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| ID | Type | Description | Link |
|---|---|---|---|
| U1111-1169-6540 | Registry Identifier | WHO | |
| 2015-000221-37 | EudraCT Number | ||
| REec-2016-2145 | Registry Identifier | REec | |
| Pevonedistat-2001CTID | Other Identifier | Israel |
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The purpose of this study is to evaluate the efficacy and safety of pevonedistat plus azacitidine versus single-agent azacitidine in participants with HR-MDS or CMML, or low-blast AML.
The drug being tested in this study is called pevonedistat. Pevonedistat is being tested to treat people with MDS or CMML, or low-blast AML as a combination treatment with azacitidine. This study will look at the overall survival, event free survival and response to treatment in people who take pevonedistat and azacitidine when compared to people who take single-agent azacitidine.
The study will enroll 120 participants. Once enrolled, participants will be randomly assigned (by chance, like flipping a coin) to one of the two treatment groups in 28-day treatment cycles:
All participants will receive azacitidine via intravenous or subcutaneous route. Participants randomized to the combination arm will also receive pevonedistat intravenous infusion.
This multi-center trial will be conducted worldwide. The overall time to participate in this study is approximately 44 months. Participants will attend the end-of-treatment visit 30 days after the last dose of study drug or before the start of subsequent anti-neoplastic therapy if that occurs sooner. Participants will enter event-free survival follow-up or response follow-up (study visits every 3 months) if their disease has not transformed to AML (for participants with HR MDS or CMML) or progressed (for participants with low-blast AML), and they have not started subsequent therapy. Participants will also enter overall survival follow-up (contacted every 3 months to document subsequent therapies and survival status).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Azacitidine 75 mg/m^2 | Active Comparator | Azacitidine 75 mg/m^2, infusion, intravenously or subcutaneously, on Day 1 through Day 5, 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). |
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| Azacitidine 75 mg/m^2 + Pevonedistat 20 mg/m^2 | Experimental | Azacitidine 75 mg/m^2, infusion, intravenously or subcutaneously, on Day 1 through Day 5, 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). |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Azacitidine | Drug | Azacitidine intravenous or subcutaneous formulation. |
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| Measure | Description | Time Frame |
|---|---|---|
| Overall Survival (OS) | 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. The Kaplan Meier estimates was used for the analysis. | From date of randomization until death (up to 3 years and 5 months) |
| Measure | Description | Time Frame |
|---|---|---|
| Event-Free Survival (EFS) | 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. The Kaplan-Meier estimate was used for the analysis. |
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Inclusion Criteria:
Male or female participants 18 years or older.
Morphologically confirmed diagnosis of MDS or nonproliferative CMML (that is, with white blood cells [WBC] <20,000 per microliter [/mcL]) or low blast AML based on 1 of the following:
French American British (FAB) Classifications:
OR
WHO Classifications:
For MDS and CMML participants, prognostic risk category, based on the Revised International Prognostic Scoring System (IPSS R), of:
Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
Clinical laboratory values within the following parameters (repeat within 3 days before the first dose of study drug if laboratory values used for randomization were obtained more than 3 days before the first dose of study drug):
For CMML participants: WBC count <20,000/mcL before administration of the first dose of study drug on Cycle 1 Day 1; participants must have been off hydroxyurea for at least 1 week prior to WBC count assessment.
Ability to undergo the study required bone marrow sample collection procedures.
Suitable venous access for the study required blood sampling (that is, including pharmacokinetic (PK) and biomarker sampling).
Female participants who:
Male participants, even if surgically sterilized (that is, status postvasectomy), who:
Voluntary written consent must be given before performance of any study related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the participant at any time without prejudice to future medical care.
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Medical Director | Millennium Pharmaceuticals, Inc. | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Alabama | Birmingham | Alabama | 35233 | United States | ||
| Greenville Health System |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 33483617 | Derived | Sekeres MA, Watts J, Radinoff A, Sangerman MA, Cerrano M, Lopez PF, Zeidner JF, Campelo MD, Graux C, Liesveld J, Selleslag D, Tzvetkov N, Fram RJ, Zhao D, Bell J, Friedlander S, Faller DV, Ades L. Randomized phase 2 trial of pevonedistat plus azacitidine versus azacitidine for higher-risk MDS/CMML or low-blast AML. Leukemia. 2021 Jul;35(7):2119-2124. doi: 10.1038/s41375-021-01125-4. Epub 2021 Jan 22. No abstract available. |
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Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
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IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.
Participants diagnosed with myelomonocytic, and myelogenous leukemia were randomized into two groups in 1:1 ratio to receive single-agent azacitidine or azacitidine + pevonedistat.
Participants took part in the study at 45 investigative sites in the United States [US], Canada, Belgium, Bulgaria, Czech Republic, Germany, France, Israel, Italy, Spain, and Ireland from 14 April 2016 to 23 July 2021.
