Trial · NCT03268954
Pevonedistat Plus Azacitidine Versus Single-Agent Azacitidine as First-Line Treatment for Participants With Higher-Risk Myelodysplastic Syndromes (HR MDS), Chronic Myelomonocytic Leukemia (CMML), or Low-Blast Acute Myelogenous Leukemia (AML)
NCT03268954, Phase 3, Completed, Takeda; results first posted 2022-09-22
3 sourcestrials-2026-11-12-0.5.0
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ConductScience Library. Pevonedistat Plus Azacitidine Versus Single-Agent Azacitidine as First-Line Treatment for Participants With Higher-Risk Myelodysplastic Syndromes (HR MDS), Chronic Myelomonocytic Leukemia (CMML), or Low-Blast Acute Myelogenous Leukemia (AML). Trials, record NCT03268954. Release trials-2026-11-12-0.5.0, 12 Nov 2026. https://conductscience.org/library/trials/NCT03268954
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Trial
As registered on ClinicalTrials.gov, in the graph's capture of the registry.
- Title
Pevonedistat Plus Azacitidine Versus Single-Agent Azacitidine as First-Line Treatment for Participants With Higher-Risk Myelodysplastic Syndromes (HR MDS), Chronic Myelomonocytic Leukemia (CMML), or Low-Blast Acute Myelogenous Leukemia (AML)
- NCT number
- NCT03268954
- Status
- Completed
- Phases
- Phase 3
- Enrollment
- 454 participants, actual
- Lead sponsor
- Takeda
- Conditions
- Myelodysplastic Syndrome, Leukemia, Myelomonocytic, Chronic, Leukemia, Myeloid, Acute
- Interventions
- Azacitidine, Pevonedistat
- First posted
- 2017-08-31
- Last updated
- 2025-10-29
- Other registries' IDs
- eudract:2017-000318-40
- Results first posted
- 2022-09-22
Source ClinicalTrials.gov
Registered outcomes29
Each outcome the trial registered, primary first, in ClinicalTrials.gov's words.
| List | Outcome | Time frame | Description |
|---|---|---|---|
| Primary | Event-Free Survival (EFS) | From randomization until transformation to acute myeloid leukemia, or death due to any cause: up to approximately 42 months | EFS was defined as the time from randomization to the date of an EFS event. An EFS event was defined as death or transformation to acute myelogenous leukemia (AML) (World Health Organization \[WHO\] classification as a participant having greater than 20 % blasts in the blood or marrow and an increase of blast count by 50%), whichever event occurred first, in participants with myelodysplastic syndromes (MDS) or chronic myelomonocytic leukemias (CMML). An EFS event was defined as death in participants with low-blast AML. |
| Secondary | Overall Survival (OS) | Up to approximately 6.9 years | Overall survival was defined as the time from randomization to death from any cause. |
| Secondary | Kaplan-Meier Estimates of Six-Month Survival Rate | Month 6 | Kaplan-Meier estimates for the probability (expressed as a percentage) of participants that survived at the end of Month 6 from randomization are presented. |
| Secondary | Kaplan-Meier Estimates of One-Year Survival Rate | Year 1 | Kaplan-Meier estimates for the probability (expressed as a percentage) of participants that survived at the end of the first year from randomization are presented. |
| Secondary | Thirty-Day Mortality Reported as Number of Participants Who Died Up to Day 30 | Up to Day 30 | 30-day mortality was defined as number of participants who died within 30 days from the first dose of study drug. |
