 months)
Outcome Measure Data Not Reported
22.Secondary Outcome
Title Time to Progressive Disease (PD), Relapse, or Death
Hide Description Time from randomization until PD/transformation to AML/relapse/death due to any cause, whichever occurs first. Relapse after CR or PR in MDS/CMML: return to pretreatment bone marrow blast % or decrement of >=50% from maximum remission levels in ANC or plt, reduction in Hb concentration by >=1.5 g/dL or transfusion dependence. PD: at least 50% decrement from maximum remission in ANC or plt, or reduction in Hb by>=2g/dL or transfusion dependence;participants with <5% blasts: >=50% increase (inc) in blasts to >5%; 5%-10%: >=50% inc to >10%; 10%-20%: >=50% inc to>20%;20%-30%:>=50% inc to >30%. Relapse after CR in Low blast AML: reappearance of leukemic blasts in peripheral blood or >=5% blasts in bone marrow not attributable to any cause (example, bone marrow regeneration after consolidation therapy). If there are no circulating blasts, bone marrow contains 5%-20% blasts, a repeat analysis is performed a week later. Data will be reported after study completion (which is planned for 2022).
Time Frame From date of randomization until PD, relapse or death (up to 5 years and 9 months)
Outcome Measure Data Not Reported
23.Secondary Outcome
Title Number of Participants Reporting One or More Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Hide Description Data for this outcome measure will be reported after study completion (which is planned for 2022).
Time Frame From date of randomization up to 30 days after administration of the last dose of any study drug (up to 5 years and 9 months)
Outcome Measure Data Not Reported
24.Secondary Outcome
Title Number of Participants With Markedly Abnormal Clinical Laboratory Values
Hide Description Data for this outcome measure will be reported after study completion (which is planned for 2022).
Time Frame From date of randomization up to 30 days after administration of the last dose of any study drug (up to 5 years and 9 months)
Outcome Measure Data Not Reported
25.Secondary Outcome
Title Number of Participants With Change From Baseline Values in Eastern Cooperative Oncology Group (ECOG) Performance Status
Hide Description Number of participants with change from Baseline in ECOG performance status was measured on 6 point scale to assess participant's performance status, where: Grade 0(Normal activity. Fully active, able to carry on all pre-disease activities without restriction); Grade 1(Symptoms but ambulatory. Restricted in physically strenuous activity, but ambulatory and able to carry out light or sedentary work); Grade 2(In bed <50% of the time. Ambulatory and capable of all self-care, but unable to carry out any work activities. Up and about more than 50% of waking hours); Grade 3(In bed >50% of the time. Capable of only limited self-care, confined to bed or chair more than 50 percent of waking hours); Grade 4(100% bedridden. Completely disabled, cannot carry on any self-care, totally confined to bed or chair); Grade 5(Dead). Data for this outcome measure will be reported after study completion (which is planned for 2022).
Time Frame From date of randomization up to 30 days after administration of the last dose of any study drug (up to 5 years and 9 months)
Outcome Measure Data Not Reported
26.Secondary Outcome
Title Number of Participants With Significant Change From Baseline in Electrocardiogram (ECG) Values
Hide Description Data for this outcome measure will be reported after study completion (which is planned for 2022).
Time Frame From date of randomization up to 30 days after administration of the last dose of any study drug (up to 5 years and 9 months)
Outcome Measure Data Not Reported
27.Secondary Outcome
Title Number of Participants With Clinically Significant Change From Baseline Values in Vital Signs
Hide Description Data for this outcome measure will be reported after study completion (which is planned for 2022).
Time Frame From date of randomization up to 30 days after administration of the last dose of any study drug (up to 5 years and 9 months)
Outcome Measure Data Not Reported
Time Frame TEAEs are adverse events (AEs) that started after the date of randomization up to 30 days after administration of the last dose of any study drug (up to 3 years and 5 months)
Adverse Event Reporting Description At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
 
Arm/Group Title Azacitidine 75 mg/m^2 Azacitidine 75 mg/m^2 + Pevonedistat 20 mg/m^2
Hide Arm/Group Description Azacitidine 75 mg/m^2, infusion, intravenously or subcutaneously, on Days 1 to 5, and on Days 8 and 9 in 28-day treatment cycles until unacceptable toxicity, relapse, transformation to AML (for participants with HR MDS or CMML), or progressive disease (for participants with low-blast AML). Azacitidine 75 mg/m^2, infusion, intravenously or subcutaneously, on Days 1 to 5, and on Days 8 and 9 and pevonedistat 20 mg/m^2, infusion, intravenously, on Days 1, 3, and 5 in 28-day treatment cycles until unacceptable toxicity, relapse, transformation to AML (for participants with HR MDS or CMML), or progressive disease (for participants with low-blast AML).