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| ID | Title | Description |
|---|---|---|
| FG000 | Azacitidine 75 mg/m^2 | Azacitidine 75 mg/m^2, infusion, intravenously or subcutaneously, on Day 1 through Day 5, 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). |
| FG001 |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Jul 27, 2018 | Aug 31, 2020 |
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| Pevonedistat | Drug | Pevonedistat intravenous infusion. |
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| From date of randomization until transformation to AML, or death due to any cause (up to approximately 5 years) |
| Six-month Survival Rate | Kaplan-Meier estimate of probability of OS at the end of the month 6 from randomization. | Month 6 |
| One-year Survival Rate | Kaplan-Meier estimate of probability of OS at the end of the first year from randomization. | Month 12 |
| Time to AML Transformation in HR MDS or CMML Participants | Time to AML transformation in HR MDS and CMML participants is defined as time from randomization to documented AML transformation. Participants without documented AML transformation at the time of the analysis are censored at the date of the last assessment. Participants who died before progression to AML are censored at the date of death. 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%. | From date of randomization until transformation to AML (up to approximately 5 years) |
| Percentage of Participants With Complete Remission (CR) | 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: <= 5% myeloblasts with normal maturation of all cell lines in the bone marrow, and >= 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). The percentages are rounded off to report the nearest whole numbers. | From date of randomization until CR (up to approximately 5 years) |
| Percentage of Participants With CR and Partial Remission (PR) | 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. The percentages are rounded off to report the nearest whole numbers. | From date of randomization until CR and PR (up to approximately 5 years) |
| Percentage of Participants With Overall Response | 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. The percentages are rounded off to report the nearest whole numbers. | From date of randomization until CR, PR, or hematologic improvement (HI) (up to approximately 5 years) |
| Percentage of Participants With CR in Low-blast AML | 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). The percentages are rounded off to report the nearest whole numbers. | From date of randomization until CR (up to approximately 5 years) |
| Percentage of Participants With CR by Cycle 4 | 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). The percentages are rounded off to report the nearest whole numbers. | From date of randomization until CR by Cycle 4 (cycle length is equal to [=] 28 days) |
| Percentage of Participants With CR and PR by Cycle 4 | 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. The percentages are rounded off to report the nearest whole numbers. | From date of randomization until CR and PR, by Cycle 4 (cycle length=28 days) |
| Percentage of Participants With Overall Response by Cycle 4 | 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. The percentages are rounded off to report the nearest whole numbers. | From date of randomization until CR, PR or HI, by Cycle 4 (cycle length=28 days) |
| Percentage of Participants With CR in Low-blast AML by Cycle 4 | 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). The percentages are rounded off to report the nearest whole numbers. | From the date of randomization until CR by Cycle 4 (cycle length=28 days) |
| Duration of Complete Remission (CR) | Duration of CR is first documented CR to the first documentation of PD or relapse from CR (participants with low-blast AML) or relapse after CR or PR (participants with HR MDS/CMML). Disease responses for HR MDS or CMML are based on the Modified IWG Response Criteria for MDS and for low-blast AML on the Revised IWG Response Criteria for AML.CR for HR MDS or CMML≤5% myeloblasts with normal maturation of all cell lines in the bone marrow,≥11 g/dL Hgb,≥100*10^9/L pl,≥1.0*10^9/L neutrophils;0% blasts in peripheral blood.CR for low-blast AML:morphologic leukemia-free state,neutrophils of<1.0*10^9/L;pl of≥100*10^9/L,transfusion independence,no residual evidence of extramedullary leukemia.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). | From date of randomization until CR (up to approximately 5 years) |
| Duration of Complete Remission (CR) and Partial Remission (PR) | Duration of CR is first documented CR to the first documentation of PD or relapse from CR (participants with low-blast AML). 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. | From date of randomization until CR or PR (up to approximately 5 years) |
| Duration of Overall Response | Duration of OR: response to first documentation of PD or relapse from CR for low-blast AML or relapse after CR or PR for HR MDS/CMML. Disease responses(HR MDS/CMML): modified IWG criteria for MDS;low-blast AML: revised IWG criteria for AML.Overall response(HR MDS/CMML)=CR,PR/HI,LB AML=CR+ Cri+PR.HR MDS/CMML-CR:≤5%myeloblasts with normal maturation of 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. | From date of randomization until CR, PR or HI (up to approximately 5 years) |
| Duration of Complete Remission (CR) in Low-blast AML | 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). | From date of randomization until CR (up to approximately 5 years) |
| Time to First CR or PR | 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. | From date of randomization until CR or PR (up to approximately 5 years) |
| Time to Subsequent Therapy | 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 did not be counted as receiving subsequent therapy. | From date of randomization up to approximately 5 years |
| Percentage of Participants With Red Blood Cells (RBCs) and Platelet-transfusion Independence | A participant was defined as RBC or platelet-transfusion independent if he/she received no RBC or platelet transfusions for a period of at least 8 weeks before the first dose of study drug through 30 days after the last dose of any study drug. Rate of transfusion independence was defined as number of participants who became transfusion independent divided by the number of participants who were transfusion dependent at Baseline. | 8 weeks before randomization through 30 days after last dose of any study drug (up to approximately 5 years and 3 months) |
| Percentage of Participants With at Least 1 Inpatient Hospital Admissions Related to HR MDS, CMML or Low-blast AML | Inpatient hospital admission data was 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 occurred 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%. Percentage of participants was calculated as the total number of events divided by the total number of subject-years in each group. | From date of randomization until transformation to AML or until initiation of subsequent therapy (up to approximately 5 years) |
| Time to Progressive Disease (PD), Relapse, or Death | 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. | From date of randomization until PD, relapse or death (up to approximately 5 years) |
| Number of Participants Reporting One or More Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. A SAE was defined as any untoward medical occurrence that: 1) results in death, 2) is life-threatening, 3) requires inpatient hospitalization or prolongation of existing hospitalization, 4) results in persistent or significant disability/incapacity, 5) leads to a congenital anomaly/birth defect in the offspring of the participant or 6) is an medically important event that satisfies any of the following: a) May require intervention to prevent items 1 through 5 above. b) May expose the participant to danger, even though the event is not immediately life threatening or fatal or does not result in hospitalization. A TEAE was defined as any adverse event occurring after the start of pevonedistat administration of the treatment period. | From date of first dose up to 30 days after administration of the last dose of any study drug (up to approximately 5 years) |
