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Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/study/NCT03850535
Registration number
NCT03850535
Ethics application status
Date submitted
20/02/2019
Date registered
21/02/2019
Titles & IDs
Public title
A Study Evaluating the Safety and Efficacy of Idasanutlin in Combination With Cytarabine and Daunorubicin in Patients Newly Diagnosed With Acute Myeloid Leukemia (AML) and the Safety and Efficacy of Idasanutlin in the Maintenance of First AML Complete Remission
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Scientific title
A Phase Ib/II Study Evaluating the Safety and Efficacy of Idasanutlin in Combination With Cytarabine and Daunorubicin in Patients Newly Diagnosed With Acute Myeloid Leukemia (AML) and the Safety and Efficacy of Idasanutlin in the Maintenance of First AML Complete Remission
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Secondary ID [1]
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2018-002964-25
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Secondary ID [2]
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GO40800
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Universal Trial Number (UTN)
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Trial acronym
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
Acute Myeloid Leukemia
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Condition category
Condition code
Cancer
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Leukaemia - Acute leukaemia
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Cancer
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Leukaemia - Chronic leukaemia
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Cancer
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Children's - Leukaemia & Lymphoma
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Intervention/exposure
Study type
Interventional
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Description of intervention(s) / exposure
Treatment: Drugs - Idasanutlin
Treatment: Drugs - Cytarabine
Treatment: Drugs - Daunorubicin
Treatment: Surgery - Allogeneic Hematopoietic Stem Cell Transplant (Allo-HSCT)
Experimental: Dose-Escalation Phase - Participants with newly diagnosed, previously untreated, favorable or intermediate risk AML (according to European LeukemiaNet \[ELN\] 2017 criteria) will undergo the treatment sequence of induction, consolidation, and maintenance. For induction, participants will be treated with idasanutlin plus cytarabine and daunorubicin. At the investigator's discretion for consolidation, either participants will be treated with idasanutlin and cytarabine or they will undergo Allo-HSCT. For maintenance, participants will be treated with single-agent idasanutlin.
Experimental: Post-Consolidation Phase - Participants who are idasanutlin treatment-naive, had received induction and chemotherapy consolidation for AML outside of the study, and were in minimal residual disease (MRD)-positive remission after induction will be enrolled in this cohort to receive maintenance treatment with single-agent idasanutlin.
Experimental: Expansion Phase: Favorable/Intermediate-Risk AML - Participants with newly diagnosed, previously untreated, favorable or intermediate risk AML (according to ELN 2017 criteria) will undergo the treatment sequence of induction, consolidation, and maintenance. For induction, participants will be treated with idasanutlin (at the recommended Phase 2 dose) plus cytarabine and daunorubicin. At the investigator's discretion for consolidation, either participants will be treated with idasanutlin and cytarabine or they will undergo Allo-HSCT. For maintenance, participants will be treated with single-agent idasanutlin.
Experimental: Expansion Phase: High-Risk AML - Participants with newly diagnosed, previously untreated, high-risk AML (defined as adverse risk according to ELN 2017 criteria, and secondary AML) will undergo the treatment sequence of induction, consolidation, and maintenance. For induction, participants will be treated with idasanutlin (at the recommended Phase 2 dose) plus cytarabine and daunorubicin. At the investigator's discretion for consolidation, either participants will be treated with idasanutlin and cytarabine or they will undergo Allo-HSCT. For maintenance, participants will be treated with single-agent idasanutlin.
Treatment: Drugs: Idasanutlin
Participants will self-administer idasanutlin tablets by mouth (PO) once daily (QD) for 5 days of each 28-day treatment cycle for up to 2 cycles of induction, up to 4 cycles of consolidation, and 12 cycles of maintenance, according to the study's protocol.
Treatment: Drugs: Cytarabine
Cytarabine will be administered for 7 days of each 28-day cycle for up to 2 cycles of induction treatment at a dose of 200 milligrams per meter squared (mg/m\^2) of body surface area, once daily (QD) by intravenous (IV) infusion. At the investigator's discretion, cytarabine will also be administered as part of chemotherapy consolidation at a dose of 1.5 g/m\^2 QD as IV infusion for 5 days of each 28-day cycle and for up to 4 cycles of treatment.
Treatment: Drugs: Daunorubicin
Daunorubicin will be administered for 3 days of each 28-day cycle for up to 2 cycles of induction treatment at a dose of 60 mg/m\^2 QD as IV infusion.
Treatment: Surgery: Allogeneic Hematopoietic Stem Cell Transplant (Allo-HSCT)
After induction treatment, participants who achieve remission will either receive chemotherapy consolidation treatment or undergo Allo-HSCT (as per local guidelines) at the investigator's discretion.
