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| ID | Type | Description | Link |
|---|---|---|---|
| U1111-1220-1396 | Other Identifier | WHO | |
| 2018-004049-17 | EudraCT Number |
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Pevonedistat is a medicine to treat people with blood cancers or solid tumors.
The main aim of the study is to learn about the levels of pevonedistat in the blood of participants with blood cancers or solid tumors, who also have severe kidney problems or mild to moderate liver problems. The information from this study will be used to work out the best dose of pevonedistat to give people with these conditions in future studies. At the first visit, the study doctor will check who can take part in the study.
This study is in 2 parts: A and B.
Part A Participants will be placed into 1 of 4 treatment groups depending on how severe their kidney and liver problems are. All participants will receive 1 dose of pevonedistat as a slow injection in their vein (infusion). Then, the study doctors will check the levels of pevonedistat in the blood of the participants for 3 days after the infusion. They will also check if the participants have any side effects from pevonedistat.
Participants will be asked to continue to Part B. Those who don't want to continue will visit the clinic 30 days later for a final check-up.
Part B Participants who agree to participate into Part B will receive an infusion of pevonedistat on specific days during a 21-day or 28-day cycle. The cycle time will depend on what type of cancer the participants have. Participants will also be treated with standard of care medicines for their kidney and liver problems during this time. In the first cycle, the study doctors will also check the levels of pevonedistat in the blood and urine of participants for 3 days after the infusion. Participants will continue with cycles of treatment together with standard of care medicines until their condition gets worse or they have too many side effects from the treatment.
When treatment has finished, participants will visit the clinic 10 days later for a final check-up.
The drug being tested in this study is called pevonedistat. The study will characterize the PK of pevonedistat, assess the safety, and determine the dose of pevonedistat, in combination with azacitidine, docetaxel OR paclitaxel plus carboplatin in participants with higher-risk myelodysplastic syndromes (HRMDS), myelodysplastic syndromes (MDS), chronic myelomonocytic leukemia (CMML), acute myelogenous leukemia (AML), or advanced solid tumors who also have severe renal impairment or mild or moderate hepatic impairment.
The study will enroll approximately 42 participants. Participants with solid tumors or hematologic malignancies will be assigned to one of the four treatment groups on the basis of their renal and hepatic function:
The study will be conducted in 2 parts: Part A and Part B. Part A will include single dose administration of pevonedistat. Eligible participants from Part A who will opt to continue treatment in Part B will be treated with pevonedistat in combination with standard of care (SOC) agents (azacitidine, docetaxel OR paclitaxel plus carboplatin) in Part B.
Intrapatient dose escalation of pevonedistat and SOC agents will be based on the safety data from Cycle 1 of Part B as mentioned below:
This multi-center trial will be conducted in the United States and Spain. The overall time to participate in this study is approximately 3.5 years. Participants will attend end of the study visit 30 days after the last dose of study drug or before the start of subsequent therapy, if that occurs sooner for safety follow up.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Control Arm | Experimental | Pevonedistat 20 milligram per square meter (mg/m^2), infusion, intravenously, once, on Day 1 of Part A in participants with hematologic malignancies, followed by a washout period of approximately 4 to 7 days, further followed by azacitidine 75 mg/m^2, injection, subcutaneously in Cycle 1 or subcutaneously or intravenously in Cycle 2 and subsequent cycles, once on Day 1 through Day 7 or Day 1 through Day 5, and on Days 8 and 9 in combination with pevonedistat 20 mg/m^2, infusion, intravenously, once, on Days 1, 3, and 5 in each 28-day treatment cycle in participants with hematologic malignancies until symptomatic deterioration or PD, discontinuation for any reason, study stopped by the sponsor, or up to 12 cycles. |
|
| Renal Arm | Experimental | Pevonedistat 20 mg/m^2, infusion, intravenously, once, on Day 1 of Part A in participants with hematologic malignancies, followed by a washout period of approximately 4 to 7 days, further followed by azacitidine 75 mg/m^2, injection, subcutaneously in Cycle 1 or subcutaneously or intravenously in Cycle 2 and subsequent cycles, once on Day 1 through Day 7 or Day 1 through Day 5, and on Days 8-9 in combination with a starting dose of pevonedistat 10 mg/m^2 to a maximum dose of pevonedistat 15 mg/m^2, infusion, intravenously, once, on Days 1, 3, and 5 in each 28-day treatment cycle in participants with hematologic malignancies until symptomatic deterioration or PD, discontinuation for any reason, study stopped by the sponsor, or up to 12 cycles. |
|
| Mild Hepatic Arm | Experimental | Pevonedistat 20 mg/m^2, infusion, intravenously, once, on Day 1 of Part A in participants with hematologic malignancies, followed by a washout period of approximately 4 to 7 days, further followed by azacitidine 75 mg/m^2, injection, subcutaneously in Cycle 1 or subcutaneously or intravenously in Cycle 2 and subsequent cycles, once on Day 1 through Day 7 or Day 1 through Day 5, and on Days 8 and 9 in combination with a starting dose of pevonedistat 10 mg/m^2 to a maximum dose of pevonedistat 20 mg/m^2, infusion, intravenously, once, on Days 1, 3, and 5 in each 28-day treatment cycle in participants with hematologic malignancies until symptomatic deterioration or PD, discontinuation for any reason, study stopped by the sponsor, or up to 12 cycles. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Azacitidine | Drug | Azacitidine subcutaneous or intravenous injection. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Part A, AUC∞: Area Under the Plasma Concentration-time Curve From Time Zero to Infinity for Pevonedistat Following a Single Dose | Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose | |
| Part A, AUClast: Area Under the Plasma Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration for Pevonedistat Following a Single Dose | Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose | |
| Part A, Cmax: Maximum Observed Plasma Concentration for Pevonedistat Following a Single Dose | Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose |
| Measure | Description | Time Frame |
|---|---|---|
| Parts A and B, t1/2z: Terminal Disposition Phase Half-life for Pevonedistat Following Single and Multiple Dose | Part A: Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose; Part B: Cycle 1 Day 3 pre-dose and at multiple time points (up to 48 hours) post-dose (Cycle length= 28 days) | |
| Part B: Cmax: Maximum Observed Plasma Concentration for Pevonedistat Following Multiple Dose |
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Inclusion Criteria:
All participants:
Has expected survival of at least 3 months from the date of enrollment in the study.
Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.
Has recovered (that is, Grade <=1 toxicity) from the reversible effects of prior anticancer therapy.
Prothrombin time (PT) and activated partial thromboplastin time (aPTT) <=1.5 * upper limit of the normal range (ULN) at screening or within 7 days before the first dose of study drug.
Suitable venous access for the study-required blood sampling (that is, PK sampling).
For hematologic malignancies:
Previously untreated hematologic malignancies not suitable for induction therapy.
Morphologically confirmed diagnosis of MDS or nonproliferative CMML (that is, with white blood cell [WBC] <13,000 /mcL) at the study entry, based on one of the following:
French-American-British (FAB) Classifications:
OR
World Health Organization (WHO) Classifications:
With MDS or CMML and must also have one of the following Prognostic Risk Categories, based on the Revised International Prognostic Scoring System (IPSS-R):
With WHO-defined AML at study entry, including leukemia secondary to prior chemotherapy or resulting from an antecedent hematologic disorder, have failed to achieve CR or have relapsed after prior therapy and are not candidates for potentially curative treatment.
With relapsed or refractory MDS, have previously been treated with an hypomethylating agent.
Laboratory value requirements per study arms are:
For advanced solid tumors:
Have a histologically or cytologically confirmed metastatic or locally advanced solid tumor that is appropriate for treatment with pevonedistat in combination with either docetaxel or carboplatin plus paclitaxel in Part B of this study, or have progressed despite standard therapy, or whom conventional therapy is not considered effective.
Computerized tomography (CT) scan or magnetic resonance imaging (MRI) of the chest, abdomen, and pelvis within 28 days of the first dose of the study drug.
Laboratory value requirements per study arms are:
Exclusion Criteria:
All participants:-
With end-stage renal disease requiring hemodialysis.
Has Gilbert syndrome.
Has active uncontrolled infection or severe infectious disease, such as severe pneumonia, meningitis, or septicemia. Prophylactic treatment with antibiotics is allowed.
Has life-threatening illness unrelated to cancer.
Known human immunodeficiency virus (HIV) seropositive.
Treatment with strong cytochrome P450 (CYP)3A inducers within 14 days before the first dose of pevonedistat.
Has left ventricular ejection fraction (LVEF) <50% within 6 months prior to study enrollment. If a result within this time frame is unavailable, LVEF must be determined by echocardiography or multigated acquisition scan at screening.
Has severe uncontrolled ventricular arrhythmias or torsade de pointes; electrocardiographic evidence of acute ischemia or active conduction system abnormalities; or clinically significant arrhythmia (as an example, well-controlled atrial fibrillation would not be an exclusion whereas uncontrolled atrial fibrillation would be an exclusion).
Has severe symptomatic pulmonary hypertension requiring pharmacologic therapy or participants with chronic respiratory disease that requires continuous oxygen.
For hematologic malignancies:
Has acute promyelocytic leukemia as diagnosed by morphologic examination of bone marrow, by fluorescent in situ hybridization or cytogenetics of peripheral blood or bone marrow, or by other accepted analysis.
With AML with a WBC count >=50,000/mcL. Participants who are cytoreduced with leukapheresis or with hydroxyurea may be enrolled if they otherwise meet the eligibility criteria.
With either clinical evidence of or history of central nervous system (CNS) involvement by AML.
With hematologic malignancies, PT or aPTT >1.5 * ULN or active uncontrolled coagulopathy or bleeding disorder. Participants therapeutically anticoagulated with warfarin, direct thrombin inhibitors, direct factor Xa inhibitors, or heparin are excluded from enrollment.
For advanced solid tumors:
Has prior treatment with radiation therapy involving >=25% of the hematopoietically active bone marrow.
Has CNS metastasis, except for participants who have received prior treatment (radiation or resection) and have stable CNS disease (example: stable MRI, no steroid requirement).
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| Name | Affiliation | Role |
|---|---|---|
| Medical Director | Takeda | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Icahn School of Medicine at Mount Sinai | New York | New York | 10029 | United States | ||
| University of North Carolina at Chapel Hill |
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| Label | URL |
|---|---|
| To obtain more information on the study, click here/on this link | View source |
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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 with myelodysplastic syndromes (MDS), and acute myelogenous leukemia (AML) who also had severe renal impairment or mild hepatic impairment were enrolled in this study to receive single dose of pevonedistat in Part A followed by a wash out period and pevonedistat in combination with standard of care agent in Part B. No participants with chronic myelomonocytic leukemia (CMML) and solid tumors were enrolled in this study.
Participants took part in the study at 5 investigative sites in United States and Spain from 10 July 2019 to 19 April 2022.