| Number of Participants in the Safety Analysis Population With Clinically Significant Laboratory Abnormalities Reported as TEAEs | Laboratory assessments included clinical chemistry, hematology, and urinalysis. | From date of first dose up to 30 days after administration of the last dose of any study drug (up to approximately 5 years) |
| Number of Participants With Change From Baseline Values in Eastern Cooperative Oncology Group (ECOG) Performance Status | 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). | From date of first dose up to 30 days after administration of the last dose of any study drug (up to approximately 5 years) |
| Number of Participants in the Safety Analysis Population With Clinically Significant Change From Baseline in Electrocardiogram (ECG) Values Reported as TEAEs | ECG assessments included QT, QRS duration, PR interval, ventricular rate, QTcB, QTcF. | From date of first dose up to 30 days after administration of the last dose of any study drug (up to approximately 5 years) |
| Number of Participants in the Safety Analysis Population With Clinically Significant Change From Baseline Values in Vital Signs Reported as TEAEs | Vital signs assessments included diastolic and systolic blood pressure, heart rate, and body temperature. | From date of first dose up to 30 days after administration of the last dose of any study drug (up to approximately 5 years) |
| Little Rock |
| Arkansas |
| 72201 |
| United States |
| UC San Diego Moores Cancer Center | La Jolla | California | 92093 | United States |
| Compassionate Cancer Care Medical Group Incorporated | Riverside | California | 92501 | United States |
| Rocky Mountain Cancer Centers | Aurora | Colorado | 80012 | United States |
| Smilow Cancer Center at Yale New Haven Hospital | New Haven | Connecticut | 06510 | United States |
| University of Miami Miller School of Medicine | Miami | Florida | 33136 | United States |
| H Lee Moffitt Cancer Center and Research Institute | Tampa | Florida | 33612 | United States |
| University of Chicago Medical Center | Chicago | Illinois | 60637 | United States |
| Johns Hopkins University | Baltimore | Maryland | 21287 | United States |
| San Juan Oncology Associates | Farmington | New Mexico | 87401 | United States |
| Monter Cancer Center | Lake Success | New York | 11042 | United States |
| Weill Cornell Medical College | New York | New York | 10021 | United States |
| Columbia University Medical Center | New York | New York | 10032 | United States |
| University of Rochester Medical Center | Rochester | New York | 14603 | United States |
| University of North Carolina at Chapel Hill | Chapel Hill | North Carolina | 27599 | United States |
| Cleveland Clinic | Cleveland | Ohio | 44195 | United States |
| Cancer Care Center of South Texas | New Braunfels | Texas | 78130 | United States |
| Nebraska Cancer Specialists | The Woodlands | Texas | 77380 | United States |
| Texas Oncology - Waco, TX | Tyler | Texas | 76712 | United States |
| University of Virginia | Charlottesville | Virginia | 22903 | United States |
| Medical Oncology Associates | Spokane | Washington | 99208 | United States |
| Yakima Valley Memorial Hospital | Yakima | Washington | 98902 | United States |
| AZ Sint-Jan AV | Bruges | West-Vlaanderen | 8400 | Belgium |
| Grand Hopital de Charleroi asbl | Charleroi | 6000 | Belgium |
| Cliniques Universitaires UCL de Mont-Godinne | Yvoir | 5500 | Belgium |
| University Multiprofile Hospital for Active Treatment Sv Ivan Rilski EAD | Sofia | 1113 | Bulgaria |
| Specialized Hospital for Active Treatment of Haematological Diseases - Sofia | Sofia | 1756 | Bulgaria |
| University Multi-Profile Hospital for Active Treatment Dr Georgi Stranski | Sofia | 1756 | Bulgaria |
| Sunnybrook Health Science Centre | Toronto | Ontario | M4N 3M5 | Canada |
| Princess Margaret Hospital | Toronto | Ontario | M5G 2M9 | Canada |
| Fakultni Nemocnice Brno | Brno | 625 00 | Czechia |
| Fakultni Nemocnice Kralovske Vinohrady | Prague | 10034 | Czechia |
| CHU de GRENOBLE | Grenoble | 38700 | France |
| CHRU Lille | Lille | 59000 | France |
| Hopital Saint Louis | Paris | 75010 | France |
| Marien Hospital Akademisches Lehrkrankenhaus | Düsseldorf | 40479 | Germany |
| Universitatsklinikum Ulm | Ulm | 89081 | Germany |
| Tallaght Hospital | Dublin | 24 | Ireland |
| University Hospital Galway | Galway | Ireland |
| Shaare Zedek Medical Center | Jerusalem | 9103102 | Israel |
| ZIV Medical Center | Safed | 13100 | Israel |
| Tel Aviv Sourasky Medical Center | Tel Aviv | 13100 | Israel |
| Azienda Ospedaliero Universitaria Di Bologna - Policlinico S Orsola Malpighi | Bologna | 40138 | Italy |
| Azienda Ospedaliera Universitaria Careggi | Florence | 50139 | Italy |
| Azienda Ospedaliera Bianchi Melacrino Morelli | Reggio Calabria | 89100 | Italy |
| Azienda Ospedaliero Universitaria San Giovanni Battista Di Torino | Torino | 10126 | Italy |
| Zuyderland Medisch Centrum | Sittard | 6162 BG | Netherlands |
| Hospital Universitario Son Espases | Palma de Mallorca | Balearic Islands | 7010 | Spain |
| Hospital Universitario Quironsalud Madrid | Pozuelo de Alarcón | Madrid | 28223 | Spain |
| Hospital Universitario Germans Trias i Pujol | Badalona | 8916 | Spain |
| ICO I'Hospitalet Hospital Duran i Reynals Instituto Catalan de Oncologia de Hospitalet (ICO) | Barcelona | 08908 | Spain |
| Hospital Clinic de Barcelona | Barcelona | 8036 | Spain |
| Hospital General Universitario Gregorio Maranon | Madrid | 28007 | Spain |
| Hospital Universitario La Paz | Madrid | 28046 | Spain |
| Hospital Regional Universitario de Malaga - Hospital Universitario Virgen de la Victoria | Málaga | 29010 | Spain |
| Hospital Universitario de Salamanca | Salamanca | 37007 | Spain |
| Hospital Clinico Universitario de Valencia | Valencia | 46010 | Spain |
| Hospital Universitari i Politecnic La Fe de Valencia | Valencia | 46026 | Spain |
| Azacitidine 75 mg/m^2 + Pevonedistat 20 mg/m^2 |
Azacitidine 75 mg/m^2, infusion, intravenously or subcutaneously, on Day 1 through Day 5, 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). |
| Response Evaluable Population (REP) | Response Evaluable Population (REP) included all participants who received at least 1 dose of study drug, have a disease assessment at baseline, and at least 1 post baseline disease assessment. |
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| NOT COMPLETED |
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Intent-to-treat (IIT) population was defined as all participants who were randomized.
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Azacitidine 75 mg/m^2 | Azacitidine 75 mg/m^2, infusion, intravenously or subcutaneously, on Day 1 through Day 5, 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). |
| BG001 | Azacitidine 75 mg/m^2 + Pevonedistat 20 mg/m^2 | Azacitidine 75 mg/m^2, infusion, intravenously or subcutaneously, on Day 1 through Day 5, 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). |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
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| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
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| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Region of Enrollment | Count of Participants | Participants |
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| Height | Mean | Standard Deviation | centimeter (cm) |
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| Weight | Mean | Standard Deviation | kilogram (kg) |
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| Body Surface Area | Body surface area was defined as [height (cm) × weight (kg)/3600]½ based on height and weight collected at baseline. | Mean | Standard Deviation | square meter (m^2) |
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| 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 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Primary | Overall Survival (OS) | 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. The Kaplan Meier estimates was used for the analysis. | ITT Population was defined as all participants who were randomized. | Posted | Median | 95% Confidence Interval | months | From date of randomization until death (up to 3 years and 5 months) |