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Intervention code [1]
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Treatment: Drugs
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Intervention code [2]
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Treatment: Surgery
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Comparator / control treatment
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Control group
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Outcomes
Primary outcome [1]
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Dose Escalation Phase: Number of Participants With Dose-Limiting Toxicities (DLTs) During the First Cycle of Induction Treatment
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Assessment method [1]
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Sponsor's decision to prematurely terminate the study was made at the end of the Phase 1. The planned Phase 2 was not initiated. This decision was not based on safety concerns, but rather due to the overall company strategy about the adult AML
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Timepoint [1]
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Cycle 1 of induction treatment (1 cycle is 28 days)
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Primary outcome [2]
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Number of Participants With at Least One Adverse Event
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Assessment method [2]
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Sponsor's decision to prematurely terminate the study was made at the end of the Phase 1. The planned Phase 2 was not initiated. This decision was not based on safety concerns, but rather due to the overall company strategy about the adult AML.
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Timepoint [2]
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From Baseline until 28 days after the final dose of study drug (up to 2 years)
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Primary outcome [3]
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Number of Participants With Grade =3 Adverse Events, Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0)
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Assessment method [3]
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Sponsor's decision to prematurely terminate the study was made at the end of the Phase 1. The planned Phase 2 was not initiated. This decision was not based on safety concerns, but rather due to the overall company strategy about the adult AML
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Timepoint [3]
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From Baseline until 28 days after the final dose of study drug (up to 2 years)
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Primary outcome [4]
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Number of Participants Reporting Presence or Absence of Nausea Over Time, as Assessed Through Use of the National Cancer Institute (NCI) Patient-Reported Outcomes Common Terminology Criteria for Adverse Events (PRO-CTCAE)
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Assessment method [4]
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The sponsor decided not to continue the study based on the overall Company strategy in AML. Although data were collected, the small sample size and insufficient follow up rendered any analysis scientifically meaningless. As a consequence, no data were analyzed and this outcome measure was not conducted
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Timepoint [4]
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0
Day 1 of each treatment cycle (1 cycle is 28 days) and at study drug discontinuation (up to 2 years)
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Primary outcome [5]
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Change From Baseline Over Time in Reported Frequency of Nausea, as Assessed Through Use of the NCI PRO-CTCAE
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Assessment method [5]
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The sponsor decided not to continue the study based on the overall Company strategy in AML. Although data were collected, the small sample size and insufficient follow up rendered any analysis scientifically meaningless. As a consequence, no data were analyzed and this outcome measure was not conducted
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Timepoint [5]
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0
Baseline, Day 1 of each treatment cycle (1 cycle is 28 days), and at study drug discontinuation (up to 2 years)
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Primary outcome [6]
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Change From Baseline Over Time in Reported Severity of Nausea, as Assessed Through Use of the NCI PRO-CTCAE
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Assessment method [6]
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The sponsor decided not to continue the study based on the overall Company strategy in AML. Although data were collected, the small sample size and insufficient follow up rendered any analysis scientifically meaningless. As a consequence, no data were analyzed and this outcome measure was not conducted
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Timepoint [6]
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0
Baseline, Day 1 of each treatment cycle (1 cycle is 28 days), and at study drug discontinuation (up to 2 years)
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Primary outcome [7]
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Change From Baseline Over Time in Reported Degree of Interference With Daily Function Caused by Nausea, as Assessed Through Use of the NCI PRO-CTCAE
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Assessment method [7]
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The sponsor decided not to continue the study based on the overall Company strategy in AML. Although data were collected, the small sample size and insufficient follow up rendered any analysis scientifically meaningless. As a consequence, no data were analyzed and this outcome measure was not conducted
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Timepoint [7]
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0
Baseline, Day 1 of each treatment cycle (1 cycle is 28 days), and at study drug discontinuation (up to 2 years)