All-Cause Mortality
Azacitidine 75 mg/m^2 Azacitidine 75 mg/m^2 + Pevonedistat 20 mg/m^2
Affected / at Risk (%) Affected / at Risk (%)
Total   41/62 (66.13%)      36/58 (62.07%)    
Hide Serious Adverse Events
Azacitidine 75 mg/m^2 Azacitidine 75 mg/m^2 + Pevonedistat 20 mg/m^2
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   39/62 (62.90%)      40/58 (68.97%)    
Blood and lymphatic system disorders     
Febrile neutropenia  1  13/62 (20.97%)  15 13/58 (22.41%)  20
Anaemia  1  2/62 (3.23%)  2 0/58 (0.00%)  0
Thrombocytopenia  1  1/62 (1.61%)  1 1/58 (1.72%)  1
Autoimmune haemolytic anaemia  1  1/62 (1.61%)  1 0/58 (0.00%)  0
Leukopenia  1  1/62 (1.61%)  1 0/58 (0.00%)  0
Neutropenia  1  1/62 (1.61%)  1 0/58 (0.00%)  0
Cardiac disorders     
Atrial fibrillation  1  1/62 (1.61%)  1 1/58 (1.72%)  1
Angina unstable  1  0/62 (0.00%)  0 1/58 (1.72%)  1
Atrial flutter  1  0/62 (0.00%)  0 1/58 (1.72%)  1
Atrioventricular block  1  0/62 (0.00%)  0 1/58 (1.72%)  1
Atrioventricular block second degree  1  0/62 (0.00%)  0 1/58 (1.72%)  1
Cardiac failure  1  0/62 (0.00%)  0 1/58 (1.72%)  1
Cardiac failure acute  1  0/62 (0.00%)  0 1/58 (1.72%)  1
Cardio-respiratory arrest  1  0/62 (0.00%)  0 1/58 (1.72%)  1
Congestive cardiomyopathy  1  1/62 (1.61%)  1 0/58 (0.00%)  0
Left ventricular failure  1  0/62 (0.00%)  0 1/58 (1.72%)  1
Myocardial infarction  1  1/62 (1.61%)  1 0/58 (0.00%)  0
Supraventricular tachycardia  1  1/62 (1.61%)  1 0/58 (0.00%)  0
Ear and labyrinth disorders     
Ear pain  1  0/62 (0.00%)  0 1/58 (1.72%)  1
Eye disorders     
Parophthalmia  1  0/62 (0.00%)  0 1/58 (1.72%)  1
Gastrointestinal disorders     
Abdominal pain  1  0/62 (0.00%)  0 2/58 (3.45%)  2
Diarrhoea  1  0/62 (0.00%)  0 2/58 (3.45%)  2
Constipation  1  1/62 (1.61%)  1 0/58 (0.00%)  0
Gastric haemorrhage  1  1/62 (1.61%)  1 0/58 (0.00%)  0
Gastritis erosive  1  1/62 (1.61%)  1 0/58 (0.00%)  0
Gastrointestinal necrosis  1  1/62 (1.61%)  1 0/58 (0.00%)  0
Gastrointestinal ulcer perforation  1  1/62 (1.61%)  1 0/58 (0.00%)  0
Inguinal hernia  1  1/62 (1.61%)  1 0/58 (0.00%)  0
Ischaemic gastritis  1  1/62 (1.61%)  1 0/58 (0.00%)  0
Melaena  1  0/62 (0.00%)  0 1/58 (1.72%)  1
Proctitis  1  0/62 (0.00%)  0 1/58 (1.72%)  1
Rectal haemorrhage  1  1/62 (1.61%)  1 0/58 (0.00%)  0
General disorders     
Pyrexia  1  6/62 (9.68%)  8 3/58 (5.17%)  3
Multiple organ dysfunction syndrome  1  1/62 (1.61%)  1 1/58 (1.72%)  1
Asthenia  1  0/62 (0.00%)  0 1/58 (1.72%)  1
Malaise  1  1/62 (1.61%)  2 0/58 (0.00%)  0
Non-cardiac chest pain  1  0/62 (0.00%)  0 1/58 (1.72%)  1
Death  1  1/62 (1.61%)  1 0/58 (0.00%)  0
Hepatobiliary disorders     
Hepatic lesion  1  1/62 (1.61%)  1 0/58 (0.00%)  0
Immune system disorders     