| Secondary | Sixty-Day Mortality Reported as Number of Participants Who Died Up to Day 60 | Up to Day 60 | 60-day mortality was defined as number of participants who died within 60 days from the first dose of study drug. |
| Secondary | Time to Acute Myelogenous Leukemia (AML) Transformation in Higher-Risk Myelodysplastic Syndromes (HR MDS), Higher-Risk Chronic Myelomonocytic Leukemias (HR CMML) and HR MDS/CMML Participants | From randomization until transformation to AML (up to approximately 42 months) | Time to AML transformation in HR MDS and CMML participants was defined as time from randomization to documented AML transformation as determined by the independent review committee (IRC) assessment. Participants who died before progression to AML were censored. Transformation to AML was defined, according to WHO classification, as a participant having 20% blasts in the blood or marrow and increase of blast count by 50%. |
| Secondary | Number of Participants With Complete Remission (CR) and CR+ Complete Remission With Incomplete Blood Count Recovery (CRi) | From randomization until CR (up to approximately 42 months) | CR for HR MDS or CMML is defined as \<=5% myeloblasts with normal maturation of all cell lines in the bone marrow, and greater than or equal to \>=11 gram per deciliter (g/dL) hemoglobin (Hgb),\>=100\*10\^9/liter (/L) platelets (pl),\>=1.0\*10\^9/L neutrophils and 0% blasts in peripheral blood. CR for low-blast AML: morphologic leukemia-free state, neutrophils of more than 1.0\*10\^9/L and pl of \>=100\*10\^9/L, transfusion independence, and no residual evidence of extramedullary leukemia. CR with incomplete blood count recovery (CRi) for low-blast AML: participants fulfill all of the criteria for CR except for residual neutropenia (\<1.0\*10\^9/L) or thrombocytopenia (pl\<100\*10\^9/L). |
| Secondary | Number of Participants With CR and Marrow CR | From randomization until CR or marrow CR (up to approximately 42 months) | Disease responses for HR MDS or CMML are based on the International Working Group (IWG) Response Criteria for MDS. CR for HR MDS or CMML is defined as \<=5% myeloblasts with normal maturation of all cell lines in the bone marrow, and \>=11 g/dL Hgb, \>=100\*10\^9/L platelets (pl), \>=1.0\*10\^9/L neutrophils and 0% blasts in peripheral blood. Marrow CR: Bone marrow: \<=5% myeloblasts and decrease by \>=50% over pretreatment. |
| Secondary | Number of Participants With CR, Partial Remission (PR) and Hematologic Improvement (HI) | From randomization until, CR, PR or HI (up to approximately 42 months) | Disease responses for HR MDS/CMML based on Modified IWG Response Criteria for MDS. CR: \<=5% myeloblasts with normal maturation of all bone marrow cell lines, \>=11 g/dL Hgb, \>=100\*10\^9/L pl, \>=1.0\*10\^9/L neutrophils,0% blasts in peripheral blood. Marrow CR: Bone marrow: \<=5% myeloblasts and decrease by \>=50% over pretreatment. PR: all CR criteria met except bone marrow blasts \>=50% decrease over pretreatment but still \>5%. HI: Hgb increase \>=1.5 g/dL if \<11 g/dL; pl increase \>=30\*10\^9/L if baseline\>20\*10\^9/L or increase from \<20\*10\^9/L to \>20\*10\^9/L and by at least 100%; neutrophil increase by 100% and absolute increase of \>0.5\*10\^9/L if baseline \<1.0\*10\^9/L. |
1 to 10 of 29Source ClinicalTrials.gov
See all 29 registered outcomesOutcomes29
Each outcome the trial posted results for, in ClinicalTrials.gov's words.