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| ID | Title | Description |
|---|---|---|
| FG000 | Control Arm | Pevonedistat 20 mg/m^2, infusion, intravenously (IV), once, on Day 1 of Part A in participants with hematologic malignancies, followed by a washout period of approximately 4 to 7 days. Following Part A participants received azacitidine 75 mg/m^2, injection, subcutaneously (SC) in Cycle 1 or SC or IV in Cycle 2 and subsequent cycles, once on Day 1 through Day 7 or Day 1 through Day 5, and on Days 8 and 9 in combination with pevonedistat 20 mg/m^2, infusion, IV, once, on Days 1, 3, and 5 in each 28-day treatment cycle in participants with hematologic malignancies in Part B until symptomatic deterioration or PD, discontinuation for any reason, study stopped by the sponsor, or up to 12 cycles. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Part A: Day 1 to Day 4 |
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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 | Jun 1, 2021 | Apr 18, 2023 |
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| Pevonedistat | Drug | Pevonedistat intravenous infusion. |
|
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| Cycle 1 Day 3 pre-dose and at multiple time points (up to 48 hours) post-dose (Cycle length= 28 days) |
| Parts A, fu: Fraction of Unbound Drug in Plasma for Pevonedistat | Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose |
| Part B, Cmax: Maximum Observed Plasma Concentration for Azacitidine Following Multiple Dose | Cycle 1 Day 3 pre-dose and at multiple time points (up to 7 hours) post-dose (Cycle length= 28 days) |
| Part B, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Azacitidine Following Multiple Dose | Cycle 1 Day 3 pre-dose and at multiple time points (up to 7 hours) post-dose (Cycle length= 28 days) |
| Part B, t1/2z: Terminal Disposition Phase Half-life for Azacitidine Following Multiple-dose | Cycle 1 Day 3 pre-dose and at multiple time points (up to 7 hours) post-dose (Cycle length= 28 days) |
| Part B, AUCÏ„: Area Under the Concentration-time Curve From Time Zero to the End of the Dosing Interval for Pevonedistat Following Multiple Dose | Cycle 1 Day 3 pre-dose and at multiple time points (up to 48 hours) post-dose (Cycle length= 28 days) |
| Part B, AUCÏ„: Area Under the Concentration-time Curve From Time Zero to the End of the Dosing Interval for Azacitidine Following Multiple Dose | Cycle 1 Day 3 pre-dose and at multiple time points (up to 7 hours) post-dose (Cycle length= 28 days) |
| Parts A and B, CL: Total Clearance for Pevonedistat | Part A: Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose; Part B: Cycle 1 Day 3 pre-dose and at multiple time points (up to 48 hours) post-dose (Cycle length is 28 Days) |
| Part B, CL/F: Apparent Clearance for Azacitidine | Cycle 1 Day 3 pre-dose and at multiple time points (up to 8 hours) post-dose (Cycle length= 28 days) |
| Part B, CLR: Renal Clearance for Pevonedistat | Cycle 1 Day 3 pre-dose and at multiple time points (up to 8 hours) post-dose (Cycle length= 28 days) |
| Part B, CLR: Renal Clearance for Azacitidine | Cycle 1 Day 3 pre-dose and at multiple time points (up to 8 hours) post-dose (Cycle length= 28 days) |
| Parts A and B, Vss: Volume of Distribution at Steady-state of Pevonedistat | Part A: Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose; Part B: Cycle 1 Day 3 pre-dose and at multiple time points (up to 48 hours) post-dose (Cycle length= 28 days) |
| Part B, Vz/F: Apparent Volume of Distribution of Azacitidine | Cycle 1 Day 3 pre-dose and at multiple time points (up to 8 hours) post-dose (Cycle length= 28 days) |
| Part B: Percentage of AML Participants With Complete Response/ Remission (CR) or CR With Incomplete Blood Count Recovery (CRi) or Partial Response (PR) | Disease response in AML are based on international working group (IWG) for diagnosis, standardization of response criteria, treatment outcomes, and reporting standards for therapeutic trials in AML. For AML participants, all CR includes both CR and CRi. CR: morphologic leukemia-free state with absolute neutrophil count (ANC) of greater than (>) 1000 per microliter (/mcL) and platelets of greater than or equal to (>=) 100,000/mcL, and no residual evidence of extramedullary leukemia. CRi: After chemotherapy, some participants fulfill all criteria for CR except for residual neutropenia (less than [<] 1000/mcL) or thrombocytopenia (<100,000/mcL). PR: requires all hematologic values for a CR but with a decrease of at least 50 percent (%) in the percentage of blasts to 5% to 25% in the bone marrow aspirate. A value of less than or equal to (<=) 5% blasts may also be considered a PR if Auer rods are present. | Cycle 2 Day 22, Cycles 5, 8, and 11 (between Days 15 and 28), and every 6 cycles (up to 2 years 9 months) (Cycle length= 28 days) |
| Part B: Percentage of MDS and CMML Participants With CR, PR or Hematologic Improvement (HI) | Disease response in MDS and CMML was based on best overall response (CR+PR+HI) as determined by investigator using revised IWG response criteria for MDS and CMML. CR: morphologic leukemia-free state with absolute neutrophil count (ANC) of greater than (>) 1000 per microliter (/mcL) and platelets of greater than or equal to (>=) 100,000/mcL, and no residual evidence of extramedullary leukemia. PR: requires all hematologic values for a CR but with a decrease of at least 50 percent (%) in the percentage of blasts to 5% to 25% in the bone marrow aspirate. A value of less than or equal to (<=) 5% blasts may also be considered a PR if Auer rods are present. HI: erythropoietic (HI-E): Hemoglobin increase of ≥ 1.5 g/dL untransfused, for red blood cells (RBC) transfusions performed for hemoglobin ≤ 9.0: reduction in RBC units transfused in 8 weeks by ≥ 4 units compared to the number of units transfused in the 8 weeks prior to treatment. No participants with CMML were enrolled in this study. | Cycle 2 Day 22, Cycles 5, 8, and 11 (between Days 15 and 28), and every 6 cycles (up to 2 years 9 months) (Cycle length= 28 days) |
| Part B: Percentage of HR MDS and AML Participants With Overall Response | Overall Response Rate is defined as CR+CRi+PR+HI. CR:≤5% myeloblasts with normal maturation of all bone marrow(BM)cell lines,≥11g/dL Hgb,≥100*10^9/L pl,≥1.0*10^9/L neutrophils,0% blasts in peripheral blood;PR:all CR criteria met except BM blasts ≥50% decrease over pretreatment but still >5%;HI:Hgb increase(inc) ≥1.5g/dL if baseline(BL)<11 g/dL;pl inc≥30*10^9/L if BL>20*10^9/L or inc from <20*10^9/L to >20*10^9/L and by 100%;neutrophil inc by 100%;absolute inc of >0.5*10^9/L if BL<100*10^9/L.For AML-CR:morphologic leukemia-free state >1.0*10^9 neutrophils,≥100*10^9/L pl,transfusion independence,no residual evidence of extramedullary leukemia;CR with incomplete blood count recovery:fulfill CR criteria except residual neutropenia (<1000/μL) or thrombocytopenia (<100,000/μL);PR:all CR hematological values but ≥50% decrease in BM aspirate. | Cycle 2 Day 22, Cycles 5, 8, and 11 (between Days 15 and 28), and every 6 cycles (up to 2 years 9 months) (Cycle length= 28 days) |
| Part B: Duration of CR, PR and HI | Duration of response in participants with disease response (CR+PR+HI) for hematologic malignancies is time between first documentation of response and disease progression. Duration of response will be determined by the investigator using the revised IWG response criteria. | From first documentation of response up to disease progression (up to 2 years 9 months) |
| Part B: Percentage of Solid Tumors Participants With CR or PR | Disease response in solid tumors was based on best overall response (CR+PR) as determined by investigator using the RECIST version 1.1 criteria. CR: disappearance of all target lesions with any pathological lymph nodes (whether target or nontarget) must have reduction in short axis to <10 millimeter (mm) and disappearance of all nontarget lesions and normalization of tumor marker level with all lymph nodes must be nonpathological in size (<10 mm short axis); PR: At least a 30% decrease from baseline in the sum of diameters of target lesions, taking as reference the baseline sum of diameters and Persistence of one or more nontarget lesion(s) or/and maintenance of tumor marker level above the normal limits. No participants with solid tumors were enrolled in this study. | Cycle 2 Day 22, Cycles 5, 8, and 11 (between Days 15 and 28), and every 6 cycles (up to 2 years 9 months) (Cycle length= 28 days) |
| Chapel Hill |
| North Carolina |
| 27514 |
| United States |
| ICO lHospitalet Hospital Duran i Reynals | LHospitalet de Llobregat | Barcelona | 8908 | Spain |
| Hospital Universitario Vall d'Hebron - PPDS | Barcelona | 8035 | Spain |
| Hospital de San Pedro de Alcantara | Cáceres | 10003 | Spain |
| C.H. Regional Reina Sofia | Córdoba | 14004 | Spain |
| Complejo Asistencial Universitario de Salamanca H. Clinico | Salamanca | 37007 | Spain |
| Hospital Universitario Virgen del Rocio - PPDS | Seville | 41013 | Spain |
| FG001 | Renal Arm | Pevonedistat 20 mg/m^2, infusion, intravenously, once, on Day 1 of Part A in participants with hematologic malignancies, followed by a washout period of approximately 4 to 7 days. Following Part A participants received azacitidine 75 mg/m^2, injection, subcutaneously in Cycle 1 or subcutaneously or intravenously in Cycle 2 and subsequent cycles, once on Day 1 through Day 7 or Day 1 through Day 5, and on Days 8-9 in combination with a starting dose of pevonedistat 10 mg/m^2 to a maximum dose of pevonedistat 15 mg/m^2, infusion, intravenously, once, on Days 1, 3, and 5 in each 28-day treatment cycle in participants with hematologic malignancies in Part B until symptomatic deterioration or PD, discontinuation for any reason, study stopped by the sponsor, or up to 12 cycles. |
| FG002 | Mild Hepatic Arm | Pevonedistat 20 mg/m^2, infusion, intravenously, once, on Day 1 of Part A in participants with hematologic malignancies, followed by a washout period of approximately 4 to 7 days. Following Part A participants received azacitidine 75 mg/m^2, injection, subcutaneously in Cycle 1 or subcutaneously or intravenously in Cycle 2 and subsequent cycles, once on Day 1 through Day 7 or Day 1 through Day 5, and on Days 8 and 9 in combination with a starting dose of pevonedistat 10 mg/m^2 to a maximum dose of pevonedistat 20 mg/m^2, infusion, intravenously, once, on Days 1, 3, and 5 in each 28-day treatment cycle in participants with hematologic malignancies until symptomatic deterioration or PD, discontinuation for any reason, study stopped by the sponsor, or up to 12 cycles. |
| Response-evaluable Population | Response-evaluable population included participants who received at least 1 dose of study drug, had a baseline disease assessment, and had at least 1 postbaseline disease assessment to analyze response. |
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| COMPLETED |
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| NOT COMPLETED |
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| Washout Period : Day 4 to Day 7 |
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| Part B: Day 8 to Day 343 |
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Safety population included all participants who received at least 1 dose of study drug.