Drug hypersensitivity  1  1/62 (1.61%)  1 0/58 (0.00%)  0
Infections and infestations     
Pneumonia  1  5/62 (8.06%)  7 7/58 (12.07%)  11
Sepsis  1  4/62 (6.45%)  4 3/58 (5.17%)  3
Cellulitis  1  2/62 (3.23%)  2 2/58 (3.45%)  2
Bacteraemia  1  1/62 (1.61%)  1 2/58 (3.45%)  2
Endocarditis  1  1/62 (1.61%)  1 2/58 (3.45%)  2
Bronchopulmonary aspergillosis  1  1/62 (1.61%)  1 1/58 (1.72%)  1
Influenza  1  1/62 (1.61%)  1 1/58 (1.72%)  1
Lung infection  1  1/62 (1.61%)  3 1/58 (1.72%)  1
Upper respiratory tract infection  1  0/62 (0.00%)  0 2/58 (3.45%)  2
Wound infection  1  1/62 (1.61%)  1 1/58 (1.72%)  1
Abscess limb  1  0/62 (0.00%)  0 1/58 (1.72%)  1
Arthritis bacterial  1  0/62 (0.00%)  0 1/58 (1.72%)  1
Arthritis infective  1  0/62 (0.00%)  0 1/58 (1.72%)  1
Bacterial sepsis  1  1/62 (1.61%)  1 0/58 (0.00%)  0
Bronchitis  1  0/62 (0.00%)  0 1/58 (1.72%)  1
Corona virus infection  1  0/62 (0.00%)  0 1/58 (1.72%)  1
Localised infection  1  0/62 (0.00%)  0 1/58 (1.72%)  1
Lower respiratory tract infection  1  1/62 (1.61%)  1 0/58 (0.00%)  0
Oral viral infection  1  0/62 (0.00%)  0 1/58 (1.72%)  1
Pseudomonas infection  1  0/62 (0.00%)  0 1/58 (1.72%)  1
Pulmonary sepsis  1  0/62 (0.00%)  0 1/58 (1.72%)  1
Respiratory syncytial virus bronchiolitis  1  0/62 (0.00%)  0 1/58 (1.72%)  1
Respiratory tract infection  1  1/62 (1.61%)  1 0/58 (0.00%)  0
Sinusitis  1  0/62 (0.00%)  0 1/58 (1.72%)  1
Soft tissue infection  1  1/62 (1.61%)  1 0/58 (0.00%)  0
Staphylococcal bacteraemia  1  0/62 (0.00%)  0 1/58 (1.72%)  1
Urinary tract infection  1  1/62 (1.61%)  1 0/58 (0.00%)  0
Urinary tract infection enterococcal  1  1/62 (1.61%)  1 0/58 (0.00%)  0
Viral infection  1  0/62 (0.00%)  0 1/58 (1.72%)  1
Injury, poisoning and procedural complications     
Ankle fracture  1  1/62 (1.61%)  1 0/58 (0.00%)  0
Fall  1  1/62 (1.61%)  1 0/58 (0.00%)  0
Hip fracture  1  0/62 (0.00%)  0 1/58 (1.72%)  1
Postoperative hypotension  1  1/62 (1.61%)  1 0/58 (0.00%)  0
Spinal compression fracture  1  1/62 (1.61%)  1 0/58 (0.00%)  0
Metabolism and nutrition disorders     
Failure to thrive  1  1/62 (1.61%)  1 0/58 (0.00%)  0
Hyperglycaemia  1  0/62 (0.00%)  0 1/58 (1.72%)  1
Musculoskeletal and connective tissue disorders     
Back pain  1  0/62 (0.00%)  0 2/58 (3.45%)  2
Arthritis  1  1/62 (1.61%)  2 0/58 (0.00%)  0
Arthritis reactive  1  1/62 (1.61%)  1 0/58 (0.00%)  0
Chondrocalcinosis pyrophosphate  1  0/62 (0.00%)  0 1/58 (1.72%)  1
Osteonecrosis  1  0/62 (0.00%)  0 1/58 (1.72%)  1
Rotator cuff syndrome  1  0/62 (0.00%)  0 1/58 (1.72%)  1
Pain in jaw  1  0/62 (0.00%)  0 1/58 (1.72%)  1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Acute myeloid leukaemia  1  1/62 (1.61%)  1 0/58 (0.00%)  0
Myelodysplastic syndrome  1  1/62 (1.61%)  1 0/58 (0.00%)  0