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| Secondary | Event-Free Survival (EFS) | 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. The Kaplan-Meier estimate was used for the analysis. | ITT Population was defined as all participants who were randomized. | Posted | Median | 95% Confidence Interval | months | From date of randomization until transformation to AML, or death due to any cause (up to approximately 5 years) |
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| Secondary | Six-month Survival Rate | Kaplan-Meier estimate of probability of OS at the end of the month 6 from randomization. | ITT Population was defined as all participants who were randomized. Overall number analyzed are the number of participants with data available for analyses. | Posted | Number | 95% Confidence Interval | survival probability | Month 6 |
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| Secondary | One-year Survival Rate | Kaplan-Meier estimate of probability of OS at the end of the first year from randomization. | ITT Population was defined as all participants who were randomized. Overall number analyzed are the number of participants with data available for analyses. | Posted | Number | 95% Confidence Interval | survival probability | Month 12 |
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| Secondary | Time to AML Transformation in HR MDS or CMML Participants | Time to AML transformation in HR MDS and CMML participants is defined as time from randomization to documented AML transformation. Participants without documented AML transformation at the time of the analysis are censored at the date of the last assessment. Participants who died before progression to AML are censored at the date of death. 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%. | ITT Population was defined as all participants who were randomized. Overall number of participants analyzed is the number of participants with data available for analyses. | Posted | Median | 95% Confidence Interval | months | From date of randomization until transformation to AML (up to approximately 5 years) |
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| Secondary | Percentage of Participants With Complete Remission (CR) | 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: <= 5% myeloblasts with normal maturation of all cell lines in the bone marrow, and >= 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). The percentages are rounded off to report the nearest whole numbers. | 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. | Posted | Number | percentage of participants | From date of randomization until CR (up to approximately 5 years) |
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| Secondary | Percentage of Participants With CR and Partial Remission (PR) | 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. The percentages are rounded off to report the nearest whole numbers. | REP included all participants who received at least 1 dose of study drug and had a Baseline and at least 1 postbaseline disease assessment. | Posted | Number | percentage of participants | From date of randomization until CR and PR (up to approximately 5 years) |
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| Secondary | Percentage of Participants With Overall Response | 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. The percentages are rounded off to report the nearest whole numbers. | REP included all participants who received at least 1 dose of study drug and had a Baseline and at least 1 postbaseline disease assessment. | Posted | Number | percentage of participants | From date of randomization until CR, PR, or hematologic improvement (HI) (up to approximately 5 years) |
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| Secondary | Percentage of Participants With CR in Low-blast AML | 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). The percentages are rounded off to report the nearest whole numbers. | REP included all participants who received at least 1 dose of study drug and had a Baseline and at least 1 postbaseline disease assessment. Overall number analyzed are the number of participants with data available for analyses. | Posted | Number | percentage of participants | From date of randomization until CR (up to approximately 5 years) |
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| Secondary | Percentage of Participants With CR by Cycle 4 | 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). The percentages are rounded off to report the nearest whole numbers. | REP included all participants who received at least 1 dose of study drug and had a Baseline and at least 1 postbaseline disease assessment. Overall number analyzed is the number of participants with data available for analyses. | Posted | Number | percentage of participants | From date of randomization until CR by Cycle 4 (cycle length is equal to [=] 28 days) |
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| Secondary | Percentage of Participants With CR and PR by Cycle 4 | 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. The percentages are rounded off to report the nearest whole numbers. | REP included all participants who received at least 1 dose of study drug and had a Baseline and at least 1 postbaseline disease assessment. Overall number analyzed is the number of participants with data available for analyses. | Posted | Number | percentage of participants | From date of randomization until CR and PR, by Cycle 4 (cycle length=28 days) |
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| Secondary | Percentage of Participants With Overall Response by Cycle 4 | 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. The percentages are rounded off to report the nearest whole numbers. | REP included all participants who received at least 1 dose of study drug and had a Baseline and at least 1 postbaseline disease assessment. Overall number analyzed is the number of participants with data available for analyses. | Posted | Number | percentage of participants | From date of randomization until CR, PR or HI, by Cycle 4 (cycle length=28 days) |
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| Secondary | Percentage of Participants With CR in Low-blast AML by Cycle 4 | 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). The percentages are rounded off to report the nearest whole numbers. | REP included all participants who received at least 1 dose of study drug and had a Baseline and at least 1 postbaseline disease assessment. Data is reported for low blast AML participants which is included as the overall number of participants analyzed. | Posted | Number | percentage of participants | From the date of randomization until CR by Cycle 4 (cycle length=28 days) |
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| Secondary | Duration of Complete Remission (CR) | Duration of CR is first documented CR to the first documentation of PD or relapse from CR (participants with low-blast AML) or relapse after CR or PR (participants with HR MDS/CMML). Disease responses for HR MDS or CMML are based on the Modified IWG Response Criteria for MDS and for low-blast AML on the Revised IWG Response Criteria for AML.CR for HR MDS or CMML≤5% myeloblasts with normal maturation of all cell lines in the bone marrow,≥11 g/dL Hgb,≥100*10^9/L pl,≥1.0*10^9/L neutrophils;0% blasts in peripheral blood.CR for low-blast AML:morphologic leukemia-free state,neutrophils of<1.0*10^9/L;pl of≥100*10^9/L,transfusion independence,no residual evidence of extramedullary leukemia.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). | REP included all participants who received at least 1 dose of study drug and had a Baseline and at least 1 postbaseline disease assessment. Data is reported for the responders with complete remission. | Posted | Median | Full Range | months | From date of randomization until CR (up to approximately 5 years) |