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| ID | Title | Description |
|---|---|---|
| BG000 | Control Arm | Pevonedistat 20 milligram per square meter (mg/m^2), infusion, intravenously (IV), once, on Day 1 of Part A in participants with hematologic malignancies, followed by a washout period of approximately 4 to 7 days. Following Part A participants received azacitidine 75 mg/m^2, injection, subcutaneously (SC) in Cycle 1 or SC or IV in Cycle 2 and subsequent cycles, once on Day 1 through Day 7 or Day 1 through Day 5, and on Days 8 and 9 in combination with pevonedistat 20 mg/m^2, infusion, IV, once, on Days 1, 3, and 5 in each 28-day treatment cycle in participants with hematologic malignancies in Part B until symptomatic deterioration or PD, discontinuation for any reason, study stopped by the sponsor, or up to 12 cycles. |
| BG001 | Renal Arm | Pevonedistat 20 mg/m^2, infusion, intravenously, once, on Day 1 of Part A in participants with hematologic malignancies, followed by a washout period of approximately 4 to 7 days. Following Part A participants received azacitidine 75 mg/m^2, injection, subcutaneously in Cycle 1 or subcutaneously or intravenously in Cycle 2 and subsequent cycles, once on Day 1 through Day 7 or Day 1 through Day 5, and on Days 8-9 in combination with a starting dose of pevonedistat 10 mg/m^2 to a maximum dose of pevonedistat 15 mg/m^2, infusion, intravenously, once, on Days 1, 3, and 5 in each 28-day treatment cycle in participants with hematologic malignancies in Part B until symptomatic deterioration or PD, discontinuation for any reason, study stopped by the sponsor, or up to 12 cycles. |
| BG002 | Mild Hepatic Arm | Pevonedistat 20 mg/m^2, infusion, intravenously, once, on Day 1 of Part A in participants with hematologic malignancies, followed by a washout period of approximately 4 to 7 days. Following Part A participants received azacitidine 75 mg/m^2, injection, subcutaneously in Cycle 1 or subcutaneously or intravenously in Cycle 2 and subsequent cycles, once on Day 1 through Day 7 or Day 1 through Day 5, and on Days 8 and 9 in combination with a starting dose of pevonedistat 10 mg/m^2 to a maximum dose of pevonedistat 20 mg/m^2, infusion, intravenously, once, on Days 1, 3, and 5 in each 28-day treatment cycle in participants with hematologic malignancies until symptomatic deterioration or PD, discontinuation for any reason, study stopped by the sponsor, or up to 12 cycles. |
| BG003 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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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| 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 | Part A, AUC∞: Area Under the Plasma Concentration-time Curve From Time Zero to Infinity for Pevonedistat Following a Single Dose | Pharmacokinetic (PK) population included all participants who had sufficient dosing in Part A and Part B Cycle 1, had sufficient concentration-time data to permit reliable estimation of PK parameters, and who had not received any excluded concomitant medications through the completion of Part A. | Posted | Geometric Mean | Geometric Coefficient of Variation | hour*nanogram per milliliter(h*ng/mL) | Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose |
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| Primary | Part A, AUClast: Area Under the Plasma Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration for Pevonedistat Following a Single Dose | PK population included all participants who had sufficient dosing in Part A and Part B Cycle 1, had sufficient concentration-time data to permit reliable estimation of PK parameters, and who had not received any excluded concomitant medications through the completion of Part A. | Posted | Geometric Mean | Geometric Coefficient of Variation | h*ng/mL | Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose |
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| Primary | Part A, Cmax: Maximum Observed Plasma Concentration for Pevonedistat Following a Single Dose | PK population included all participants who had sufficient dosing in Part A and Part B Cycle 1, had sufficient concentration-time data to permit reliable estimation of PK parameters, and who had not received any excluded concomitant medications through the completion of Part A. | Posted | Geometric Mean | Geometric Coefficient of Variation | nanograms per milliliter(ng/mL) | Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose |
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| Secondary | Parts A and B, t1/2z: Terminal Disposition Phase Half-life for Pevonedistat Following Single and Multiple Dose | PK population included all participants who had sufficient dosing in Part A and Part B Cycle 1, had sufficient concentration-time data to permit reliable estimation of PK parameters, and who had not received any excluded concomitant medications through the completion of Part A. Overall number analyzed is the number of participants available for analyses. | Posted | Median | Full Range | hours (h) | Part A: Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose; Part B: Cycle 1 Day 3 pre-dose and at multiple time points (up to 48 hours) post-dose (Cycle length= 28 days) |
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| Secondary | Part B: Cmax: Maximum Observed Plasma Concentration for Pevonedistat Following Multiple Dose | PK population included all participants who had sufficient dosing in Part A and Part B Cycle 1, had sufficient concentration-time data to permit reliable estimation of PK parameters, and who had not received any excluded concomitant medications through the completion of Part A. Overall number analyzed is the number of participants available for analyses. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | Cycle 1 Day 3 pre-dose and at multiple time points (up to 48 hours) post-dose (Cycle length= 28 days) |
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| Secondary | Parts A, fu: Fraction of Unbound Drug in Plasma for Pevonedistat | PK population included all participants who had sufficient dosing in Part A and Part B Cycle 1, had sufficient concentration-time data to permit reliable estimation of PK parameters, and who had not received any excluded concomitant medications through the completion of Part A. Overall number analyzed is the number of participants available for analyses. | Posted | Geometric Mean | Geometric Coefficient of Variation | percentage of plasma fraction unbound | Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose |
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| Secondary | Part B, Cmax: Maximum Observed Plasma Concentration for Azacitidine Following Multiple Dose | PK population included all participants who had sufficient dosing in Part A and Part B Cycle 1, had sufficient concentration-time data to permit reliable estimation of PK parameters, and who had not received any excluded concomitant medications through the completion of Part A. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | Cycle 1 Day 3 pre-dose and at multiple time points (up to 7 hours) post-dose (Cycle length= 28 days) |
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| Secondary | Part B, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Azacitidine Following Multiple Dose | PK population included all participants who had sufficient dosing in Part A and Part B Cycle 1, had sufficient concentration-time data to permit reliable estimation of PK parameters, and who had not received any excluded concomitant medications through the completion of Part A. | Posted | Median | Full Range | hours (h) | Cycle 1 Day 3 pre-dose and at multiple time points (up to 7 hours) post-dose (Cycle length= 28 days) |
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| Secondary | Part B, t1/2z: Terminal Disposition Phase Half-life for Azacitidine Following Multiple-dose | PK population included all participants who had sufficient dosing in Part A and Part B Cycle 1, had sufficient concentration-time data to permit reliable estimation of PK parameters, and who had not received any excluded concomitant medications through the completion of Part A. | Posted | Median | Full Range | hours (h) | Cycle 1 Day 3 pre-dose and at multiple time points (up to 7 hours) post-dose (Cycle length= 28 days) |
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| Secondary | Part B, AUCÏ„: Area Under the Concentration-time Curve From Time Zero to the End of the Dosing Interval for Pevonedistat Following Multiple Dose | PK population included all participants who had sufficient dosing in Part A and Part B Cycle 1, had sufficient concentration-time data to permit reliable estimation of PK parameters, and who had not received any excluded concomitant medications through the completion of Part A. Overall number analyzed is the number of participants available for analyses. | Posted | Geometric Mean | Geometric Coefficient of Variation | h*ng/mL | Cycle 1 Day 3 pre-dose and at multiple time points (up to 48 hours) post-dose (Cycle length= 28 days) |
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| Secondary | Part B, AUCÏ„: Area Under the Concentration-time Curve From Time Zero to the End of the Dosing Interval for Azacitidine Following Multiple Dose | PK population included all participants who had sufficient dosing in Part A and Part B Cycle 1, had sufficient concentration-time data to permit reliable estimation of PK parameters, and who had not received any excluded concomitant medications through the completion of Part A. | Posted | Geometric Mean | Geometric Coefficient of Variation | h*ng/mL | Cycle 1 Day 3 pre-dose and at multiple time points (up to 7 hours) post-dose (Cycle length= 28 days) |
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| Secondary | Parts A and B, CL: Total Clearance for Pevonedistat | PK population included all participants who had sufficient dosing in Part A and Part B Cycle 1, had sufficient concentration-time data to permit reliable estimation of PK parameters, and who had not received any excluded concomitant medications through the completion of Part A. Overall number analyzed is the number of participants available for analyses. | Posted | Geometric Mean | Geometric Coefficient of Variation | liters per hour (L/h) | Part A: Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose; Part B: Cycle 1 Day 3 pre-dose and at multiple time points (up to 48 hours) post-dose (Cycle length is 28 Days) |
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| Secondary | Part B, CL/F: Apparent Clearance for Azacitidine | PK population included all participants who had sufficient dosing in Part A and Part B Cycle 1, had sufficient concentration-time data to permit reliable estimation of PK parameters, and who had not received any excluded concomitant medications through the completion of Part A. | Posted | Geometric Mean | Geometric Coefficient of Variation | L/h | Cycle 1 Day 3 pre-dose and at multiple time points (up to 8 hours) post-dose (Cycle length= 28 days) |
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| Secondary | Part B, CLR: Renal Clearance for Pevonedistat | PK population included all participants who had sufficient dosing in Part A and Part B Cycle 1, had sufficient concentration-time data to permit reliable estimation of PK parameters, and who had not received any excluded concomitant medications through the completion of Part A. Overall number analyzed is the number of participants available for analyses. | Posted | Geometric Mean | Geometric Coefficient of Variation | L/h | Cycle 1 Day 3 pre-dose and at multiple time points (up to 8 hours) post-dose (Cycle length= 28 days) |
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| Secondary | Part B, CLR: Renal Clearance for Azacitidine | PK population included all participants who had sufficient dosing in Part A and Part B Cycle 1, had sufficient concentration-time data to permit reliable estimation of PK parameters, and who had not received any excluded concomitant medications through the completion of Part A. Overall number analyzed is the number of participants available for analyses. | Posted | Geometric Mean | Geometric Coefficient of Variation | L/h | Cycle 1 Day 3 pre-dose and at multiple time points (up to 8 hours) post-dose (Cycle length= 28 days) |
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| Secondary | Parts A and B, Vss: Volume of Distribution at Steady-state of Pevonedistat | PK population included all participants who had sufficient dosing in Part A and Part B Cycle 1, had sufficient concentration-time data to permit reliable estimation of PK parameters, and who had not received any excluded concomitant medications through the completion of Part A. Overall number analyzed is the number of participants available for analyses. | Posted | Geometric Mean | Geometric Coefficient of Variation | Liters (L) | Part A: Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose; Part B: Cycle 1 Day 3 pre-dose and at multiple time points (up to 48 hours) post-dose (Cycle length= 28 days) |
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| Secondary | Part B, Vz/F: Apparent Volume of Distribution of Azacitidine | PK population included all participants who had sufficient dosing in Part A and Part B Cycle 1, had sufficient concentration-time data to permit reliable estimation of PK parameters, and who had not received any excluded concomitant medications through the completion of Part A. Overall number analyzed is the number of participants available for analyses. | Posted | Geometric Mean | Geometric Coefficient of Variation | L | Cycle 1 Day 3 pre-dose and at multiple time points (up to 8 hours) post-dose (Cycle length= 28 days) |
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| Secondary | Part B: Percentage of AML Participants With Complete Response/ Remission (CR) or CR With Incomplete Blood Count Recovery (CRi) or Partial Response (PR) | Disease response in AML are based on international working group (IWG) for diagnosis, standardization of response criteria, treatment outcomes, and reporting standards for therapeutic trials in AML. For AML participants, all CR includes both CR and CRi. CR: morphologic leukemia-free state with absolute neutrophil count (ANC) of greater than (>) 1000 per microliter (/mcL) and platelets of greater than or equal to (>=) 100,000/mcL, and no residual evidence of extramedullary leukemia. CRi: After chemotherapy, some participants fulfill all criteria for CR except for residual neutropenia (less than [<] 1000/mcL) or thrombocytopenia (<100,000/mcL). PR: requires all hematologic values for a CR but with a decrease of at least 50 percent (%) in the percentage of blasts to 5% to 25% in the bone marrow aspirate. A value of less than or equal to (<=) 5% blasts may also be considered a PR if Auer rods are present. | Response-evaluable population included participants who received at least 1 dose of study drug, had a baseline disease assessment, and had at least 1 postbaseline disease assessment to analyze response. Percentages are rounded off to whole number at the nearest decimal. | Posted | Number | percentage of participants | Cycle 2 Day 22, Cycles 5, 8, and 11 (between Days 15 and 28), and every 6 cycles (up to 2 years 9 months) (Cycle length= 28 days) |
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| Secondary | Part B: Percentage of MDS and CMML Participants With CR, PR or Hematologic Improvement (HI) | Disease response in MDS and CMML was based on best overall response (CR+PR+HI) as determined by investigator using revised IWG response criteria for MDS and CMML. CR: morphologic leukemia-free state with absolute neutrophil count (ANC) of greater than (>) 1000 per microliter (/mcL) and platelets of greater than or equal to (>=) 100,000/mcL, and no residual evidence of extramedullary leukemia. PR: requires all hematologic values for a CR but with a decrease of at least 50 percent (%) in the percentage of blasts to 5% to 25% in the bone marrow aspirate. A value of less than or equal to (<=) 5% blasts may also be considered a PR if Auer rods are present. HI: erythropoietic (HI-E): Hemoglobin increase of ≥ 1.5 g/dL untransfused, for red blood cells (RBC) transfusions performed for hemoglobin ≤ 9.0: reduction in RBC units transfused in 8 weeks by ≥ 4 units compared to the number of units transfused in the 8 weeks prior to treatment. No participants with CMML were enrolled in this study. | Response-evaluable population included participants who received at least 1 dose of study drug, had a baseline disease assessment, and had at least 1 postbaseline disease assessment to analyze response. Percentages are rounded off to whole number at the nearest decimal. | Posted | Number | percentage of participants | Cycle 2 Day 22, Cycles 5, 8, and 11 (between Days 15 and 28), and every 6 cycles (up to 2 years 9 months) (Cycle length= 28 days) |
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| Secondary | Part B: Percentage of HR MDS and AML Participants With Overall Response | Overall Response Rate is defined as CR+CRi+PR+HI. CR:≤5% myeloblasts with normal maturation of all bone marrow(BM)cell lines,≥11g/dL Hgb,≥100*10^9/L pl,≥1.0*10^9/L neutrophils,0% blasts in peripheral blood;PR:all CR criteria met except BM blasts ≥50% decrease over pretreatment but still >5%;HI:Hgb increase(inc) ≥1.5g/dL if baseline(BL)<11 g/dL;pl inc≥30*10^9/L if BL>20*10^9/L or inc from <20*10^9/L to >20*10^9/L and by 100%;neutrophil inc by 100%;absolute inc of >0.5*10^9/L if BL<100*10^9/L.For AML-CR:morphologic leukemia-free state >1.0*10^9 neutrophils,≥100*10^9/L pl,transfusion independence,no residual evidence of extramedullary leukemia;CR with incomplete blood count recovery:fulfill CR criteria except residual neutropenia (<1000/μL) or thrombocytopenia (<100,000/μL);PR:all CR hematological values but ≥50% decrease in BM aspirate. | Response-evaluable population included participants who received at least 1 dose of study drug, had a baseline disease assessment, and had at least 1 postbaseline disease assessment to analyze response. Percentages are rounded off to whole number at the nearest decimal. | Posted | Number | percentage of participants | Cycle 2 Day 22, Cycles 5, 8, and 11 (between Days 15 and 28), and every 6 cycles (up to 2 years 9 months) (Cycle length= 28 days) |
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| Secondary | Part B: Duration of CR, PR and HI | Duration of response in participants with disease response (CR+PR+HI) for hematologic malignancies is time between first documentation of response and disease progression. Duration of response will be determined by the investigator using the revised IWG response criteria. | Response-evaluable population included participants who received at least 1 dose of study drug, had a baseline disease assessment, and had at least 1 postbaseline disease assessment to analyze response. Overall number of participants analyzed is the number of participants with disease response (CR+PR+HI) for hematologic malignancies. | Posted | Median | Full Range | days | From first documentation of response up to disease progression (up to 2 years 9 months) |
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| Secondary | Part B: Percentage of Solid Tumors Participants With CR or PR | Disease response in solid tumors was based on best overall response (CR+PR) as determined by investigator using the RECIST version 1.1 criteria. CR: disappearance of all target lesions with any pathological lymph nodes (whether target or nontarget) must have reduction in short axis to <10 millimeter (mm) and disappearance of all nontarget lesions and normalization of tumor marker level with all lymph nodes must be nonpathological in size (<10 mm short axis); PR: At least a 30% decrease from baseline in the sum of diameters of target lesions, taking as reference the baseline sum of diameters and Persistence of one or more nontarget lesion(s) or/and maintenance of tumor marker level above the normal limits. No participants with solid tumors were enrolled in this study. | No participants with solid tumors were enrolled in this study. | Posted | Cycle 2 Day 22, Cycles 5, 8, and 11 (between Days 15 and 28), and every 6 cycles (up to 2 years 9 months) (Cycle length= 28 days) |
|
From the study start up to end of study (up to approximately 2 years 9 months)
At each visit investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by participant or observed by investigator was recorded, irrespective of relation to study treatment. Safety population included all participants who received at least 1 dose of study drug. As pre-specified in protocol and SAP, data for adverse events are reported separately for Part A and Part B based on their renal and/or hepatic function.