| Type | Outcome | Time frame | Population | Units | Measured as |
|---|---|---|---|---|---|
| PRIMARY | Event-Free Survival (EFS) | From randomization until transformation to acute myeloid leukemia, or death due to any cause: up to approximately 42 months | ITT Population included all participants who were randomized. | months | MEDIAN |
| SECONDARY | Overall Survival (OS) | Up to approximately 6.9 years | ITT Population included all participants who were randomized. | months | MEDIAN |
| SECONDARY | Kaplan-Meier Estimates of Six-Month Survival Rate | Month 6 | ITT Population included all participants who were randomized. Overall number analyzed is the number of participants with data available for analyses. | percentage probability | NUMBER |
| SECONDARY | Kaplan-Meier Estimates of One-Year Survival Rate | Year 1 | ITT Population included all participants who were randomized. Overall number analyzed is the number of participants with data available for analyses. | percentage probability | NUMBER |
| SECONDARY | Thirty-Day Mortality Reported as Number of Participants Who Died Up to Day 30 | Up to Day 30 | Safety Population included all enrolled participants who received at least 1 dose of azacitidine alone or pevonedistat + azacitidine. | Participants | COUNT_OF_PARTICIPANTS |
| SECONDARY | Sixty-Day Mortality Reported as Number of Participants Who Died Up to Day 60 | Up to Day 60 | Safety Population included all enrolled participants who received at least 1 dose of azacitidine alone or pevonedistat + azacitidine. | Participants | COUNT_OF_PARTICIPANTS |
| SECONDARY | Time to Acute Myelogenous Leukemia (AML) Transformation in Higher-Risk Myelodysplastic Syndromes (HR MDS), Higher-Risk Chronic Myelomonocytic Leukemias (HR CMML) and HR MDS/CMML Participants | From randomization until transformation to AML (up to approximately 42 months) | ITT Population included all participants who were randomized. Overall number analyzed is the number of participants with data available for analyses. Number analyzed is the number of participants with data available for analysis for the given category. | months | MEDIAN |
| SECONDARY | Number of Participants With Complete Remission (CR) and CR+ Complete Remission With Incomplete Blood Count Recovery (CRi) | From randomization until CR (up to approximately 42 months) | Response-Evaluable Population (REP) included all participants who received at least 1 dose of study drug and had a Baseline and at least 1 postbaseline disease assessment. | Participants | COUNT_OF_PARTICIPANTS |
| SECONDARY | Number of Participants With CR and Marrow CR | From randomization until CR or marrow CR (up to approximately 42 months) | REP included all participants who received at least 1 dose of study drug and had a Baseline and at least 1 postbaseline disease assessment. | Participants | COUNT_OF_PARTICIPANTS |
| SECONDARY | Number of Participants With CR, Partial Remission (PR) and Hematologic Improvement (HI) | From randomization until, CR, PR or HI (up to approximately 42 months) | REP included all participants who received at least 1 dose of study drug and had a Baseline and at least 1 postbaseline disease assessment. | Participants | COUNT_OF_PARTICIPANTS |
1 to 10 of 29Source ClinicalTrials.gov
See all 29 outcomesResults by group134
Each measurement the trial posted, group by group, in the words and numbers it posted.
| Outcome | Group | Category | Value | Spread | Units |
|---|---|---|---|---|---|
| Event-Free Survival (EFS) | Azacitidine 75 mg/m^2 | 15.7 | 95% Confidence Interval 14.42 to 19.68 | months | |
| Event-Free Survival (EFS) | Pevonedistat 20 mg/m^2 + Azacitidine 75 mg/m^2 | 17.7 | 95% Confidence Interval 13.63 to 20.24 | months | |
| Overall Survival (OS) | Azacitidine 75 mg/m^2 | 16.8 | 95% Confidence Interval 14.92 to 20.11 | months | |
| Overall Survival (OS) | Pevonedistat 20 mg/m^2 + Azacitidine 75 mg/m^2 | 20.3 | 95% Confidence Interval 17.97 to 22.60 | months | |
| Kaplan-Meier Estimates of Six-Month Survival Rate | Azacitidine 75 mg/m^2 | 0.825 | 95% Confidence Interval 0.767 to 0.869 | percentage probability | |
| Kaplan-Meier Estimates of Six-Month Survival Rate | Pevonedistat 20 mg/m^2 + Azacitidine 75 mg/m^2 | 0.810 | 95% Confidence Interval 0.752 to 0.856 | percentage probability | |
| Kaplan-Meier Estimates of One-Year Survival Rate | Azacitidine 75 mg/m^2 | 0.693 | 95% Confidence Interval 0.626 to 0.751 | percentage probability | |
| Kaplan-Meier Estimates of One-Year Survival Rate | Pevonedistat 20 mg/m^2 + Azacitidine 75 mg/m^2 | 0.646 | 95% Confidence Interval 0.578 to 0.706 | percentage probability | |
| Thirty-Day Mortality Reported as Number of Participants Who Died Up to Day 30 | Azacitidine 75 mg/m^2 | 6 | Participants | ||
| Thirty-Day Mortality Reported as Number of Participants Who Died Up to Day 30 | Pevonedistat 20 mg/m^2 + Azacitidine 75 mg/m^2 | 5 | Participants |
1 to 10 of 134Source ClinicalTrials.gov
See all 134 results by groupParticipant flow8
How many started, completed or left each group, period by period.