Myelodysplastic syndrome transformation  1  1/62 (1.61%)  1 0/58 (0.00%)  0
Squamous cell carcinoma of skin  1  0/62 (0.00%)  0 1/58 (1.72%)  2
Nervous system disorders     
Cerebrovascular accident  1  2/62 (3.23%)  3 0/58 (0.00%)  0
Cauda equina syndrome  1  1/62 (1.61%)  1 0/58 (0.00%)  0
Cerebral ischaemia  1  0/62 (0.00%)  0 1/58 (1.72%)  1
Embolic stroke  1  1/62 (1.61%)  1 0/58 (0.00%)  0
Haemorrhage intracranial  1  1/62 (1.61%)  1 0/58 (0.00%)  0
Headache  1  1/62 (1.61%)  1 0/58 (0.00%)  0
Psychiatric disorders     
Mental status changes  1  0/62 (0.00%)  0 2/58 (3.45%)  2
Renal and urinary disorders     
Acute kidney injury  1  0/62 (0.00%)  0 2/58 (3.45%)  2
Urinary tract obstruction  1  1/62 (1.61%)  1 1/58 (1.72%)  1
Anuria  1  0/62 (0.00%)  0 1/58 (1.72%)  1
Chronic kidney disease  1  1/62 (1.61%)  1 0/58 (0.00%)  0
Haematuria  1  0/62 (0.00%)  0 1/58 (1.72%)  1
Renal colic  1  1/62 (1.61%)  1 0/58 (0.00%)  0
Renal failure  1  0/62 (0.00%)  0 1/58 (1.72%)  1
Reproductive system and breast disorders     
Benign prostatic hyperplasia  1  0/62 (0.00%)  0 1/58 (1.72%)  1
Respiratory, thoracic and mediastinal disorders     
Dyspnoea  1  1/62 (1.61%)  1 1/58 (1.72%)  1
Hypoxia  1  1/62 (1.61%)  2 0/58 (0.00%)  0
Lung infiltration  1  1/62 (1.61%)  1 0/58 (0.00%)  0
Pulmonary embolism  1  0/62 (0.00%)  0 1/58 (1.72%)  2
Respiratory distress  1  0/62 (0.00%)  0 1/58 (1.72%)  1
Respiratory failure  1  0/62 (0.00%)  0 1/58 (1.72%)  1
Skin and subcutaneous tissue disorders     
Acute febrile neutrophilic dermatosis  1  1/62 (1.61%)  1 0/58 (0.00%)  0
Vascular disorders     
Deep vein thrombosis  1  0/62 (0.00%)  0 1/58 (1.72%)  1
Haematoma  1  0/62 (0.00%)  0 1/58 (1.72%)  1
Peripheral venous disease  1  0/62 (0.00%)  0 1/58 (1.72%)  1
Thrombophlebitis superficial  1  1/62 (1.61%)  1 0/58 (0.00%)  0
1
Term from vocabulary, MedDRA 22.0
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Azacitidine 75 mg/m^2 Azacitidine 75 mg/m^2 + Pevonedistat 20 mg/m^2
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   60/62 (96.77%)      52/58 (89.66%)    
Blood and lymphatic system disorders     
Anaemia  1  26/62 (41.94%)  48 18/58 (31.03%)  35
Neutropenia  1  18/62 (29.03%)  39 20/58 (34.48%)  62
Thrombocytopenia  1  14/62 (22.58%)  34 13/58 (22.41%)  35
Febrile neutropenia  1  5/62 (8.06%)  7 2/58 (3.45%)  2
Cardiac disorders     
Tachycardia  1  2/62 (3.23%)  2 4/58 (6.90%)  4
Ear and labyrinth disorders     
Ear pain  1  0/62 (0.00%)  0 3/58 (5.17%)  3
Eye disorders     
Conjunctival haemorrhage  1  2/62 (3.23%)  3 3/58 (5.17%)  3
Gastrointestinal disorders     
Constipation  1  29/62 (46.77%)  38 21/58 (36.21%)  38
Nausea  1  28/62 (45.16%)  39 20/58 (34.48%)  34
Diarrhoea  1  17/62 (27.42%)  28 18/58 (31.03%)  25