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 | Part A: Control Arm | Pevonedistat 20 milligram per square meter (mg/m^2), infusion, intravenously (IV), once, on Day 1 of Part A in participants with hematologic malignancies, followed by a washout period of approximately 4 to 7 days. | 0 | 10 | 0 | 10 | 2 | 10 |
| EG001 | Part A: Renal Arm | Pevonedistat 20 mg/m^2, infusion, intravenously, once, on Day 1 of Part A in participants with renal hematologic malignancies, followed by a washout period of approximately 4 to 7 days. | 0 | 4 | 0 | 4 | 1 | 4 |
| EG002 | Part A: Mild Hepatic Arm | Pevonedistat 20 mg/m^2, infusion, intravenously, once, on Day 1 of Part A in participants with mild hematologic malignancies, followed by a washout period of approximately 4 to 7 days. | 0 | 3 | 0 | 3 | 1 | 3 |
| EG003 | Part B: Control Arm | Following Part A participants received azacitidine 75 mg/m^2, injection, subcutaneously (SC) in Cycle 1 or SC or IV in Cycle 2 and subsequent cycles, once on Day 1 through Day 7 or Day 1 through Day 5, and on Days 8 and 9 in combination with pevonedistat 20 mg/m^2, infusion, IV, once, on Days 1, 3, and 5 in each 28-day treatment cycle in participants with hematologic malignancies in Part B until symptomatic deterioration or PD, discontinuation for any reason, study stopped by the sponsor, or up to 12 cycles. | 2 | 10 | 7 | 10 | 10 | 10 |
| EG004 | Part B: Renal Arm | Following Part A participants received azacitidine 75 mg/m^2, injection, subcutaneously in Cycle 1 or subcutaneously or intravenously in Cycle 2 and subsequent cycles, once on Day 1 through Day 7 or Day 1 through Day 5, and on Days 8-9 in combination with a starting dose of pevonedistat 10 mg/m^2 to a maximum dose of pevonedistat 15 mg/m^2, infusion, intravenously, once, on Days 1, 3, and 5 in each 28-day treatment cycle in participants with renal hematologic malignancies in Part B until symptomatic deterioration or PD, discontinuation for any reason, study stopped by the sponsor, or up to 12 cycles. | 2 | 4 | 3 | 4 | 4 | 4 |
| EG005 | Part B: Mild Hepatic Arm | Following Part A participants received azacitidine 75 mg/m^2, injection, subcutaneously in Cycle 1 or subcutaneously or intravenously in Cycle 2 and subsequent cycles, once on Day 1 through Day 7 or Day 1 through Day 5, and on Days 8 and 9 in combination with a starting dose of pevonedistat 10 mg/m^2 to a maximum dose of pevonedistat 20 mg/m^2, infusion, intravenously, once, on Days 1, 3, and 5 in each 28-day treatment cycle in participants with mild hematologic malignancies in Part B until symptomatic deterioration or PD, discontinuation for any reason, study stopped by the sponsor, or up to 12 cycles. | 0 | 3 | 2 | 3 | 3 | 3 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Acute kidney injury | Renal and urinary disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Acute myeloid leukaemia | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 23.0 | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Bladder transitional cell carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 23.0 | Systematic Assessment |
| |
| Chronic kidney disease | Renal and urinary disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Escherichia bacteraemia | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
| |
| Fatigue | General disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Febrile neutropenia | Blood and lymphatic system disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Haemorrhage intracranial | Nervous system disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Klebsiella bacteraemia | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
| |
| Leukocytosis | Blood and lymphatic system disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Pneumonia pseudomonal | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
| |
| Pneumonia staphylococcal | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Rectal haemorrhage | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Sepsis | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
| |
| Sinusitis | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
| |
| Thyroid gland abscess | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
| |
| Tumour lysis syndrome | Metabolism and nutrition disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
| |
| White blood cell count increased | Investigations | MedDRA 23.0 | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Acidosis | Metabolism and nutrition disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Alanine aminotransferase increased | Investigations | MedDRA 23.0 | Systematic Assessment |
| |
| Allergic cough | Respiratory, thoracic and mediastinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Anaemia | Blood and lymphatic system disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Anal infection | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
| |
| Anxiety | Psychiatric disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Aphthous ulcer | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Aspartate aminotransferase increased | Investigations | MedDRA 23.0 | Systematic Assessment |
| |
| Asthenia | General disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Bladder spasm | Renal and urinary disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Blast cell count increased | Investigations | MedDRA 23.0 | Systematic Assessment |
| |
| Blister | Skin and subcutaneous tissue disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Blood bilirubin increased | Investigations | MedDRA 23.0 | Systematic Assessment |
| |
| Blood creatinine increased | Investigations | MedDRA 23.0 | Systematic Assessment |
| |
| Bone pain | Musculoskeletal and connective tissue disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Bullous haemorrhagic dermatosis | Skin and subcutaneous tissue disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Bursitis | Musculoskeletal and connective tissue disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Catheter site haematoma | General disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Cellulitis | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
| |
| Cognitive disorder | Nervous system disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Conjunctival haemorrhage | Eye disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Contusion | Injury, poisoning and procedural complications | MedDRA 23.0 | Systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Decreased appetite | Metabolism and nutrition disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Depression | Psychiatric disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Dry mouth | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Dry skin | Skin and subcutaneous tissue disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Dyspepsia | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Dysuria | Renal and urinary disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Ear pain | Ear and labyrinth disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Ecchymosis | Skin and subcutaneous tissue disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Erythema | Skin and subcutaneous tissue disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Escherichia bacteraemia | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
| |
| Fall | Injury, poisoning and procedural complications | MedDRA 23.0 | Systematic Assessment |
| |
| Fatigue | General disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Folliculitis | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
| |
| Fungal skin infection | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
| |
| Furuncle | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
| |
| Gingival bleeding | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Gingival pain | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Haematuria | Renal and urinary disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Haemoptysis | Respiratory, thoracic and mediastinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Haemorrhage subcutaneous | Skin and subcutaneous tissue disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Haemorrhoids | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Hallucination | Psychiatric disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Herpes zoster | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
| |
| Hyperphosphataemia | Metabolism and nutrition disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Hypertension | Vascular disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Hypoalbuminaemia | Metabolism and nutrition disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Hypocalcaemia | Metabolism and nutrition disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Hypomagnesaemia | Metabolism and nutrition disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Hyponatraemia | Metabolism and nutrition disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Hypophosphataemia | Metabolism and nutrition disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Hypotension | Vascular disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Hypoxia | Respiratory, thoracic and mediastinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Influenza like illness | General disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Injection site erythema | General disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Injection site nodule | General disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Injection site pain | General disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Insomnia | Psychiatric disorders | MedDRA 23.0 | Systematic Assessment |
| |
| International normalised ratio increased | Investigations | MedDRA 23.0 | Systematic Assessment |
| |
| Keratoacanthoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 23.0 | Systematic Assessment |
| |
| Leukostasis syndrome | Blood and lymphatic system disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Lip blister | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Lip ulceration | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Muscular weakness | Musculoskeletal and connective tissue disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Musculoskeletal chest pain | Musculoskeletal and connective tissue disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Neutropenia | Blood and lymphatic system disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Neutrophil count decreased | Investigations | MedDRA 23.0 | Systematic Assessment |
| |
| Oedema peripheral | General disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Oral candidiasis | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
| |
| Oral herpes | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
| |
| Oral pain | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Oral purpura | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Orthostatic hypotension | Vascular disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Panic attack | Psychiatric disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Panniculitis | Skin and subcutaneous tissue disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Petechiae | Skin and subcutaneous tissue disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Platelet count decreased | Investigations | MedDRA 23.0 | Systematic Assessment |
| |
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Pleuritic pain | Respiratory, thoracic and mediastinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
| |
| Pneumonia fungal | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
| |