| Period | Milestone | Group | Participants | Units counted |
|---|---|---|---|---|
| Overall Study | STARTED | Azacitidine 75 mg/m^2 | 227 | |
| Overall Study | STARTED | Pevonedistat 20 mg/m^2 + Azacitidine 75 mg/m^2 | 227 | |
| Overall Study | Safety Population | Azacitidine 75 mg/m^2 | 220 | |
| Overall Study | Safety Population | Pevonedistat 20 mg/m^2 + Azacitidine 75 mg/m^2 | 223 | |
| Overall Study | COMPLETED | Azacitidine 75 mg/m^2 | 195 | |
| Overall Study | COMPLETED | Pevonedistat 20 mg/m^2 + Azacitidine 75 mg/m^2 | 199 | |
| Overall Study | NOT COMPLETED | Azacitidine 75 mg/m^2 | 32 | |
| Overall Study | NOT COMPLETED | Pevonedistat 20 mg/m^2 + Azacitidine 75 mg/m^2 | 28 |
Source ClinicalTrials.gov
Adverse events588
Each adverse event the trial posted, group by group: the participants affected out of those at risk.
| Type | Event | Organ system | Group | Affected | At risk | Events |
|---|---|---|---|---|---|---|
| other | Abdominal pain | Gastrointestinal disorders | Azacitidine 75 mg/m^2 | 15 | 220 | |
| other | Abdominal pain | Gastrointestinal disorders | Pevonedistat 20 mg/m^2 + Azacitidine 75 mg/m^2 | 22 | 223 | |
| other | Abdominal pain upper | Gastrointestinal disorders | Azacitidine 75 mg/m^2 | 12 | 220 | |
| other | Abdominal pain upper | Gastrointestinal disorders | Pevonedistat 20 mg/m^2 + Azacitidine 75 mg/m^2 | 13 | 223 | |
| other | Abnormal loss of weight | Metabolism and nutrition disorders | Azacitidine 75 mg/m^2 | 12 | 220 | |
| other | Abnormal loss of weight | Metabolism and nutrition disorders | Pevonedistat 20 mg/m^2 + Azacitidine 75 mg/m^2 | 7 | 223 | |
| other | Alanine aminotransferase increased | Investigations | Azacitidine 75 mg/m^2 | 11 | 220 | |
| other | Alanine aminotransferase increased | Investigations | Pevonedistat 20 mg/m^2 + Azacitidine 75 mg/m^2 | 19 | 223 | |
| other | Anaemia | Blood and lymphatic system disorders | Azacitidine 75 mg/m^2 | 82 | 220 | |
| other | Anaemia | Blood and lymphatic system disorders | Pevonedistat 20 mg/m^2 + Azacitidine 75 mg/m^2 | 78 | 223 |
1 to 10 of 588Source ClinicalTrials.gov
See all 588 adverse eventsAdverse event totals6
The totals the trial posted for each group.
| Total | Group | Affected | At risk |
|---|---|---|---|
| Total, all-cause mortality | Azacitidine 75 mg/m^2 | 153 | 220 |
| Total, all-cause mortality | Pevonedistat 20 mg/m^2 + Azacitidine 75 mg/m^2 | 150 | 223 |
| Total, other adverse events | Azacitidine 75 mg/m^2 | 207 | 220 |
| Total, other adverse events | Pevonedistat 20 mg/m^2 + Azacitidine 75 mg/m^2 | 210 | 223 |
| Total, serious adverse events | Azacitidine 75 mg/m^2 | 145 | 220 |
| Total, serious adverse events | Pevonedistat 20 mg/m^2 + Azacitidine 75 mg/m^2 | 156 | 223 |
Source ClinicalTrials.gov
Papers1
The papers the trial lists on ClinicalTrials.gov.
| PMID | Listed as |
|---|---|
| 35728048 | DERIVED |
Source PubMed
Grants0
The grants NIH RePORTER links to the trial, newest funded first: NIH's, and some of AHRQ's, CDC's, FDA's and VA's. Each shows its title, principal investigators, organization and funder in its newest year.