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Primary outcome [8]
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Change From Baseline Over Time in Overall Score for Nausea, as Assessed Through Use of the NCI PRO-CTCAE
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Assessment method [8]
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The sponsor decided not to continue the study based on the overall Company strategy in AML. Although data were collected, the small sample size and insufficient follow up rendered any analysis scientifically meaningless. As a consequence, no data were analyzed and this outcome measure was not conducted
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Timepoint [8]
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0
Baseline, Day 1 of each treatment cycle (1 cycle is 28 days), and at study drug discontinuation (up to 2 years)
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Primary outcome [9]
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Number of Participants Reporting Presence or Absence of Vomiting Over Time, as Assessed Through Use of the NCI PRO-CTCAE
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Assessment method [9]
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The sponsor decided not to continue the study based on the overall Company strategy in AML. Although data were collected, the small sample size and insufficient follow up rendered any analysis scientifically meaningless. As a consequence, no data were analyzed and this outcome measure was not conducted
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Timepoint [9]
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0
Day 1 of each treatment cycle (1 cycle is 28 days) and at study drug discontinuation (up to 2 years)
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Primary outcome [10]
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Change From Baseline Over Time in Reported Frequency of Vomiting, as Assessed Through Use of the NCI PRO-CTCAE
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Assessment method [10]
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The sponsor decided not to continue the study based on the overall Company strategy in AML. Although data were collected, the small sample size and insufficient follow up rendered any analysis scientifically meaningless. As a consequence, no data were analyzed and this outcome measure was not conducted
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Timepoint [10]
0
0
Baseline, Day 1 of each treatment cycle (1 cycle is 28 days), and at study drug discontinuation (up to 2 years)
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Primary outcome [11]
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Change From Baseline Over Time in Reported Severity of Vomiting, as Assessed Through Use of the NCI PRO-CTCAE
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Assessment method [11]
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0
The sponsor decided not to continue the study based on the overall Company strategy in AML. Although data were collected, the small sample size and insufficient follow up rendered any analysis scientifically meaningless. As a consequence, no data were analyzed and this outcome measure was not conducted
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Timepoint [11]
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0
Baseline, Day 1 of each treatment cycle (1 cycle is 28 days), and at study drug discontinuation (up to 2 years)
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Primary outcome [12]
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Change From Baseline Over Time in Reported Degree of Interference With Daily Function Caused by Vomiting, as Assessed Through Use of the NCI PRO-CTCAE
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Assessment method [12]
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0
The sponsor decided not to continue the study based on the overall Company strategy in AML. Although data were collected, the small sample size and insufficient follow up rendered any analysis scientifically meaningless. As a consequence, no data were analyzed and this outcome measure was not conducted
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Timepoint [12]
0
0
Baseline, Day 1 of each treatment cycle (1 cycle is 28 days), and at study drug discontinuation (up to 2 years)
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Primary outcome [13]
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0
Change From Baseline Over Time in Overall Score for Vomiting, as Assessed Through Use of the NCI PRO-CTCAE
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Assessment method [13]
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0
The sponsor decided not to continue the study based on the overall Company strategy in AML. Although data were collected, the small sample size and insufficient follow up rendered any analysis scientifically meaningless. As a consequence, no data were analyzed and this outcome measure was not conducted
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Timepoint [13]
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0
Baseline, Day 1 of each treatment cycle (1 cycle is 28 days), and at study drug discontinuation (up to 2 years)
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Primary outcome [14]
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Number of Participants Reporting Presence or Absence of Diarrhea Over Time, as Assessed Through Use of the NCI PRO-CTCAE Over Time
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Assessment method [14]
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0
The sponsor decided not to continue the study based on the overall Company strategy in AML. Although data were collected, the small sample size and insufficient follow up rendered any analysis scientifically meaningless. As a consequence, no data were analyzed and this outcome measure was not conducted
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Timepoint [14]
0
0
Day 1 of each treatment cycle (1 cycle is 28 days) and at study drug discontinuation (up to 2 years)
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Primary outcome [15]
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0
Change From Baseline in Reported Frequency of Diarrhea Over Time, as Assessed Through Use of the NCI PRO-CTCAE
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Assessment method [15]
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0