| Pneumothorax | Respiratory, thoracic and mediastinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Pollakiuria | Renal and urinary disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Presyncope | Nervous system disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Proctalgia | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Proteinuria | Renal and urinary disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Purpura | Skin and subcutaneous tissue disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Rash maculo-papular | Skin and subcutaneous tissue disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Rhinorrhoea | Respiratory, thoracic and mediastinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Sinus congestion | Respiratory, thoracic and mediastinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Sinus headache | Nervous system disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Sinus tachycardia | Cardiac disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Skin abrasion | Injury, poisoning and procedural complications | MedDRA 23.0 | Systematic Assessment |
| |
| Skin induration | Skin and subcutaneous tissue disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Skin irritation | Skin and subcutaneous tissue disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Skin laceration | Injury, poisoning and procedural complications | MedDRA 23.0 | Systematic Assessment |
| |
| Stomatitis | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Syncope | Nervous system disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Systemic inflammatory response syndrome | General disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Tendonitis | Musculoskeletal and connective tissue disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Tooth infection | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
| |
| Toothache | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Upper respiratory tract infection | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
| |
| Urethral haemorrhage | Renal and urinary disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Urinary incontinence | Renal and urinary disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Urinary tract obstruction | Renal and urinary disorders | MedDRA 23.0 | Systematic Assessment |
| |
| White blood cell count increased | Investigations | MedDRA 23.0 | Systematic Assessment |
|
Research Organization shall not publish any articles or papers nor make any presentations, nor assist any other person in publishing any articles or papers or in making any presentations relating or referring to the Study or any results, data or insights from or any data, information or materials obtained or generated in the performance of its obligations without the prior written consent of Takeda, which consent may be granted or withheld in Takeda's sole discretion.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Study Director | Takeda | +1-877-825-3327 | TrialDisclosures@takeda.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Feb 23, 2022 | Apr 18, 2023 | SAP_001.pdf |
| ID | Term |
|---|---|
| D009190 | Myelodysplastic Syndromes |
| D015477 | Leukemia, Myelomonocytic, Chronic |
| D015470 | Leukemia, Myeloid, Acute |
| D051437 | Renal Insufficiency |
| D008107 | Liver Diseases |
| D009369 | Neoplasms |
| ID | Term |
|---|---|
| D001855 | Bone Marrow Diseases |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D007951 | Leukemia, Myeloid |
| D007938 | Leukemia |
| D009370 | Neoplasms by Histologic Type |
| D054437 | Myelodysplastic-Myeloproliferative Diseases |
| D002908 | Chronic Disease |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D007674 | Kidney Diseases |
| D014570 | Urologic Diseases |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D052801 | Male Urogenital Diseases |
| D004066 | Digestive System Diseases |
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
| Progressive Disease |
|
| Unsatisfactory Therapeutic Response |
|
| Symptomatic Deterioration |
|
| Reason not Specified |
|
| 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 |
|
| Unknown or Not Reported |
|
| Spain |
|
|
|
| Units | Counts |
|---|---|
| Participants |
|
|
| OG003 | Part B: Control Arm: Pevonedistat 10 mg/m^2 + Azacitidine 75 mg/m^2 | Participants with normal renal and hepatic function with hematologic malignancies (MDS and AML) who completed Part A and a 4 to 7 days of washout period received pevonedistat 10 mg/m^2, infusion, IV, once, on Days 1, 3, and 5 in each 28-day treatment cycle in combination with azacitidine 75 mg/m^2, injection, SC in Cycle 1 or SC or IV in Cycle 2 and subsequent cycles, once on Day 1 through Day 7 or Day 1 through Day 5, and on Days 8 and 9 until symptomatic deterioration or PD, discontinuation for any reason, study stopped by the sponsor, or up to 12 cycles. |
| OG004 | Part B: Renal Arm: Pevonedistat 10 mg/m^2 + Azacitidine 75 mg/m^2 | Participants with severe renal impairment with hematologic malignancies (MDS and AML) who completed Part A and a 4 to 7 days of washout period received pevonedistat 10 mg/m^2, infusion, IV, once, on Days 1, 3, and 5 in each 28-day treatment cycle in combination with azacitidine 75 mg/m^2, injection, SC in Cycle 1 or SC or IV in Cycle 2 and subsequent cycles, once on Day 1 through Day 7 or Day 1 through Day 5, and on Days 8-9 until symptomatic deterioration or PD, discontinuation for any reason, study stopped by the sponsor, or up to 12 cycles. |
| OG005 | Part B: Mild Hepatic Arm: Pevonedistat 10 mg/m^2 + Azacitidine 75 mg/m^2 | Participants with mild hepatic impairment with hematologic malignancies (MDS and AML) who completed Part A and a 4 to 7 days of washout period received pevonedistat 10 mg/m^2, infusion, IV, once, on Days 1, 3, and 5 in each 28-day treatment cycle in combination with azacitidine 75 mg/m^2, injection, SC in Cycle 1 or SC or IV in Cycle 2 and subsequent cycles, once on Day 1 through Day 7 or Day 1 through Day 5, and on Days 8-9 until symptomatic deterioration or PD, discontinuation for any reason, study stopped by the sponsor, or up to 12 cycles. |
| OG006 | Part B: Control Arm: Pevonedistat 15 mg/m^2 + Azacitidine 75 mg/m^2 | Participants with normal renal and hepatic function with hematologic malignancies (MDS and AML) who completed Part A and a 4 to 7 days of washout period received pevonedistat 15 mg/m^2, infusion, IV, once, on Days 1, 3, and 5 in each 28-day treatment cycle in combination with azacitidine 75 mg/m^2, injection, SC in Cycle 1 or SC or IV in Cycle 2 and subsequent cycles, once on Day 1 through Day 7 or Day 1 through Day 5, and on Days 8 and 9 until symptomatic deterioration or PD, discontinuation for any reason, study stopped by the sponsor, or up to 12 cycles. |
| OG007 | Part B: Renal Arm: Pevonedistat 15 mg/m^2 + Azacitidine 75 mg/m^2 | Participants with severe renal impairment with hematologic malignancies (MDS and AML) who completed Part A and a 4 to 7 days of washout period received pevonedistat 15 mg/m^2, infusion, IV, once, on Days 1, 3, and 5 in each 28-day treatment cycle in combination with azacitidine 75 mg/m^2, injection, SC in Cycle 1 or SC or IV in Cycle 2 and subsequent cycles, once on Day 1 through Day 7 or Day 1 through Day 5, and on Days 8-9 until symptomatic deterioration or PD, discontinuation for any reason, study stopped by the sponsor, or up to 12 cycles. |
| OG008 | Part B: Mild Hepatic Arm: Pevonedistat 15 mg/m^2 + Azacitidine 75 mg/m^2 | Participants with mild hepatic impairment with hematologic malignancies (MDS and AML) who completed Part A and a 4 to 7 days of washout period received pevonedistat 15 mg/m^2, infusion, IV, once, on Days 1, 3, and 5 in each 28-day treatment cycle in combination with azacitidine 75 mg/m^2, injection, SC in Cycle 1 or SC or IV in Cycle 2 and subsequent cycles, once on Day 1 through Day 7 or Day 1 through Day 5, and on Days 8-9 until symptomatic deterioration or PD, discontinuation for any reason, study stopped by the sponsor, or up to 12 cycles. |
| OG009 | Part B: Control Arm: Pevonedistat 20 mg/m^2 + Azacitidine 75 mg/m^2 | Participants with normal renal and hepatic function with hematologic malignancies (MDS and AML) who completed Part A and a 4 to 7 days of washout period received pevonedistat 20 mg/m^2, infusion, IV, once, on Days 1, 3, and 5 in each 28-day treatment cycle in combination with azacitidine 75 mg/m^2, injection, SC in Cycle 1 or SC or IV in Cycle 2 and subsequent cycles, once on Day 1 through Day 7 or Day 1 through Day 5, and on Days 8 and 9 until symptomatic deterioration or PD, discontinuation for any reason, study stopped by the sponsor, or up to 12 cycles. |
| OG010 | Part B: Renal Arm: Pevonedistat 20 mg/m^2 + Azacitidine 75 mg/m^2 | Participants with severe renal impairment with hematologic malignancies (MDS and AML) who completed Part A and a 4 to 7 days of washout period received pevonedistat 20 mg/m^2, infusion, IV, once, on Days 1, 3, and 5 in each 28-day treatment cycle in combination with azacitidine 75 mg/m^2, injection, SC in Cycle 1 or SC or IV in Cycle 2 and subsequent cycles, once on Day 1 through Day 7 or Day 1 through Day 5, and on Days 8-9 until symptomatic deterioration or PD, discontinuation for any reason, study stopped by the sponsor, or up to 12 cycles. |
| OG011 | Part B: Mild Hepatic Arm: Pevonedistat 20 mg/m^2 + Azacitidine 75 mg/m^2 | Participants with mild hepatic impairment with hematologic malignancies (MDS and AML) who completed Part A and a 4 to 7 days of washout period received pevonedistat 20 mg/m^2, infusion, IV, once, on Days 1, 3, and 5 in each 28-day treatment cycle in combination with azacitidine 75 mg/m^2, injection, SC in Cycle 1 or SC or IV in Cycle 2 and subsequent cycles, once on Day 1 through Day 7 or Day 1 through Day 5, and on Days 8-9 until symptomatic deterioration or PD, discontinuation for any reason, study stopped by the sponsor, or up to 12 cycles. |
|
|
| OG002 | Part B: Mild Hepatic Arm: Pevonedistat 10 mg/m^2 + Azacitidine 75 mg/m^2 | Participants with mild hepatic impairment with hematologic malignancies (MDS and AML) who completed Part A and a 4 to 7 days of washout period received pevonedistat 10 mg/m^2, infusion, IV, once, on Days 1, 3, and 5 in each 28-day treatment cycle in combination with azacitidine 75 mg/m^2, injection, SC in Cycle 1 or SC or IV in Cycle 2 and subsequent cycles, once on Day 1 through Day 7 or Day 1 through Day 5, and on Days 8-9 until symptomatic deterioration or PD, discontinuation for any reason, study stopped by the sponsor, or up to 12 cycles. |
| OG003 | Part B: Control Arm: Pevonedistat 15 mg/m^2 + Azacitidine 75 mg/m^2 | Participants with normal renal and hepatic function with hematologic malignancies (MDS and AML) who completed Part A and a 4 to 7 days of washout period received pevonedistat 15 mg/m^2, infusion, IV, once, on Days 1, 3, and 5 in each 28-day treatment cycle in combination with azacitidine 75 mg/m^2, injection, SC in Cycle 1 or SC or IV in Cycle 2 and subsequent cycles, once on Day 1 through Day 7 or Day 1 through Day 5, and on Days 8 and 9 until symptomatic deterioration or PD, discontinuation for any reason, study stopped by the sponsor, or up to 12 cycles. |
| OG004 | Part B: Renal Arm: Pevonedistat 15 mg/m^2 + Azacitidine 75 mg/m^2 | Participants with severe renal impairment with hematologic malignancies (MDS and AML) who completed Part A and a 4 to 7 days of washout period received pevonedistat 15 mg/m^2, infusion, IV, once, on Days 1, 3, and 5 in each 28-day treatment cycle in combination with azacitidine 75 mg/m^2, injection, SC in Cycle 1 or SC or IV in Cycle 2 and subsequent cycles, once on Day 1 through Day 7 or Day 1 through Day 5, and on Days 8-9 until symptomatic deterioration or PD, discontinuation for any reason, study stopped by the sponsor, or up to 12 cycles. |
| OG005 | Part B: Mild Hepatic Arm: Pevonedistat 15 mg/m^2 + Azacitidine 75 mg/m^2 | Participants with mild hepatic impairment with hematologic malignancies (MDS and AML) who completed Part A and a 4 to 7 days of washout period received pevonedistat 15 mg/m^2, infusion, IV, once, on Days 1, 3, and 5 in each 28-day treatment cycle in combination with azacitidine 75 mg/m^2, injection, SC in Cycle 1 or SC or IV in Cycle 2 and subsequent cycles, once on Day 1 through Day 7 or Day 1 through Day 5, and on Days 8-9 until symptomatic deterioration or PD, discontinuation for any reason, study stopped by the sponsor, or up to 12 cycles. |