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| Secondary | Duration of Complete Remission (CR) and Partial Remission (PR) | Duration of CR is first documented CR to the first documentation of PD or relapse from CR (participants with low-blast AML). 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. | REP included all participants who received at least 1 dose of study drug and had a Baseline and at least 1 postbaseline disease assessment. Data is reported for the responders with complete CR and PR. | Posted | Median | Full Range | months | From date of randomization until CR or PR (up to approximately 5 years) |
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| Secondary | Duration of Overall Response | Duration of OR: response to first documentation of PD or relapse from CR for low-blast AML or relapse after CR or PR for HR MDS/CMML. Disease responses(HR MDS/CMML): modified IWG criteria for MDS;low-blast AML: revised IWG criteria for AML.Overall response(HR MDS/CMML)=CR,PR/HI,LB AML=CR+ Cri+PR.HR MDS/CMML-CR:≤5%myeloblasts with normal maturation of 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. | REP included all participants who received at least 1 dose of study drug and had a Baseline and at least 1 postbaseline disease assessment. Data is reported for overall responders. | Posted | Median | Full Range | months | From date of randomization until CR, PR or HI (up to approximately 5 years) |
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| Secondary | Duration of Complete Remission (CR) in Low-blast AML | 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). | REP included all participants who received at least 1 dose of study drug and had a Baseline and at least 1 postbaseline disease assessment. Data is reported for responders with low blast AML having complete remission. | Posted | Median | Full Range | months | From date of randomization until CR (up to approximately 5 years) |
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| Secondary | Time to First CR or PR | 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. | REP included all participants who received at least 1 dose of study drug and had a Baseline and at least 1 postbaseline disease assessment. | Posted | Median | 95% Confidence Interval | months | From date of randomization until CR or PR (up to approximately 5 years) |
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| Secondary | Time to Subsequent Therapy | 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 did not be counted as receiving subsequent therapy. | ITT Population was defined as all participants who were randomized. | Posted | Median | 95% Confidence Interval | months | From date of randomization up to approximately 5 years |
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| Secondary | Percentage of Participants With Red Blood Cells (RBCs) and Platelet-transfusion Independence | A participant was defined as RBC or platelet-transfusion independent if he/she received no RBC or platelet transfusions for a period of at least 8 weeks before the first dose of study drug through 30 days after the last dose of any study drug. Rate of transfusion independence was defined as number of participants who became transfusion independent divided by the number of participants who were transfusion dependent at Baseline. | ITT Population included all participants who were randomized. Overall number analyzed are the number of participants from a subset of the ITT Population who were transfusion dependent at Baseline. Number analyzed is the number of participants who were transfusion dependent at Baseline for the specified category. | Posted | Number | percentage of participants | 8 weeks before randomization through 30 days after last dose of any study drug (up to approximately 5 years and 3 months) |
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| Secondary | Percentage of Participants With at Least 1 Inpatient Hospital Admissions Related to HR MDS, CMML or Low-blast AML | Inpatient hospital admission data was 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 occurred 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%. Percentage of participants was calculated as the total number of events divided by the total number of subject-years in each group. | ITT Population included all participants who were randomized. | Posted | Number | 95% Confidence Interval | percentage of participants | From date of randomization until transformation to AML or until initiation of subsequent therapy (up to approximately 5 years) |
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| Secondary | Time to Progressive Disease (PD), Relapse, or Death | 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. | ITT Population was defined as all participants who were randomized. | Posted | Median | Full Range | months | From date of randomization until PD, relapse or death (up to approximately 5 years) |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Number of Participants Reporting One or More Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. A SAE was defined as any untoward medical occurrence that: 1) results in death, 2) is life-threatening, 3) requires inpatient hospitalization or prolongation of existing hospitalization, 4) results in persistent or significant disability/incapacity, 5) leads to a congenital anomaly/birth defect in the offspring of the participant or 6) is an medically important event that satisfies any of the following: a) May require intervention to prevent items 1 through 5 above. b) May expose the participant to danger, even though the event is not immediately life threatening or fatal or does not result in hospitalization. A TEAE was defined as any adverse event occurring after the start of pevonedistat administration of the treatment period. | Safety Population included all enrolled participants who receive at least 1 dose of any study drug azacitidine alone or pevonedistat + azacitidine. | Posted | Count of Participants | Participants | From date of first dose up to 30 days after administration of the last dose of any study drug (up to approximately 5 years) |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Number of Participants in the Safety Analysis Population With Clinically Significant Laboratory Abnormalities Reported as TEAEs | Laboratory assessments included clinical chemistry, hematology, and urinalysis. | Safety Population included all enrolled participants who receive at least 1 dose of any study drug azacitidine alone or pevonedistat + azacitidine. | Posted | Count of Participants | Participants | From date of first dose up to 30 days after administration of the last dose of any study drug (up to approximately 5 years) |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Number of Participants With Change From Baseline Values in Eastern Cooperative Oncology Group (ECOG) Performance Status | 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). | ITT population was defined as all participants who were randomized in the Safety Population. Only categories for which there was at least 1 participant are reported. | Posted | Count of Participants | Participants | From date of first dose up to 30 days after administration of the last dose of any study drug (up to approximately 5 years) |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Number of Participants in the Safety Analysis Population With Clinically Significant Change From Baseline in Electrocardiogram (ECG) Values Reported as TEAEs | ECG assessments included QT, QRS duration, PR interval, ventricular rate, QTcB, QTcF. | Safety Population included all enrolled participants who receive at least 1 dose of any study drug azacitidine alone or pevonedistat + azacitidine. | Posted | Count of Participants | Participants | From date of first dose up to 30 days after administration of the last dose of any study drug (up to approximately 5 years) |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Number of Participants in the Safety Analysis Population With Clinically Significant Change From Baseline Values in Vital Signs Reported as TEAEs | Vital signs assessments included diastolic and systolic blood pressure, heart rate, and body temperature. | Safety Population included all enrolled participants who receive at least 1 dose of any study drug azacitidine alone or pevonedistat + azacitidine. | Posted | Count of Participants | Participants | From date of first dose up to 30 days after administration of the last dose of any study drug (up to approximately 5 years) |