None in this release.
Trial comparisons13
Comparisons of the trial's two groups, calculated by ConductScience from the counts it posted.
| Comparison | Source |
|---|---|
| Azacitidine 75 mg/m^2 vs Pevonedistat 20 mg/m^2 + Azacitidine 75 mg/m^2: Number of Participants With CR and Marrow CR, PR and Hematologic Improvement (HI) | Trial comparisons |
| Azacitidine 75 mg/m^2 vs Pevonedistat 20 mg/m^2 + Azacitidine 75 mg/m^2: Number of Participants With at Least 1 Inpatient Hospital Admissions Related to HR MDS, CMML or Low-blast AML | Trial comparisons |
| Azacitidine 75 mg/m^2 vs Pevonedistat 20 mg/m^2 + Azacitidine 75 mg/m^2: Number of Participants With Overall Response 2 (OR2) | Trial comparisons |
| Azacitidine 75 mg/m^2 vs Pevonedistat 20 mg/m^2 + Azacitidine 75 mg/m^2: Number of Participants With CR and Marrow CR and PR | Trial comparisons |
| Azacitidine 75 mg/m^2 vs Pevonedistat 20 mg/m^2 + Azacitidine 75 mg/m^2: Number of Participants With CR, Partial Remission (PR) and Hematologic Improvement (HI) | Trial comparisons |
| Azacitidine 75 mg/m^2 vs Pevonedistat 20 mg/m^2 + Azacitidine 75 mg/m^2: Number of Participants With Hematologic Improvement (HI) | Trial comparisons |
| Azacitidine 75 mg/m^2 vs Pevonedistat 20 mg/m^2 + Azacitidine 75 mg/m^2: Sixty-Day Mortality Reported as Number of Participants Who Died Up to Day 60 | Trial comparisons |
| Azacitidine 75 mg/m^2 vs Pevonedistat 20 mg/m^2 + Azacitidine 75 mg/m^2: Thirty-Day Mortality Reported as Number of Participants Who Died Up to Day 30 | Trial comparisons |
| Azacitidine 75 mg/m^2 vs Pevonedistat 20 mg/m^2 + Azacitidine 75 mg/m^2: Number of Participants With CR and Marrow CR | Trial comparisons |
| Azacitidine 75 mg/m^2 vs Pevonedistat 20 mg/m^2 + Azacitidine 75 mg/m^2: deaths from any cause | Trial comparisons |
1 to 10 of 13
See all 13 trial comparisonsTests0
The ConductCognition tests this trial's registered outcomes name, as ScienceGraph matched them in trial-tests-2026-11-12-0.2.1.
None in this release.
Data dates
The day each source was copied for this release.
Sources 3
- ClinicalTrials.gov's posted results, through CTTI's AACTFreely available. Acknowledgement requested
- ClinicalTrials.govNo license stated
- NIH RePORTER's clinical studies and project filesPublic domain
Each source's terms
- ClinicalTrials.gov's posted results, through CTTI's AACTClinicalTrials.gov data via Aggregate Analysis of ClinicalTrials.gov (AACT), CTTI. CTTI makes its materials freely available and requests acknowledgement. https://aact.ctti-clinicaltrials.org/documentation/299
- ClinicalTrials.govnone stated
- NIH RePORTER's clinical studies and project filesPublic domain (NIH RePORTER)
ClinicalTrials.gov's data carry an international copyright outside the United States: https://clinicaltrials.gov/about-site/terms-conditions.
For software
Read this trial from software.
The record and each of its lists are JSON, twenty rows a page. No key.
GET https://conductscience.org/api/trials/v1/NCT03268954
GET https://conductscience.org/api/trials/v1/NCT03268954/registered?page=2