| OG006 | Part B: Control Arm: Pevonedistat 20 mg/m^2 + Azacitidine 75 mg/m^2 | Participants with normal renal and hepatic function with hematologic malignancies (MDS and AML) who completed Part A and a 4 to 7 days of washout period received pevonedistat 20 mg/m^2, infusion, IV, once, on Days 1, 3, and 5 in each 28-day treatment cycle in combination with azacitidine 75 mg/m^2, injection, SC in Cycle 1 or SC or IV in Cycle 2 and subsequent cycles, once on Day 1 through Day 7 or Day 1 through Day 5, and on Days 8 and 9 until symptomatic deterioration or PD, discontinuation for any reason, study stopped by the sponsor, or up to 12 cycles. |
| OG007 | Part B: Renal Arm: Pevonedistat 20 mg/m^2 + Azacitidine 75 mg/m^2 | Participants with severe renal impairment with hematologic malignancies (MDS and AML) who completed Part A and a 4 to 7 days of washout period received pevonedistat 20 mg/m^2, infusion, IV, once, on Days 1, 3, and 5 in each 28-day treatment cycle in combination with azacitidine 75 mg/m^2, injection, SC in Cycle 1 or SC or IV in Cycle 2 and subsequent cycles, once on Day 1 through Day 7 or Day 1 through Day 5, and on Days 8-9 until symptomatic deterioration or PD, discontinuation for any reason, study stopped by the sponsor, or up to 12 cycles. |
| OG008 | Part B: Mild Hepatic Arm: Pevonedistat 20 mg/m^2 + Azacitidine 75 mg/m^2 | Participants with mild hepatic impairment with hematologic malignancies (MDS and AML) who completed Part A and a 4 to 7 days of washout period received pevonedistat 20 mg/m^2, infusion, IV, once, on Days 1, 3, and 5 in each 28-day treatment cycle in combination with azacitidine 75 mg/m^2, injection, SC in Cycle 1 or SC or IV in Cycle 2 and subsequent cycles, once on Day 1 through Day 7 or Day 1 through Day 5, and on Days 8-9 until symptomatic deterioration or PD, discontinuation for any reason, study stopped by the sponsor, or up to 12 cycles. |
|
|
|
|
| OG002 | Part B: Mild Hepatic Arm | Pevonedistat 20 mg/m^2, infusion, intravenously, once, on Day 1 of Part A in participants with hematologic malignancies, followed by a washout period of approximately 4 to 7 days. Following Part A participants received azacitidine 75 mg/m^2, injection, subcutaneously in Cycle 1 or subcutaneously or intravenously in Cycle 2 and subsequent cycles, once on Day 1 through Day 7 or Day 1 through Day 5, and on Days 8 and 9 in combination with a starting dose of pevonedistat 10 mg/m^2 to a maximum dose of pevonedistat 20 mg/m^2, infusion, intravenously, once, on Days 1, 3, and 5 in each 28-day treatment cycle in participants with hematologic malignancies until symptomatic deterioration or PD, discontinuation for any reason, study stopped by the sponsor, or up to 12 cycles. |
|
|
| OG002 | Part B: Mild Hepatic Arm | Pevonedistat 20 mg/m^2, infusion, intravenously, once, on Day 1 of Part A in participants with hematologic malignancies, followed by a washout period of approximately 4 to 7 days. Following Part A participants received azacitidine 75 mg/m^2, injection, subcutaneously in Cycle 1 or subcutaneously or intravenously in Cycle 2 and subsequent cycles, once on Day 1 through Day 7 or Day 1 through Day 5, and on Days 8 and 9 in combination with a starting dose of pevonedistat 10 mg/m^2 to a maximum dose of pevonedistat 20 mg/m^2, infusion, intravenously, once, on Days 1, 3, and 5 in each 28-day treatment cycle in participants with hematologic malignancies until symptomatic deterioration or PD, discontinuation for any reason, study stopped by the sponsor, or up to 12 cycles. |
|
|
| OG002 | Part B: Mild Hepatic Arm | Pevonedistat 20 mg/m^2, infusion, intravenously, once, on Day 1 of Part A in participants with hematologic malignancies, followed by a washout period of approximately 4 to 7 days. Following Part A participants received azacitidine 75 mg/m^2, injection, subcutaneously in Cycle 1 or subcutaneously or intravenously in Cycle 2 and subsequent cycles, once on Day 1 through Day 7 or Day 1 through Day 5, and on Days 8 and 9 in combination with a starting dose of pevonedistat 10 mg/m^2 to a maximum dose of pevonedistat 20 mg/m^2, infusion, intravenously, once, on Days 1, 3, and 5 in each 28-day treatment cycle in participants with hematologic malignancies until symptomatic deterioration or PD, discontinuation for any reason, study stopped by the sponsor, or up to 12 cycles. |
|
|
| OG002 | Part B: Mild Hepatic Arm: Pevonedistat 10 mg/m^2 + Azacitidine 75 mg/m^2 | Participants with mild hepatic impairment with hematologic malignancies (MDS and AML) who completed Part A and a 4 to 7 days of washout period received pevonedistat 10 mg/m^2, infusion, IV, once, on Days 1, 3, and 5 in each 28-day treatment cycle in combination with azacitidine 75 mg/m^2, injection, SC in Cycle 1 or SC or IV in Cycle 2 and subsequent cycles, once on Day 1 through Day 7 or Day 1 through Day 5, and on Days 8-9 until symptomatic deterioration or PD, discontinuation for any reason, study stopped by the sponsor, or up to 12 cycles. |
| OG003 | Part B: Control Arm: Pevonedistat 15 mg/m^2 + Azacitidine 75 mg/m^2 | Participants with normal renal and hepatic function with hematologic malignancies (MDS and AML) who completed Part A and a 4 to 7 days of washout period received pevonedistat 15 mg/m^2, infusion, IV, once, on Days 1, 3, and 5 in each 28-day treatment cycle in combination with azacitidine 75 mg/m^2, injection, SC in Cycle 1 or SC or IV in Cycle 2 and subsequent cycles, once on Day 1 through Day 7 or Day 1 through Day 5, and on Days 8 and 9 until symptomatic deterioration or PD, discontinuation for any reason, study stopped by the sponsor, or up to 12 cycles. |
| OG004 | Part B: Renal Arm: Pevonedistat 15 mg/m^2 + Azacitidine 75 mg/m^2 | Participants with severe renal impairment with hematologic malignancies (MDS and AML) who completed Part A and a 4 to 7 days of washout period received pevonedistat 15 mg/m^2, infusion, IV, once, on Days 1, 3, and 5 in each 28-day treatment cycle in combination with azacitidine 75 mg/m^2, injection, SC in Cycle 1 or SC or IV in Cycle 2 and subsequent cycles, once on Day 1 through Day 7 or Day 1 through Day 5, and on Days 8-9 until symptomatic deterioration or PD, discontinuation for any reason, study stopped by the sponsor, or up to 12 cycles. |
| OG005 | Part B: Mild Hepatic Arm: Pevonedistat 15 mg/m^2 + Azacitidine 75 mg/m^2 | Participants with mild hepatic impairment with hematologic malignancies (MDS and AML) who completed Part A and a 4 to 7 days of washout period received pevonedistat 15 mg/m^2, infusion, IV, once, on Days 1, 3, and 5 in each 28-day treatment cycle in combination with azacitidine 75 mg/m^2, injection, SC in Cycle 1 or SC or IV in Cycle 2 and subsequent cycles, once on Day 1 through Day 7 or Day 1 through Day 5, and on Days 8-9 until symptomatic deterioration or PD, discontinuation for any reason, study stopped by the sponsor, or up to 12 cycles. |
| OG006 | Part B: Control Arm: Pevonedistat 20 mg/m^2 + Azacitidine 75 mg/m^2 | Participants with normal renal and hepatic function with hematologic malignancies (MDS and AML) who completed Part A and a 4 to 7 days of washout period received pevonedistat 20 mg/m^2, infusion, IV, once, on Days 1, 3, and 5 in each 28-day treatment cycle in combination with azacitidine 75 mg/m^2, injection, SC in Cycle 1 or SC or IV in Cycle 2 and subsequent cycles, once on Day 1 through Day 7 or Day 1 through Day 5, and on Days 8 and 9 until symptomatic deterioration or PD, discontinuation for any reason, study stopped by the sponsor, or up to 12 cycles. |
| OG007 | Part B: Renal Arm: Pevonedistat 20 mg/m^2 + Azacitidine 75 mg/m^2 | Participants with severe renal impairment with hematologic malignancies (MDS and AML) who completed Part A and a 4 to 7 days of washout period received pevonedistat 20 mg/m^2, infusion, IV, once, on Days 1, 3, and 5 in each 28-day treatment cycle in combination with azacitidine 75 mg/m^2, injection, SC in Cycle 1 or SC or IV in Cycle 2 and subsequent cycles, once on Day 1 through Day 7 or Day 1 through Day 5, and on Days 8-9 until symptomatic deterioration or PD, discontinuation for any reason, study stopped by the sponsor, or up to 12 cycles. |
| OG008 | Part B: Mild Hepatic Arm: Pevonedistat 20 mg/m^2 + Azacitidine 75 mg/m^2 | Participants with mild hepatic impairment with hematologic malignancies (MDS and AML) who completed Part A and a 4 to 7 days of washout period received pevonedistat 20 mg/m^2, infusion, IV, once, on Days 1, 3, and 5 in each 28-day treatment cycle in combination with azacitidine 75 mg/m^2, injection, SC in Cycle 1 or SC or IV in Cycle 2 and subsequent cycles, once on Day 1 through Day 7 or Day 1 through Day 5, and on Days 8-9 until symptomatic deterioration or PD, discontinuation for any reason, study stopped by the sponsor, or up to 12 cycles. |
|
|
| OG002 | Part B: Mild Hepatic Arm | Pevonedistat 20 mg/m^2, infusion, intravenously, once, on Day 1 of Part A in participants with hematologic malignancies, followed by a washout period of approximately 4 to 7 days. Following Part A participants received azacitidine 75 mg/m^2, injection, subcutaneously in Cycle 1 or subcutaneously or intravenously in Cycle 2 and subsequent cycles, once on Day 1 through Day 7 or Day 1 through Day 5, and on Days 8 and 9 in combination with a starting dose of pevonedistat 10 mg/m^2 to a maximum dose of pevonedistat 20 mg/m^2, infusion, intravenously, once, on Days 1, 3, and 5 in each 28-day treatment cycle in participants with hematologic malignancies until symptomatic deterioration or PD, discontinuation for any reason, study stopped by the sponsor, or up to 12 cycles. |
|
|
| OG003 | Part B: Control Arm: Pevonedistat 10 mg/m^2 + Azacitidine 75 mg/m^2 | Participants with normal renal and hepatic function with hematologic malignancies (MDS and AML) who completed Part A and a 4 to 7 days of washout period received pevonedistat 10 mg/m^2, infusion, IV, once, on Days 1, 3, and 5 in each 28-day treatment cycle in combination with azacitidine 75 mg/m^2, injection, SC in Cycle 1 or SC or IV in Cycle 2 and subsequent cycles, once on Day 1 through Day 7 or Day 1 through Day 5, and on Days 8 and 9 until symptomatic deterioration or PD, discontinuation for any reason, study stopped by the sponsor, or up to 12 cycles. |
| OG004 | Part B: Renal Arm: Pevonedistat 10 mg/m^2 + Azacitidine 75 mg/m^2 | Participants with severe renal impairment with hematologic malignancies (MDS and AML) who completed Part A and a 4 to 7 days of washout period received pevonedistat 10 mg/m^2, infusion, IV, once, on Days 1, 3, and 5 in each 28-day treatment cycle in combination with azacitidine 75 mg/m^2, injection, SC in Cycle 1 or SC or IV in Cycle 2 and subsequent cycles, once on Day 1 through Day 7 or Day 1 through Day 5, and on Days 8-9 until symptomatic deterioration or PD, discontinuation for any reason, study stopped by the sponsor, or up to 12 cycles. |
| OG005 | Part B: Mild Hepatic Arm: Pevonedistat 10 mg/m^2 + Azacitidine 75 mg/m^2 | Participants with mild hepatic impairment with hematologic malignancies (MDS and AML) who completed Part A and a 4 to 7 days of washout period received pevonedistat 10 mg/m^2, infusion, IV, once, on Days 1, 3, and 5 in each 28-day treatment cycle in combination with azacitidine 75 mg/m^2, injection, SC in Cycle 1 or SC or IV in Cycle 2 and subsequent cycles, once on Day 1 through Day 7 or Day 1 through Day 5, and on Days 8-9 until symptomatic deterioration or PD, discontinuation for any reason, study stopped by the sponsor, or up to 12 cycles. |
| OG006 | Part B: Control Arm: Pevonedistat 15 mg/m^2 + Azacitidine 75 mg/m^2 | Participants with normal renal and hepatic function with hematologic malignancies (MDS and AML) who completed Part A and a 4 to 7 days of washout period received pevonedistat 15 mg/m^2, infusion, IV, once, on Days 1, 3, and 5 in each 28-day treatment cycle in combination with azacitidine 75 mg/m^2, injection, SC in Cycle 1 or SC or IV in Cycle 2 and subsequent cycles, once on Day 1 through Day 7 or Day 1 through Day 5, and on Days 8 and 9 until symptomatic deterioration or PD, discontinuation for any reason, study stopped by the sponsor, or up to 12 cycles. |