|
From first dose up to 30 days after administration of the last dose of any study drug (up to approximately 5 years)
At each visit the investigator had to document any occurrence of adverse events, abnormal laboratory findings, and vital signs. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Azacitidine 75 mg/m^2 | Azacitidine 75 mg/m^2, infusion, intravenously or subcutaneously, on Day 1 through Day 5, 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). | 50 | 62 | 40 | 62 | 58 | 62 |
| EG001 | Azacitidine 75 mg/m^2 + Pevonedistat 20 mg/m^2 | Azacitidine 75 mg/m^2, infusion, intravenously or subcutaneously, on Day 1 through Day 5, 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). | 47 | 58 | 40 | 58 | 51 | 58 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abdominal pain | Gastrointestinal disorders | MedDRA 23 | Systematic Assessment |
| |
| Abscess limb | Infections and infestations | MedDRA 23 | Systematic Assessment |
| |
| Acute febrile neutrophilic dermatosis | Skin and subcutaneous tissue disorders | MedDRA 23 | Systematic Assessment |
| |
| Acute kidney injury | Renal and urinary disorders | MedDRA 23 | Systematic Assessment |
| |
| Acute myeloid leukaemia | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 23 | Systematic Assessment |
| |
| Anaemia | Blood and lymphatic system disorders | MedDRA 23 | Systematic Assessment |
| |
| Angina unstable | Cardiac disorders | MedDRA 23 | Systematic Assessment |
| |
| Ankle fracture | Injury, poisoning and procedural complications | MedDRA 23 | Systematic Assessment |
| |
| Anuria | Renal and urinary disorders | MedDRA 23 | Systematic Assessment |
| |
| Arthritis | Musculoskeletal and connective tissue disorders | MedDRA 23 | Systematic Assessment |
| |
| Arthritis bacterial | Infections and infestations | MedDRA 23 | Systematic Assessment |
| |
| Arthritis infective | Infections and infestations | MedDRA 23 | Systematic Assessment |
| |
| Arthritis reactive | Musculoskeletal and connective tissue disorders | MedDRA 23 | Systematic Assessment |
| |
| Asthenia | General disorders | MedDRA 23 | Systematic Assessment |
| |
| Atrial fibrillation | Cardiac disorders | MedDRA 23 | Systematic Assessment |
| |
| Atrial flutter | Cardiac disorders | MedDRA 23 | Systematic Assessment |
| |
| Atrioventricular block | Cardiac disorders | MedDRA 23 | Systematic Assessment |
| |
| Atrioventricular block second degree | Cardiac disorders | MedDRA 23 | Systematic Assessment |
| |
| Autoimmune haemolytic anaemia | Blood and lymphatic system disorders | MedDRA 23 | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 23 | Systematic Assessment |
| |
| Bacteraemia | Infections and infestations | MedDRA 23 | Systematic Assessment |
| |
| Bacterial sepsis | Infections and infestations | MedDRA 23 | Systematic Assessment |
| |
| Benign prostatic hyperplasia | Reproductive system and breast disorders | MedDRA 23 | Systematic Assessment |
| |
| Bronchitis | Infections and infestations | MedDRA 23 | Systematic Assessment |
| |
| Bronchopulmonary aspergillosis | Infections and infestations | MedDRA 23 | Systematic Assessment |
| |
| Cardiac failure | Cardiac disorders | MedDRA 23 | Systematic Assessment |
| |
| Cardiac failure acute | Cardiac disorders | MedDRA 23 | Systematic Assessment |
| |
| Cardio-respiratory arrest | Cardiac disorders | MedDRA 23 | Systematic Assessment |
| |
| Cauda equina syndrome | Nervous system disorders | MedDRA 23 | Systematic Assessment |
| |
| Cellulitis | Infections and infestations | MedDRA 23 | Systematic Assessment |
| |
| Cerebral ischaemia | Nervous system disorders | MedDRA 23 | Systematic Assessment |
| |
| Cerebrovascular accident | Nervous system disorders | MedDRA 23 | Systematic Assessment |
| |
| Cholecystitis | Hepatobiliary disorders | MedDRA 23 | Systematic Assessment |
| |
| Chondrocalcinosis pyrophosphate | Musculoskeletal and connective tissue disorders | MedDRA 23 | Systematic Assessment |
| |
| Chronic kidney disease | Renal and urinary disorders | MedDRA 23 | Systematic Assessment |
| |
| Congestive cardiomyopathy | Cardiac disorders | MedDRA 23 | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA 23 | Systematic Assessment |
| |
| Coronavirus infection | Infections and infestations | MedDRA 23 | Systematic Assessment |
| |
| Death | General disorders | MedDRA 23 | Systematic Assessment |
| |
| Deep vein thrombosis | Vascular disorders | MedDRA 23 | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA 23 | Systematic Assessment |
| |
| Drug hypersensitivity | Immune system disorders | MedDRA 23 | Systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 23 | Systematic Assessment |
| |
| Ear pain | Ear and labyrinth disorders | MedDRA 23 | Systematic Assessment |
| |
| Embolic stroke | Nervous system disorders | MedDRA 23 | Systematic Assessment |
| |
| Endocarditis | Infections and infestations | MedDRA 23 | Systematic Assessment |
| |
| Failure to thrive | Metabolism and nutrition disorders | MedDRA 23 | Systematic Assessment |
| |
| Fall | Injury, poisoning and procedural complications | MedDRA 23 | Systematic Assessment |
| |
| Febrile neutropenia | Blood and lymphatic system disorders | MedDRA 23 | Systematic Assessment |
| |
| Gastric haemorrhage | Gastrointestinal disorders | MedDRA 23 | Systematic Assessment |
| |
| Gastritis erosive | Gastrointestinal disorders | MedDRA 23 | Systematic Assessment |
| |
| Gastrointestinal necrosis | Gastrointestinal disorders | MedDRA 23 | Systematic Assessment |
| |
| Gastrointestinal ulcer perforation | Gastrointestinal disorders | MedDRA 23 | Systematic Assessment |
| |
| Haematoma | Vascular disorders | MedDRA 23 | Systematic Assessment |
| |
| Haematuria | Renal and urinary disorders | MedDRA 23 | Systematic Assessment |
| |
| Haemorrhage intracranial | Nervous system disorders | MedDRA 23 | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA 23 | Systematic Assessment |
| |
| Hepatic lesion | Hepatobiliary disorders | MedDRA 23 | Systematic Assessment |
| |
| Hip fracture | Injury, poisoning and procedural complications | MedDRA 23 | Systematic Assessment |
| |
| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA 23 | Systematic Assessment |
| |
| Hypoxia | Respiratory, thoracic and mediastinal disorders | MedDRA 23 | Systematic Assessment |
| |
| Influenza | Infections and infestations | MedDRA 23 | Systematic Assessment |
| |
| Inguinal hernia | Gastrointestinal disorders | MedDRA 23 | Systematic Assessment |
| |
| Ischaemic gastritis | Gastrointestinal disorders | MedDRA 23 | Systematic Assessment |
| |
| Left ventricular failure | Cardiac disorders | MedDRA 23 | Systematic Assessment |
| |
| Leukopenia | Blood and lymphatic system disorders | MedDRA 23 | Systematic Assessment |
| |
| Localised infection | Infections and infestations | MedDRA 23 | Systematic Assessment |
| |
| Lower respiratory tract infection | Infections and infestations | MedDRA 23 | Systematic Assessment |
| |
| Lung carcinoma cell type unspecified recurrent | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 23 | Systematic Assessment |
| |
| Lung infiltration | Respiratory, thoracic and mediastinal disorders | MedDRA 23 | Systematic Assessment |
| |
| Malaise | General disorders | MedDRA 23 | Systematic Assessment |
| |
| Melaena | Gastrointestinal disorders | MedDRA 23 | Systematic Assessment |
| |
| Mental status changes | Psychiatric disorders | MedDRA 23 | Systematic Assessment |
| |
| Multiple organ dysfunction syndrome | General disorders | MedDRA 23 | Systematic Assessment |
| |
| Myelodysplastic syndrome | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 23 | Systematic Assessment |
| |
| Myelodysplastic syndrome transformation | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 23 | Systematic Assessment |
| |