The sponsor decided not to continue the study based on the overall Company strategy in AML. Although data were collected, the small sample size and insufficient follow up rendered any analysis scientifically meaningless. As a consequence, no data were analyzed and this outcome measure was not conducted
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Timepoint [15]
0
0
Baseline, Day 1 of each treatment cycle (1 cycle is 28 days), and at study drug discontinuation (up to 2 years)
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Primary outcome [16]
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0
Change From Baseline in Reported Severity of Diarrhea Over Time, as Assessed Through Use of the NCI PRO-CTCAE
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Assessment method [16]
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0
The sponsor decided not to continue the study based on the overall Company strategy in AML. Although data were collected, the small sample size and insufficient follow up rendered any analysis scientifically meaningless. As a consequence, no data were analyzed and this outcome measure was not conducted
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Timepoint [16]
0
0
Baseline, Day 1 of each treatment cycle (1 cycle is 28 days), and at study drug discontinuation (up to 2 years)
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Primary outcome [17]
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0
Change From Baseline in Reported Degree of Interference With Daily Function Caused by Diarrhea Over Time, as Assessed Through Use of the NCI PRO-CTCAE
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Assessment method [17]
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0
The sponsor decided not to continue the study based on the overall Company strategy in AML. Although data were collected, the small sample size and insufficient follow up rendered any analysis scientifically meaningless. As a consequence, no data were analyzed and this outcome measure was not conducted
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Timepoint [17]
0
0
Baseline, Day 1 of each treatment cycle (1 cycle is 28 days), and at study drug discontinuation (up to 2 years)
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Primary outcome [18]
0
0
Change From Baseline in Overall Score for Diarrhea Over Time, as Assessed Through Use of the NCI PRO-CTCAE
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Assessment method [18]
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0
The sponsor decided not to continue the study based on the overall Company strategy in AML. Although data were collected, the small sample size and insufficient follow up rendered any analysis scientifically meaningless. As a consequence, no data were analyzed and this outcome measure was not conducted
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Timepoint [18]
0
0
Baseline, Day 1 of each treatment cycle (1 cycle is 28 days), and at study drug discontinuation (up to 2 years)
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Primary outcome [19]
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Number of Participants, Per ELN Categories, With a Complete Remission (CR) at the End of Induction Treatment, Among Those Treated at the Recommended Phase 2 Dose
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Assessment method [19]
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Sponsor's decision to prematurely terminate the study was made at the end of the Phase 1. This decision was not based on safety concerns, but rather due to the overall company strategy about the adult AML. Therefore this outcome measure was not conducted and no data available to report.
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Timepoint [19]
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At the end of induction treatment (up to 2 cycles; 1 cycle is 28 days)
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Secondary outcome [1]
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Dose Escalation and Expansion Phases: Percentage of Participants With a CR, Complete Remission With Incomplete Blood Count Recovery (CRi), or Complete Remission With Incomplete Platelet Count Recovery (CRp) at the End of Induction Treatment
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Assessment method [1]
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The sponsor decided not to continue the study based on the overall Company strategy in AML. Although data were collected, the small sample size and insufficient follow up rendered any analysis scientifically meaningless. As a consequence, no data were analyzed and this outcome measure was not conducted
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Timepoint [1]
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At the end of induction treatment (up to 2 cycles; 1 cycle is 28 days)
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Secondary outcome [2]
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Dose Escalation and Expansion Phases: Percentage of Participants With a CR or Complete Remission With Partial Hematologic Recovery (CRh) at the End of Induction Treatment
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Assessment method [2]
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0
Sponsor's decision to prematurely terminate the study was made at the end of the Phase 1. The planned Phase 2 was not initiated. This decision was not based on safety concerns, but rather due to the overall company strategy about the adult AML. Therefore this outcome measure was not conducted and no data available to report.
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Timepoint [2]
0
0
At the end of induction treatment (up to 2 cycles; 1 cycle is 28 days)
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Secondary outcome [3]
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Dose-Escalation and Expansion Phases: Percentage of Participants With a Negative Minimal Residual Disease (MRD) Status at the End of Induction Treatment
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Assessment method [3]
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0
Sponsor's decision to prematurely terminate the study was made at the end of the Phase 1. The planned Phase 2 was not initiated. This decision was not based on safety concerns, but rather due to the overall company strategy about the adult AML. Therefore this outcome measure was not conducted and no data available to report.