| OG007 | Part B: Renal Arm: Pevonedistat 15 mg/m^2 + Azacitidine 75 mg/m^2 | Participants with severe renal impairment with hematologic malignancies (MDS and AML) who completed Part A and a 4 to 7 days of washout period received pevonedistat 15 mg/m^2, infusion, IV, once, on Days 1, 3, and 5 in each 28-day treatment cycle in combination with azacitidine 75 mg/m^2, injection, SC in Cycle 1 or SC or IV in Cycle 2 and subsequent cycles, once on Day 1 through Day 7 or Day 1 through Day 5, and on Days 8-9 until symptomatic deterioration or PD, discontinuation for any reason, study stopped by the sponsor, or up to 12 cycles. |
| OG008 | Part B: Mild Hepatic Arm: Pevonedistat 15 mg/m^2 + Azacitidine 75 mg/m^2 | Participants with mild hepatic impairment with hematologic malignancies (MDS and AML) who completed Part A and a 4 to 7 days of washout period received pevonedistat 15 mg/m^2, infusion, IV, once, on Days 1, 3, and 5 in each 28-day treatment cycle in combination with azacitidine 75 mg/m^2, injection, SC in Cycle 1 or SC or IV in Cycle 2 and subsequent cycles, once on Day 1 through Day 7 or Day 1 through Day 5, and on Days 8-9 until symptomatic deterioration or PD, discontinuation for any reason, study stopped by the sponsor, or up to 12 cycles. |
| OG009 | Part B: Control Arm: Pevonedistat 20 mg/m^2 + Azacitidine 75 mg/m^2 | Participants with normal renal and hepatic function with hematologic malignancies (MDS and AML) who completed Part A and a 4 to 7 days of washout period received pevonedistat 20 mg/m^2, infusion, IV, once, on Days 1, 3, and 5 in each 28-day treatment cycle in combination with azacitidine 75 mg/m^2, injection, SC in Cycle 1 or SC or IV in Cycle 2 and subsequent cycles, once on Day 1 through Day 7 or Day 1 through Day 5, and on Days 8 and 9 until symptomatic deterioration or PD, discontinuation for any reason, study stopped by the sponsor, or up to 12 cycles. |
| OG010 | Part B: Renal Arm: Pevonedistat 20 mg/m^2 + Azacitidine 75 mg/m^2 | Participants with severe renal impairment with hematologic malignancies (MDS and AML) who completed Part A and a 4 to 7 days of washout period received pevonedistat 20 mg/m^2, infusion, IV, once, on Days 1, 3, and 5 in each 28-day treatment cycle in combination with azacitidine 75 mg/m^2, injection, SC in Cycle 1 or SC or IV in Cycle 2 and subsequent cycles, once on Day 1 through Day 7 or Day 1 through Day 5, and on Days 8-9 until symptomatic deterioration or PD, discontinuation for any reason, study stopped by the sponsor, or up to 12 cycles. |
| OG011 | Part B: Mild Hepatic Arm: Pevonedistat 20 mg/m^2 + Azacitidine 75 mg/m^2 | Participants with mild hepatic impairment with hematologic malignancies (MDS and AML) who completed Part A and a 4 to 7 days of washout period received pevonedistat 20 mg/m^2, infusion, IV, once, on Days 1, 3, and 5 in each 28-day treatment cycle in combination with azacitidine 75 mg/m^2, injection, SC in Cycle 1 or SC or IV in Cycle 2 and subsequent cycles, once on Day 1 through Day 7 or Day 1 through Day 5, and on Days 8-9 until symptomatic deterioration or PD, discontinuation for any reason, study stopped by the sponsor, or up to 12 cycles. |
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| OG002 | Part B: Mild Hepatic Arm | Pevonedistat 20 mg/m^2, infusion, intravenously, once, on Day 1 of Part A in participants with hematologic malignancies, followed by a washout period of approximately 4 to 7 days. Following Part A participants received azacitidine 75 mg/m^2, injection, subcutaneously in Cycle 1 or subcutaneously or intravenously in Cycle 2 and subsequent cycles, once on Day 1 through Day 7 or Day 1 through Day 5, and on Days 8 and 9 in combination with a starting dose of pevonedistat 10 mg/m^2 to a maximum dose of pevonedistat 20 mg/m^2, infusion, intravenously, once, on Days 1, 3, and 5 in each 28-day treatment cycle in participants with hematologic malignancies until symptomatic deterioration or PD, discontinuation for any reason, study stopped by the sponsor, or up to 12 cycles. |
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| OG002 | Part B: Mild Hepatic Arm: Pevonedistat 10 mg/m^2 + Azacitidine 75 mg/m^2 | Participants with mild hepatic impairment with hematologic malignancies (MDS and AML) who completed Part A and a 4 to 7 days of washout period received pevonedistat 10 mg/m^2, infusion, IV, once, on Days 1, 3, and 5 in each 28-day treatment cycle in combination with azacitidine 75 mg/m^2, injection, SC in Cycle 1 or SC or IV in Cycle 2 and subsequent cycles, once on Day 1 through Day 7 or Day 1 through Day 5, and on Days 8-9 until symptomatic deterioration or PD, discontinuation for any reason, study stopped by the sponsor, or up to 12 cycles. |
| OG003 | Part B: Control Arm: Pevonedistat 15 mg/m^2 + Azacitidine 75 mg/m^2 | Participants with normal renal and hepatic function with hematologic malignancies (MDS and AML) who completed Part A and a 4 to 7 days of washout period received pevonedistat 15 mg/m^2, infusion, IV, once, on Days 1, 3, and 5 in each 28-day treatment cycle in combination with azacitidine 75 mg/m^2, injection, SC in Cycle 1 or SC or IV in Cycle 2 and subsequent cycles, once on Day 1 through Day 7 or Day 1 through Day 5, and on Days 8 and 9 until symptomatic deterioration or PD, discontinuation for any reason, study stopped by the sponsor, or up to 12 cycles. |
| OG004 | Part B: Renal Arm: Pevonedistat 15 mg/m^2 + Azacitidine 75 mg/m^2 | Participants with severe renal impairment with hematologic malignancies (MDS and AML) who completed Part A and a 4 to 7 days of washout period received pevonedistat 15 mg/m^2, infusion, IV, once, on Days 1, 3, and 5 in each 28-day treatment cycle in combination with azacitidine 75 mg/m^2, injection, SC in Cycle 1 or SC or IV in Cycle 2 and subsequent cycles, once on Day 1 through Day 7 or Day 1 through Day 5, and on Days 8-9 until symptomatic deterioration or PD, discontinuation for any reason, study stopped by the sponsor, or up to 12 cycles. |
| OG005 | Part B: Mild Hepatic Arm: Pevonedistat 15 mg/m^2 + Azacitidine 75 mg/m^2 | Participants with mild hepatic impairment with hematologic malignancies (MDS and AML) who completed Part A and a 4 to 7 days of washout period received pevonedistat 15 mg/m^2, infusion, IV, once, on Days 1, 3, and 5 in each 28-day treatment cycle in combination with azacitidine 75 mg/m^2, injection, SC in Cycle 1 or SC or IV in Cycle 2 and subsequent cycles, once on Day 1 through Day 7 or Day 1 through Day 5, and on Days 8-9 until symptomatic deterioration or PD, discontinuation for any reason, study stopped by the sponsor, or up to 12 cycles. |
| OG006 | Part B: Control Arm: Pevonedistat 20 mg/m^2 + Azacitidine 75 mg/m^2 | Participants with normal renal and hepatic function with hematologic malignancies (MDS and AML) who completed Part A and a 4 to 7 days of washout period received pevonedistat 20 mg/m^2, infusion, IV, once, on Days 1, 3, and 5 in each 28-day treatment cycle in combination with azacitidine 75 mg/m^2, injection, SC in Cycle 1 or SC or IV in Cycle 2 and subsequent cycles, once on Day 1 through Day 7 or Day 1 through Day 5, and on Days 8 and 9 until symptomatic deterioration or PD, discontinuation for any reason, study stopped by the sponsor, or up to 12 cycles. |
| OG007 | Part B: Renal Arm: Pevonedistat 20 mg/m^2 + Azacitidine 75 mg/m^2 | Participants with severe renal impairment with hematologic malignancies (MDS and AML) who completed Part A and a 4 to 7 days of washout period received pevonedistat 20 mg/m^2, infusion, IV, once, on Days 1, 3, and 5 in each 28-day treatment cycle in combination with azacitidine 75 mg/m^2, injection, SC in Cycle 1 or SC or IV in Cycle 2 and subsequent cycles, once on Day 1 through Day 7 or Day 1 through Day 5, and on Days 8-9 until symptomatic deterioration or PD, discontinuation for any reason, study stopped by the sponsor, or up to 12 cycles. |
| OG008 | Part B: Mild Hepatic Arm: Pevonedistat 20 mg/m^2 + Azacitidine 75 mg/m^2 | Participants with mild hepatic impairment with hematologic malignancies (MDS and AML) who completed Part A and a 4 to 7 days of washout period received pevonedistat 20 mg/m^2, infusion, IV, once, on Days 1, 3, and 5 in each 28-day treatment cycle in combination with azacitidine 75 mg/m^2, injection, SC in Cycle 1 or SC or IV in Cycle 2 and subsequent cycles, once on Day 1 through Day 7 or Day 1 through Day 5, and on Days 8-9 until symptomatic deterioration or PD, discontinuation for any reason, study stopped by the sponsor, or up to 12 cycles. |
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| OG002 | Part B: Mild Hepatic Arm | Pevonedistat 20 mg/m^2, infusion, intravenously, once, on Day 1 of Part A in participants with hematologic malignancies, followed by a washout period of approximately 4 to 7 days. Following Part A participants received azacitidine 75 mg/m^2, injection, subcutaneously in Cycle 1 or subcutaneously or intravenously in Cycle 2 and subsequent cycles, once on Day 1 through Day 7 or Day 1 through Day 5, and on Days 8 and 9 in combination with a starting dose of pevonedistat 10 mg/m^2 to a maximum dose of pevonedistat 20 mg/m^2, infusion, intravenously, once, on Days 1, 3, and 5 in each 28-day treatment cycle in participants with hematologic malignancies until symptomatic deterioration or PD, discontinuation for any reason, study stopped by the sponsor, or up to 12 cycles. |
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| OG003 | Part B: Control Arm: Pevonedistat 10 mg/m^2 + Azacitidine 75 mg/m^2 | Participants with normal renal and hepatic function with hematologic malignancies (MDS and AML) who completed Part A and a 4 to 7 days of washout period received pevonedistat 10 mg/m^2, infusion, IV, once, on Days 1, 3, and 5 in each 28-day treatment cycle in combination with azacitidine 75 mg/m^2, injection, SC in Cycle 1 or SC or IV in Cycle 2 and subsequent cycles, once on Day 1 through Day 7 or Day 1 through Day 5, and on Days 8 and 9 until symptomatic deterioration or PD, discontinuation for any reason, study stopped by the sponsor, or up to 12 cycles. |
| OG004 | Part B: Renal Arm: Pevonedistat 10 mg/m^2 + Azacitidine 75 mg/m^2 | Participants with severe renal impairment with hematologic malignancies (MDS and AML) who completed Part A and a 4 to 7 days of washout period received pevonedistat 10 mg/m^2, infusion, IV, once, on Days 1, 3, and 5 in each 28-day treatment cycle in combination with azacitidine 75 mg/m^2, injection, SC in Cycle 1 or SC or IV in Cycle 2 and subsequent cycles, once on Day 1 through Day 7 or Day 1 through Day 5, and on Days 8-9 until symptomatic deterioration or PD, discontinuation for any reason, study stopped by the sponsor, or up to 12 cycles. |
| OG005 | Part B: Mild Hepatic Arm: Pevonedistat 10 mg/m^2 + Azacitidine 75 mg/m^2 | Participants with mild hepatic impairment with hematologic malignancies (MDS and AML) who completed Part A and a 4 to 7 days of washout period received pevonedistat 10 mg/m^2, infusion, IV, once, on Days 1, 3, and 5 in each 28-day treatment cycle in combination with azacitidine 75 mg/m^2, injection, SC in Cycle 1 or SC or IV in Cycle 2 and subsequent cycles, once on Day 1 through Day 7 or Day 1 through Day 5, and on Days 8-9 until symptomatic deterioration or PD, discontinuation for any reason, study stopped by the sponsor, or up to 12 cycles. |
| OG006 | Part B: Control Arm: Pevonedistat 15 mg/m^2 + Azacitidine 75 mg/m^2 | Participants with normal renal and hepatic function with hematologic malignancies (MDS and AML) who completed Part A and a 4 to 7 days of washout period received pevonedistat 15 mg/m^2, infusion, IV, once, on Days 1, 3, and 5 in each 28-day treatment cycle in combination with azacitidine 75 mg/m^2, injection, SC in Cycle 1 or SC or IV in Cycle 2 and subsequent cycles, once on Day 1 through Day 7 or Day 1 through Day 5, and on Days 8 and 9 until symptomatic deterioration or PD, discontinuation for any reason, study stopped by the sponsor, or up to 12 cycles. |