| Myocardial infarction | Cardiac disorders | MedDRA 23 | Systematic Assessment |
| |
| Neutropenia | Blood and lymphatic system disorders | MedDRA 23 | Systematic Assessment |
| |
| Non-cardiac chest pain | General disorders | MedDRA 23 | Systematic Assessment |
| |
| Oral viral infection | Infections and infestations | MedDRA 23 | Systematic Assessment |
| |
| Osteonecrosis | Musculoskeletal and connective tissue disorders | MedDRA 23 | Systematic Assessment |
| |
| Pain in jaw | Musculoskeletal and connective tissue disorders | MedDRA 23 | Systematic Assessment |
| |
| Parophthalmia | Eye disorders | MedDRA 23 | Systematic Assessment |
| |
| Peripheral venous disease | Vascular disorders | MedDRA 23 | Systematic Assessment |
| |
| Pneumocystis jirovecii pneumonia | Infections and infestations | MedDRA 23 | Systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA 23 | Systematic Assessment |
| |
| Post procedural hypotension | Injury, poisoning and procedural complications | MedDRA 23 | Systematic Assessment |
| |
| Proctitis | Gastrointestinal disorders | MedDRA 23 | Systematic Assessment |
| |
| Prostate cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 23 | Systematic Assessment |
| |
| Pseudomonas infection | Infections and infestations | MedDRA 23 | Systematic Assessment |
| |
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | MedDRA 23 | Systematic Assessment |
| |
| Pulmonary sepsis | Infections and infestations | MedDRA 23 | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA 23 | Systematic Assessment |
| |
| Rectal haemorrhage | Gastrointestinal disorders | MedDRA 23 | Systematic Assessment |
| |
| Renal colic | Renal and urinary disorders | MedDRA 23 | Systematic Assessment |
| |
| Renal failure | Renal and urinary disorders | MedDRA 23 | Systematic Assessment |
| |
| Respiratory distress | Respiratory, thoracic and mediastinal disorders | MedDRA 23 | Systematic Assessment |
| |
| Respiratory failure | Respiratory, thoracic and mediastinal disorders | MedDRA 23 | Systematic Assessment |
| |
| Respiratory syncytial virus bronchiolitis | Infections and infestations | MedDRA 23 | Systematic Assessment |
| |
| Respiratory tract infection | Infections and infestations | MedDRA 23 | Systematic Assessment |
| |
| Rotator cuff syndrome | Musculoskeletal and connective tissue disorders | MedDRA 23 | Systematic Assessment |
| |
| SARS-CoV-2 test positive | Investigations | MedDRA 23 | Systematic Assessment |
| |
| Sepsis | Infections and infestations | MedDRA 23 | Systematic Assessment |
| |
| Sinusitis | Infections and infestations | MedDRA 23 | Systematic Assessment |
| |
| Soft tissue infection | Infections and infestations | MedDRA 23 | Systematic Assessment |
| |
| Spinal compression fracture | Injury, poisoning and procedural complications | MedDRA 23 | Systematic Assessment |
| |
| Squamous cell carcinoma of skin | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 23 | Systematic Assessment |
| |
| Staphylococcal bacteraemia | Infections and infestations | MedDRA 23 | Systematic Assessment |
| |
| Supraventricular tachycardia | Cardiac disorders | MedDRA 23 | Systematic Assessment |
| |
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA 23 | Systematic Assessment |
| |
| Thrombophlebitis superficial | Vascular disorders | MedDRA 23 | Systematic Assessment |
| |
| Upper respiratory tract infection | Infections and infestations | MedDRA 23 | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA 23 | Systematic Assessment |
| |
| Urinary tract infection enterococcal | Infections and infestations | MedDRA 23 | Systematic Assessment |
| |
| Urinary tract obstruction | Renal and urinary disorders | MedDRA 23 | Systematic Assessment |
| |
| Viral infection | Infections and infestations | MedDRA 23 | Systematic Assessment |
| |
| Wound infection | Infections and infestations | MedDRA 23 | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abdominal pain | Gastrointestinal disorders | MedDRA 23 | Systematic Assessment |
| |
| Acute kidney injury | Renal and urinary disorders | MedDRA 23 | Systematic Assessment |
| |
| Alanine aminotransferase increased | Investigations | MedDRA 23 | Systematic Assessment |
| |
| Anaemia | Blood and lymphatic system disorders | MedDRA 23 | Systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 23 | Systematic Assessment |
| |
| Aspartate aminotransferase increased | Investigations | MedDRA 23 | Systematic Assessment |
| |
| Asthenia | General disorders | MedDRA 23 | Systematic Assessment |
| |
| Atrial fibrillation | Cardiac disorders | MedDRA 23 | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 23 | Systematic Assessment |
| |
| Blood alkaline phosphatase increased | Investigations | MedDRA 23 | Systematic Assessment |
| |
| Blood bilirubin increased | Investigations | MedDRA 23 | Systematic Assessment |
| |
| Blood creatinine increased | Investigations | MedDRA 23 | Systematic Assessment |
| |
| Bronchitis | Infections and infestations | MedDRA 23 | Systematic Assessment |
| |
| Chills | General disorders | MedDRA 23 | Systematic Assessment |
| |
| Conjunctival haemorrhage | Eye disorders | MedDRA 23 | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA 23 | Systematic Assessment |
| |
| Contusion | Injury, poisoning and procedural complications | MedDRA 23 | Systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 23 | Systematic Assessment |
| |
| Decreased appetite | Metabolism and nutrition disorders | MedDRA 23 | Systematic Assessment |
| |
| Dehydration | Metabolism and nutrition disorders | MedDRA 23 | Systematic Assessment |
| |
| Depression | Psychiatric disorders | MedDRA 23 | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA 23 | Systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA 23 | Systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 23 | Systematic Assessment |
| |
| Dyspnoea exertional | Respiratory, thoracic and mediastinal disorders | MedDRA 23 | Systematic Assessment |
| |
| Dysuria | Renal and urinary disorders | MedDRA 23 | Systematic Assessment |
| |
| Ear pain | Ear and labyrinth disorders | MedDRA 23 | Systematic Assessment |
| |
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA 23 | Systematic Assessment |
| |
| Erythema | Skin and subcutaneous tissue disorders | MedDRA 23 | Systematic Assessment |
| |
| Fall | Injury, poisoning and procedural complications | MedDRA 23 | Systematic Assessment |
| |
| Fatigue | General disorders | MedDRA 23 | Systematic Assessment |
| |
| Febrile neutropenia | Blood and lymphatic system disorders | MedDRA 23 | Systematic Assessment |
| |
| Haematoma | Vascular disorders | MedDRA 23 | Systematic Assessment |
| |
| Haematuria | Renal and urinary disorders | MedDRA 23 | Systematic Assessment |
| |
| Haemorrhoids | Gastrointestinal disorders | MedDRA 23 | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA 23 | Systematic Assessment |
| |
| Hyperkalaemia | Metabolism and nutrition disorders | MedDRA 23 | Systematic Assessment |
| |
| Hypertension | Vascular disorders | MedDRA 23 | Systematic Assessment |
| |
| Hypoalbuminaemia | Metabolism and nutrition disorders | MedDRA 23 | Systematic Assessment |
| |
| Hypocalcaemia | Metabolism and nutrition disorders | MedDRA 23 | Systematic Assessment |
| |
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA 23 | Systematic Assessment |
| |
| Hypomagnesaemia | Metabolism and nutrition disorders | MedDRA 23 | Systematic Assessment |
| |
| Hyponatraemia | Metabolism and nutrition disorders | MedDRA 23 | Systematic Assessment |
| |
| Hypophosphataemia | Metabolism and nutrition disorders | MedDRA 23 | Systematic Assessment |
| |
| Hypotension | Vascular disorders | MedDRA 23 | Systematic Assessment |
| |
| Injection site pain | General disorders | MedDRA 23 | Systematic Assessment |
| |
| Injection site reaction | General disorders | MedDRA 23 | Systematic Assessment |
| |
| Insomnia | Psychiatric disorders | MedDRA 23 | Systematic Assessment |
| |
| Malaise | General disorders | MedDRA 23 | Systematic Assessment |
| |
| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA 23 | Systematic Assessment |
| |
| Muscular weakness | Musculoskeletal and connective tissue disorders | MedDRA 23 | Systematic Assessment |