Vomiting  1  13/62 (20.97%)  17 14/58 (24.14%)  22
Abdominal pain  1  10/62 (16.13%)  11 3/58 (5.17%)  5
Haemorrhoids  1  2/62 (3.23%)  2 5/58 (8.62%)  6
Stomatitis  1  5/62 (8.06%)  5 1/58 (1.72%)  1
General disorders     
Pyrexia  1  22/62 (35.48%)  31 21/58 (36.21%)  36
Fatigue  1  25/62 (40.32%)  33 12/58 (20.69%)  20
Asthenia  1  12/62 (19.35%)  19 17/58 (29.31%)  27
Oedema peripheral  1  8/62 (12.90%)  11 12/58 (20.69%)  17
Chills  1  7/62 (11.29%)  7 4/58 (6.90%)  4
Injection site pain  1  7/62 (11.29%)  7 4/58 (6.90%)  5
Peripheral swelling  1  2/62 (3.23%)  2 5/58 (8.62%)  6
Non-cardiac chest pain Pain  1  4/62 (6.45%)  6 2/58 (3.45%)  2
Malaise  1  4/62 (6.45%)  4 0/58 (0.00%)  0
Injection site reaction  1  0/62 (0.00%)  0 3/58 (5.17%)  3
Pain  1  3/62 (4.84%)  3 3/58 (5.17%)  3
Infections and infestations     
Nasopharyngitis  1  4/62 (6.45%)  4 7/58 (12.07%)  10
Pneumonia  1  6/62 (9.68%)  6 3/58 (5.17%)  3
Urinary tract infection  1  4/62 (6.45%)  10 5/58 (8.62%)  8
Oral candidiasis  1  4/62 (6.45%)  4 3/58 (5.17%)  3
Oral herpes  1  6/62 (9.68%)  7 1/58 (1.72%)  1
Bronchitis  1  6/62 (9.68%)  6 0/58 (0.00%)  0
Respiratory tract infection  1  3/62 (4.84%)  3 3/58 (5.17%)  3
Injury, poisoning and procedural complications     
Fall  1  6/62 (9.68%)  6 7/58 (12.07%)  9
Contusion  1  4/62 (6.45%)  4 5/58 (8.62%)  5
Investigations     
Neutrophil count decreased  1  6/62 (9.68%)  18 12/58 (20.69%)  22
Platelet count decreased  1  7/62 (11.29%)  19 7/58 (12.07%)  10
Weight decreased  1  5/62 (8.06%)  5 5/58 (8.62%)  7
White blood cell count decreased  1  6/62 (9.68%)  11 4/58 (6.90%)  12
Aspartate aminotransferase increased  1  5/62 (8.06%)  8 4/58 (6.90%)  6
Alanine aminotransferase increased  1  4/62 (6.45%)  8 4/58 (6.90%)  7
Blood bilirubin increased  1  3/62 (4.84%)  5 3/58 (5.17%)  8
Blood creatinine increased  1  3/62 (4.84%)  5 3/58 (5.17%)  3
Blood alkaline phosphatase increased  1  2/62 (3.23%)  9 3/58 (5.17%)  4
Metabolism and nutrition disorders     
Decreased appetite  1  12/62 (19.35%)  16 11/58 (18.97%)  11
Hypokalaemia  1  11/62 (17.74%)  17 4/58 (6.90%)  5
Hyponatraemia  1  4/62 (6.45%)  8 4/58 (6.90%)  16
Hypocalcaemia  1  4/62 (6.45%)  5 3/58 (5.17%)  5
Hypomagnesaemia  1  4/62 (6.45%)  6 3/58 (5.17%)  3
Dehydration  1  4/62 (6.45%)  5 2/58 (3.45%)  3
Hyperkalaemia  1  3/62 (4.84%)  9 3/58 (5.17%)  3
Hypoalbuminaemia  1  4/62 (6.45%)  10 2/58 (3.45%)  4
Hypophosphataemia  1  4/62 (6.45%)  4 1/58 (1.72%)  1
Musculoskeletal and connective tissue disorders     
Arthralgia  1  12/62 (19.35%)  15 5/58 (8.62%)  6
Back pain  1  8/62 (12.90%)  9 9/58 (15.52%)  11
Pain in extremity  1  4/62 (6.45%)  5 10/58 (17.24%)  12
Muscular weakness  1  5/62 (8.06%)  6 2/58 (3.45%)  3