| OG007 | Part B: Renal Arm: Pevonedistat 15 mg/m^2 + Azacitidine 75 mg/m^2 | Participants with severe renal impairment with hematologic malignancies (MDS and AML) who completed Part A and a 4 to 7 days of washout period received pevonedistat 15 mg/m^2, infusion, IV, once, on Days 1, 3, and 5 in each 28-day treatment cycle in combination with azacitidine 75 mg/m^2, injection, SC in Cycle 1 or SC or IV in Cycle 2 and subsequent cycles, once on Day 1 through Day 7 or Day 1 through Day 5, and on Days 8-9 until symptomatic deterioration or PD, discontinuation for any reason, study stopped by the sponsor, or up to 12 cycles. |
| OG008 | Part B: Mild Hepatic Arm: Pevonedistat 15 mg/m^2 + Azacitidine 75 mg/m^2 | Participants with mild hepatic impairment with hematologic malignancies (MDS and AML) who completed Part A and a 4 to 7 days of washout period received pevonedistat 15 mg/m^2, infusion, IV, once, on Days 1, 3, and 5 in each 28-day treatment cycle in combination with azacitidine 75 mg/m^2, injection, SC in Cycle 1 or SC or IV in Cycle 2 and subsequent cycles, once on Day 1 through Day 7 or Day 1 through Day 5, and on Days 8-9 until symptomatic deterioration or PD, discontinuation for any reason, study stopped by the sponsor, or up to 12 cycles. |
| OG009 | Part B: Control Arm: Pevonedistat 20 mg/m^2 + Azacitidine 75 mg/m^2 | Participants with normal renal and hepatic function with hematologic malignancies (MDS and AML) who completed Part A and a 4 to 7 days of washout period received pevonedistat 20 mg/m^2, infusion, IV, once, on Days 1, 3, and 5 in each 28-day treatment cycle in combination with azacitidine 75 mg/m^2, injection, SC in Cycle 1 or SC or IV in Cycle 2 and subsequent cycles, once on Day 1 through Day 7 or Day 1 through Day 5, and on Days 8 and 9 until symptomatic deterioration or PD, discontinuation for any reason, study stopped by the sponsor, or up to 12 cycles. |
| OG010 | Part B: Renal Arm: Pevonedistat 20 mg/m^2 + Azacitidine 75 mg/m^2 | Participants with severe renal impairment with hematologic malignancies (MDS and AML) who completed Part A and a 4 to 7 days of washout period received pevonedistat 20 mg/m^2, infusion, IV, once, on Days 1, 3, and 5 in each 28-day treatment cycle in combination with azacitidine 75 mg/m^2, injection, SC in Cycle 1 or SC or IV in Cycle 2 and subsequent cycles, once on Day 1 through Day 7 or Day 1 through Day 5, and on Days 8-9 until symptomatic deterioration or PD, discontinuation for any reason, study stopped by the sponsor, or up to 12 cycles. |
| OG011 | Part B: Mild Hepatic Arm: Pevonedistat 20 mg/m^2 + Azacitidine 75 mg/m^2 | Participants with mild hepatic impairment with hematologic malignancies (MDS and AML) who completed Part A and a 4 to 7 days of washout period received pevonedistat 20 mg/m^2, infusion, IV, once, on Days 1, 3, and 5 in each 28-day treatment cycle in combination with azacitidine 75 mg/m^2, injection, SC in Cycle 1 or SC or IV in Cycle 2 and subsequent cycles, once on Day 1 through Day 7 or Day 1 through Day 5, and on Days 8-9 until symptomatic deterioration or PD, discontinuation for any reason, study stopped by the sponsor, or up to 12 cycles. |
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| OG002 | Part B: Mild Hepatic Arm | Pevonedistat 20 mg/m^2, infusion, intravenously, once, on Day 1 of Part A in participants with hematologic malignancies, followed by a washout period of approximately 4 to 7 days. Following Part A participants received azacitidine 75 mg/m^2, injection, subcutaneously in Cycle 1 or subcutaneously or intravenously in Cycle 2 and subsequent cycles, once on Day 1 through Day 7 or Day 1 through Day 5, and on Days 8 and 9 in combination with a starting dose of pevonedistat 10 mg/m^2 to a maximum dose of pevonedistat 20 mg/m^2, infusion, intravenously, once, on Days 1, 3, and 5 in each 28-day treatment cycle in participants with hematologic malignancies until symptomatic deterioration or PD, discontinuation for any reason, study stopped by the sponsor, or up to 12 cycles. |
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| OG001 | Part B: Renal Arm | Pevonedistat 20 mg/m^2, infusion, intravenously, once, on Day 1 of Part A in participants with hematologic malignancies, followed by a washout period of approximately 4 to 7 days. Following Part A participants received azacitidine 75 mg/m^2, injection, subcutaneously in Cycle 1 or subcutaneously or intravenously in Cycle 2 and subsequent cycles, once on Day 1 through Day 7 or Day 1 through Day 5, and on Days 8-9 in combination with a starting dose of pevonedistat 10 mg/m^2 to a maximum dose of pevonedistat 15 mg/m^2, infusion, intravenously, once, on Days 1, 3, and 5 in each 28-day treatment cycle in participants with hematologic malignancies in Part B until symptomatic deterioration or PD, discontinuation for any reason, study stopped by the sponsor, or up to 12 cycles. |
| OG002 | Part B: Mild Hepatic Arm | Pevonedistat 20 mg/m^2, infusion, intravenously, once, on Day 1 of Part A in participants with hematologic malignancies, followed by a washout period of approximately 4 to 7 days. Following Part A participants received azacitidine 75 mg/m^2, injection, subcutaneously in Cycle 1 or subcutaneously or intravenously in Cycle 2 and subsequent cycles, once on Day 1 through Day 7 or Day 1 through Day 5, and on Days 8 and 9 in combination with a starting dose of pevonedistat 10 mg/m^2 to a maximum dose of pevonedistat 20 mg/m^2, infusion, intravenously, once, on Days 1, 3, and 5 in each 28-day treatment cycle in participants with hematologic malignancies until symptomatic deterioration or PD, discontinuation for any reason, study stopped by the sponsor, or up to 12 cycles. |
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| OG001 | Part B: Renal Arm | Pevonedistat 20 mg/m^2, infusion, intravenously, once, on Day 1 of Part A in participants with hematologic malignancies, followed by a washout period of approximately 4 to 7 days. Following Part A participants received azacitidine 75 mg/m^2, injection, subcutaneously in Cycle 1 or subcutaneously or intravenously in Cycle 2 and subsequent cycles, once on Day 1 through Day 7 or Day 1 through Day 5, and on Days 8-9 in combination with a starting dose of pevonedistat 10 mg/m^2 to a maximum dose of pevonedistat 15 mg/m^2, infusion, intravenously, once, on Days 1, 3, and 5 in each 28-day treatment cycle in participants with hematologic malignancies in Part B until symptomatic deterioration or PD, discontinuation for any reason, study stopped by the sponsor, or up to 12 cycles. |
| OG002 | Part B: Mild Hepatic Arm | Pevonedistat 20 mg/m^2, infusion, intravenously, once, on Day 1 of Part A in participants with hematologic malignancies, followed by a washout period of approximately 4 to 7 days. Following Part A participants received azacitidine 75 mg/m^2, injection, subcutaneously in Cycle 1 or subcutaneously or intravenously in Cycle 2 and subsequent cycles, once on Day 1 through Day 7 or Day 1 through Day 5, and on Days 8 and 9 in combination with a starting dose of pevonedistat 10 mg/m^2 to a maximum dose of pevonedistat 20 mg/m^2, infusion, intravenously, once, on Days 1, 3, and 5 in each 28-day treatment cycle in participants with hematologic malignancies until symptomatic deterioration or PD, discontinuation for any reason, study stopped by the sponsor, or up to 12 cycles. |
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| OG001 | Part B: Renal Arm | Pevonedistat 20 mg/m^2, infusion, intravenously, once, on Day 1 of Part A in participants with hematologic malignancies, followed by a washout period of approximately 4 to 7 days. Following Part A participants received azacitidine 75 mg/m^2, injection, subcutaneously in Cycle 1 or subcutaneously or intravenously in Cycle 2 and subsequent cycles, once on Day 1 through Day 7 or Day 1 through Day 5, and on Days 8-9 in combination with a starting dose of pevonedistat 10 mg/m^2 to a maximum dose of pevonedistat 15 mg/m^2, infusion, intravenously, once, on Days 1, 3, and 5 in each 28-day treatment cycle in participants with hematologic malignancies in Part B until symptomatic deterioration or PD, discontinuation for any reason, study stopped by the sponsor, or up to 12 cycles. |
| OG002 | Part B: Mild Hepatic Arm | Pevonedistat 20 mg/m^2, infusion, intravenously, once, on Day 1 of Part A in participants with hematologic malignancies, followed by a washout period of approximately 4 to 7 days. Following Part A participants received azacitidine 75 mg/m^2, injection, subcutaneously in Cycle 1 or subcutaneously or intravenously in Cycle 2 and subsequent cycles, once on Day 1 through Day 7 or Day 1 through Day 5, and on Days 8 and 9 in combination with a starting dose of pevonedistat 10 mg/m^2 to a maximum dose of pevonedistat 20 mg/m^2, infusion, intravenously, once, on Days 1, 3, and 5 in each 28-day treatment cycle in participants with hematologic malignancies until symptomatic deterioration or PD, discontinuation for any reason, study stopped by the sponsor, or up to 12 cycles. |
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Pevonedistat 20 mg/m^2, infusion, intravenously, once, on Day 1 of Part A in participants with hematologic malignancies, followed by a washout period of approximately 4 to 7 days. Following Part A participants received azacitidine 75 mg/m^2, injection, subcutaneously in Cycle 1 or subcutaneously or intravenously in Cycle 2 and subsequent cycles, once on Day 1 through Day 7 or Day 1 through Day 5, and on Days 8-9 in combination with a starting dose of pevonedistat 10 mg/m^2 to a maximum dose of pevonedistat 15 mg/m^2, infusion, intravenously, once, on Days 1, 3, and 5 in each 28-day treatment cycle in participants with hematologic malignancies in Part B until symptomatic deterioration or PD, discontinuation for any reason, study stopped by the sponsor, or up to 12 cycles. |
| OG002 | Part B: Mild Hepatic Arm | Pevonedistat 20 mg/m^2, infusion, intravenously, once, on Day 1 of Part A in participants with hematologic malignancies, followed by a washout period of approximately 4 to 7 days. Following Part A participants received azacitidine 75 mg/m^2, injection, subcutaneously in Cycle 1 or subcutaneously or intravenously in Cycle 2 and subsequent cycles, once on Day 1 through Day 7 or Day 1 through Day 5, and on Days 8 and 9 in combination with a starting dose of pevonedistat 10 mg/m^2 to a maximum dose of pevonedistat 20 mg/m^2, infusion, intravenously, once, on Days 1, 3, and 5 in each 28-day treatment cycle in participants with hematologic malignancies until symptomatic deterioration or PD, discontinuation for any reason, study stopped by the sponsor, or up to 12 cycles. |
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| OG001 | Part B: Renal Arm | Pevonedistat 20 mg/m^2, infusion, intravenously, once, on Day 1 of Part A in participants with hematologic malignancies, followed by a washout period of approximately 4 to 7 days. Following Part A participants received azacitidine 75 mg/m^2, injection, subcutaneously in Cycle 1 or subcutaneously or intravenously in Cycle 2 and subsequent cycles, once on Day 1 through Day 7 or Day 1 through Day 5, and on Days 8-9 in combination with a starting dose of pevonedistat 10 mg/m^2 to a maximum dose of pevonedistat 15 mg/m^2, infusion, intravenously, once, on Days 1, 3, and 5 in each 28-day treatment cycle in participants with hematologic malignancies in Part B until symptomatic deterioration or PD, discontinuation for any reason, study stopped by the sponsor, or up to 12 cycles. |
| OG002 | Part B: Mild Hepatic Arm | Pevonedistat 20 mg/m^2, infusion, intravenously, once, on Day 1 of Part A in participants with hematologic malignancies, followed by a washout period of approximately 4 to 7 days. Following Part A participants received azacitidine 75 mg/m^2, injection, subcutaneously in Cycle 1 or subcutaneously or intravenously in Cycle 2 and subsequent cycles, once on Day 1 through Day 7 or Day 1 through Day 5, and on Days 8 and 9 in combination with a starting dose of pevonedistat 10 mg/m^2 to a maximum dose of pevonedistat 20 mg/m^2, infusion, intravenously, once, on Days 1, 3, and 5 in each 28-day treatment cycle in participants with hematologic malignancies until symptomatic deterioration or PD, discontinuation for any reason, study stopped by the sponsor, or up to 12 cycles. |
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