| |
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA 23 | Systematic Assessment |
| |
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA 23 | Systematic Assessment |
| |
| Nasal congestion | Respiratory, thoracic and mediastinal disorders | MedDRA 23 | Systematic Assessment |
| |
| Nasopharyngitis | Infections and infestations | MedDRA 23 | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA 23 | Systematic Assessment |
| |
| Neutropenia | Blood and lymphatic system disorders | MedDRA 23 | Systematic Assessment |
| |
| Neutrophil count decreased | Investigations | MedDRA 23 | Systematic Assessment |
| |
| Non-cardiac chest pain | General disorders | MedDRA 23 | Systematic Assessment |
| |
| Oedema peripheral | General disorders | MedDRA 23 | Systematic Assessment |
| |
| Oral candidiasis | Infections and infestations | MedDRA 23 | Systematic Assessment |
| |
| Oral herpes | Infections and infestations | MedDRA 23 | Systematic Assessment |
| |
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA 23 | Systematic Assessment |
| |
| Pain | General disorders | MedDRA 23 | Systematic Assessment |
| |
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA 23 | Systematic Assessment |
| |
| Pallor | Vascular disorders | MedDRA 23 | Systematic Assessment |
| |
| Peripheral swelling | General disorders | MedDRA 23 | Systematic Assessment |
| |
| Petechiae | Skin and subcutaneous tissue disorders | MedDRA 23 | Systematic Assessment |
| |
| Platelet count decreased | Investigations | MedDRA 23 | Systematic Assessment |
| |
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | MedDRA 23 | Systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA 23 | Systematic Assessment |
| |
| Productive cough | Respiratory, thoracic and mediastinal disorders | MedDRA 23 | Systematic Assessment |
| |
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA 23 | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA 23 | Systematic Assessment |
| |
| Rash maculo-papular | Skin and subcutaneous tissue disorders | MedDRA 23 | Systematic Assessment |
| |
| Respiratory tract infection | Infections and infestations | MedDRA 23 | Systematic Assessment |
| |
| Somnolence | Nervous system disorders | MedDRA 23 | Systematic Assessment |
| |
| Stomatitis | Gastrointestinal disorders | MedDRA 23 | Systematic Assessment |
| |
| Tachycardia | Cardiac disorders | MedDRA 23 | Systematic Assessment |
| |
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA 23 | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA 23 | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA 23 | Systematic Assessment |
| |
| Weight decreased | Investigations | MedDRA 23 | Systematic Assessment |
| |
| White blood cell count decreased | Investigations | MedDRA 23 | Systematic Assessment |
|
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.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Study Director | Takeda | +1-877-825-3327 | TrialDisclosures@takeda.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Aug 6, 2019 | Aug 31, 2020 | SAP_001.pdf |
| ID | Term |
|---|---|
| D009190 | Myelodysplastic Syndromes |
| D015477 | Leukemia, Myelomonocytic, Chronic |
| D015470 | Leukemia, Myeloid, Acute |
| ID | Term |
|---|---|
| D001855 | Bone Marrow Diseases |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D007951 | Leukemia, Myeloid |
| D007938 | Leukemia |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D054437 | Myelodysplastic-Myeloproliferative Diseases |
| D002908 | Chronic Disease |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
Not provided
Not provided
| ID | Term |
|---|---|
| D001374 | Azacitidine |
| C539933 | pevonedistat |
| 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 |
Not provided
Not provided
| Male |
|
| Not Hispanic or Latino |
|
| Unknown or Not Reported |
|
| Asian |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
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| Unknown or Not Reported |
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| United States |
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| Belgium |
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| Bulgaria |
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| Czech Republic |
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| Germany |
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| Spain |
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| France |
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| Ireland |
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| Israel |
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| Italy |
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Azacitidine 75 mg/m^2, infusion, intravenously or subcutaneously, on Day 1 through Day 5, 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). |
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| Participants |
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| Participants |
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| OG001 |
| Azacitidine 75 mg/m^2 + Pevonedistat 20 mg/m^2 |
Azacitidine 75 mg/m^2, infusion, intravenously or subcutaneously, on Day 1 through Day 5, 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). |
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| OG001 | Azacitidine 75 mg/m^2 + Pevonedistat 20 mg/m^2 | Azacitidine 75 mg/m^2, infusion, intravenously or subcutaneously, on Day 1 through Day 5, 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). |
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| OG001 | Azacitidine 75 mg/m^2 + Pevonedistat 20 mg/m^2 | Azacitidine 75 mg/m^2, infusion, intravenously or subcutaneously, on Day 1 through Day 5, 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). |
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Azacitidine 75 mg/m^2, infusion, intravenously or subcutaneously, on Day 1 through Day 5, 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). |
|
|
|
| OG001 | Azacitidine 75 mg/m^2 + Pevonedistat 20 mg/m^2 | Azacitidine 75 mg/m^2, infusion, intravenously or subcutaneously, on Day 1 through Day 5, 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). |
|
|
|
| OG001 | Azacitidine 75 mg/m^2 + Pevonedistat 20 mg/m^2 | Azacitidine 75 mg/m^2, infusion, intravenously or subcutaneously, on Day 1 through Day 5, 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). |
|
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|
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|
Azacitidine 75 mg/m^2, infusion, intravenously or subcutaneously, on Day 1 through Day 5, 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). |
|
|
|
| OG001 | Azacitidine 75 mg/m^2 + Pevonedistat 20 mg/m^2 | Azacitidine 75 mg/m^2, infusion, intravenously or subcutaneously, on Day 1 through Day 5, 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). |
|
|
|
| OG001 | Azacitidine 75 mg/m^2 + Pevonedistat 20 mg/m^2 | Azacitidine 75 mg/m^2, infusion, intravenously or subcutaneously, on Day 1 through Day 5, 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). |
|
|
|
|
|
|
| Azacitidine 75 mg/m^2 + Pevonedistat 20 mg/m^2 |
Azacitidine 75 mg/m^2, infusion, intravenously or subcutaneously, on Day 1 through Day 5, 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). |
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| Units | Counts |
|---|---|
| Participants |
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|
|
|
Azacitidine 75 mg/m^2, infusion, intravenously or subcutaneously, on Day 1 through Day 5, 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). |
|
|
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| OG001 | Azacitidine 75 mg/m^2 + Pevonedistat 20 mg/m^2 | 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). |
|
|
| Units | Counts |
|---|---|
| Participants |
|
|
| OG001 | Azacitidine 75 mg/m^2 + Pevonedistat 20 mg/m^2 | 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). |
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| Units | Counts |
|---|---|
| Participants |
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| Units | Counts |
|---|---|
| Participants |
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