Muscle spasms  1  3/62 (4.84%)  5 3/58 (5.17%)  3
Musculoskeletal pain  1  4/62 (6.45%)  4 1/58 (1.72%)  1
Myalgia  1  2/62 (3.23%)  2 3/58 (5.17%)  3
Nervous system disorders     
Dizziness  1  8/62 (12.90%)  10 8/58 (13.79%)  11
Headache  1  8/62 (12.90%)  10 3/58 (5.17%)  4
Somnolence  1  1/62 (1.61%)  1 3/58 (5.17%)  3
Psychiatric disorders     
Insomnia  1  7/62 (11.29%)  8 6/58 (10.34%)  6
Depression  1  2/62 (3.23%)  2 4/58 (6.90%)  5
Renal and urinary disorders     
Dysuria  1  2/62 (3.23%)  3 4/58 (6.90%)  4
Haematuria  1  1/62 (1.61%)  2 3/58 (5.17%)  4
Acute kidney injury  1  0/62 (0.00%)  0 3/58 (5.17%)  3
Respiratory, thoracic and mediastinal disorders     
Cough  1  21/62 (33.87%)  25 22/58 (37.93%)  31
Dyspnoea  1  15/62 (24.19%)  19 13/58 (22.41%)  15
Epistaxis  1  6/62 (9.68%)  6 13/58 (22.41%)  27
Productive cough  1  4/62 (6.45%)  5 6/58 (10.34%)  7
Nasal congestion  1  4/62 (6.45%)  5 5/58 (8.62%)  5
Oropharyngeal pain  1  6/62 (9.68%)  6 3/58 (5.17%)  3
Pleural effusion  1  5/62 (8.06%)  5 2/58 (3.45%)  2
Dyspnoea exertional  1  2/62 (3.23%)  2 3/58 (5.17%)  3
Skin and subcutaneous tissue disorders     
Erythema  1  5/62 (8.06%)  6 4/58 (6.90%)  5
Pruritus  1  6/62 (9.68%)  6 1/58 (1.72%)  1
Petechiae  1  4/62 (6.45%)  4 1/58 (1.72%)  1
Vascular disorders     
Haematoma  1  2/62 (3.23%)  2 7/58 (12.07%)  11
Hypotension  1  3/62 (4.84%)  4 6/58 (10.34%)  7
Hypertension  1  2/62 (3.23%)  2 4/58 (6.90%)  4
Pallor  1  1/62 (1.61%)  1 3/58 (5.17%)  3
1
Term from vocabulary, MedDRA 22.0
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The first study related publication will be a multi-center publication submitted within 24 months after conclusion or termination of a study at all sites. After such multi site publication, all proposed site publications and presentations will be submitted to sponsor for review 60 days in advance of publication. Site will remove Sponsor confidential information unrelated to study results. Sponsor can delay a proposed publication for another 60 days to preserve intellectual property.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Medical Director
Organization: Takeda
Phone: +1-877-825-3327
EMail: trialdisclosures@takeda.com
Layout table for additonal information
Responsible Party: Takeda ( Millennium Pharmaceuticals, Inc. )
ClinicalTrials.gov Identifier: NCT02610777    
Other Study ID Numbers: Pevonedistat-2001
U1111-1169-6540 ( Registry Identifier: WHO )
2015-000221-37 ( EudraCT Number )
REec-2016-2145 ( Registry Identifier: REec )
Pevonedistat-2001CTID ( Other Identifier: Israel )
First Submitted: November 18, 2015
First Posted: November 20, 2015
Results First Submitted: August 31, 2020
Results First Posted: September 23, 2020
Last Update Posted: January 6, 2021