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Timepoint [3]
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0
At the end of induction treatment (up to 2 cycles; 1 cycle is 28 days)
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Secondary outcome [4]
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Post-Consolidation Phase: Percentage of Participants Converting From MRD-Positive to MRD-Negative Status at Any Time During Treatment
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Assessment method [4]
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The sponsor decided not to continue the study based on the overall Company strategy in AML. Although data were collected, the small sample size and insufficient follow up rendered any analysis scientifically meaningless. As a consequence, no data were analyzed and this outcome measure was not conducted
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Timepoint [4]
0
0
At the end of maintenance treatment (12 cycles, 1 cycle is 28 days)
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Secondary outcome [5]
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0
Kaplan-Meier Estimate of the Percentage of Participants in Event-Free Survival
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Assessment method [5]
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The sponsor decided not to continue the study based on the overall Company strategy in AML. Although data were collected, the small sample size and insufficient follow up rendered any analysis scientifically meaningless. As a consequence, no data were analyzed and this outcome measure was not conducted
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Timepoint [5]
0
0
Up to 5 years
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Secondary outcome [6]
0
0
Kaplan-Meier Estimate of the Percentage of Participants in Overall Survival
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Assessment method [6]
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0
The sponsor decided not to continue the study based on the overall Company strategy in AML. Although data were collected, the small sample size and insufficient follow up rendered any analysis scientifically meaningless. As a consequence, no data were analyzed and this outcome measure was not conducted
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Timepoint [6]
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0
Up to 5 years
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Secondary outcome [7]
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Kaplan-Meier Estimate of the Percentage of Participants in Relapse-Free Survival in Those Who Achieve Remission (CR, CRi, CRp, or CRh)
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Assessment method [7]
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The sponsor decided not to continue the study based on the overall Company strategy in AML. Although data were collected, the small sample size and insufficient follow up rendered any analysis scientifically meaningless. As a consequence, no data were analyzed and this outcome measure was not conducted
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Timepoint [7]
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0
Up to 5 years
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Secondary outcome [8]
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0
Change From Baseline Over Time in the Participant-Reported Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Questionnaire Total Score
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Assessment method [8]
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0
The sponsor decided not to continue the study based on the overall Company strategy in AML. Although data were collected, the small sample size and insufficient follow up rendered any analysis scientifically meaningless. As a consequence, no data were analyzed and this outcome measure was not conducted
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Timepoint [8]
0
0
Baseline, Day 1 of each cycle of induction and consolidation (1 cycle is 28 days), every 3 months starting at Cycle 1 of maintenance, and at study drug discontinuation (up to 2 years)
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Secondary outcome [9]
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0
Change From Baseline Over Time in Physical Function Scale Score of the Participant-Reported European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaire, Core 30 (EORTC QLQ-C30)
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Assessment method [9]
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0
The sponsor decided not to continue the study based on the overall Company strategy in AML. Although data were collected, the small sample size and insufficient follow up rendered any analysis scientifically meaningless. As a consequence, no data were analyzed and this outcome measure was not conducted
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Timepoint [9]
0
0
Baseline, Day 1 of first induction cycle only, Day 1 of each subsequent treatment cycle (1 cycle is 28 days), and at study drug discontinuation (up to 2 years)
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Secondary outcome [10]
0
0
Change From Baseline Over Time in Role Function Scale Score of the Participant-Reported EORTC QLQ-C30
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Assessment method [10]
0
0
The sponsor decided not to continue the study based on the overall Company strategy in AML. Although data were collected, the small sample size and insufficient follow up rendered any analysis scientifically meaningless. As a consequence, no data were analyzed and this outcome measure was not conducted
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Timepoint [10]
0
0
Baseline, Day 1 of first induction cycle only, Day 1 of each subsequent treatment cycle (1 cycle is 28 days), and at study drug discontinuation (up to 2 years)
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Secondary outcome [11]
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0
Change From Baseline Over Time in Global Health Status/Quality of Life Scale Score of the Participant-Reported EORTC QLQ-C30
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Assessment method [11]
0
0
The sponsor decided not to continue the study based on the overall Company strategy in AML. Although data were collected, the small sample size and insufficient follow up rendered any analysis scientifically meaningless. As a consequence, no data were analyzed and this outcome measure was not conducted
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Timepoint [11]
0
0
Baseline, Day 1 of first induction cycle only, Day 1 of each subsequent treatment cycle (1 cycle is 28 days), and at study drug discontinuation (up to 2 years)
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Secondary outcome [12]
0
0
Change From Baseline Over Time in Headache Symptom Score of the Participant-Reported European Organisation for Research and Treatment of Cancer (EORTC) Item Library Questionnaire
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Assessment method [12]
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0
The sponsor decided not to continue the study based on the overall Company strategy in AML. Although data were collected, the small sample size and insufficient follow up rendered any analysis scientifically meaningless. As a consequence, no data were analyzed and this outcome measure was not conducted
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Timepoint [12]
0
0
Baseline, Day 1 of each cycle of induction and consolidation (1 cycle is 28 days), every 3 months starting at Cycle 1 of maintenance, and at study drug discontinuation (up to 2 years)
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Secondary outcome [13]
0
0
Change From Baseline Over Time in Dizziness Symptom Score of the Participant-Reported EORTC Item Library Questionnaire
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Assessment method [13]
0
0
The Sponsor decided not to continue the study based on the overall Company strategy in AML. Due to the limited The sponsor decided not to continue the study based on the overall Company strategy in AML. Although data were collected, the small sample size and insufficient follow up rendered any analysis scientifically meaningless. As a consequence, no data were analyzed and this outcome measure was not conducted
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Timepoint [13]
0
0
Baseline, Day 1 of each cycle of induction and consolidation (1 cycle is 28 days), every 3 months starting at Cycle 1 of maintenance, and at study drug discontinuation (up to 2 years)
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Secondary outcome [14]
0
0
Change From Baseline Over Time in Bruising Symptom Score of the Participant-Reported EORTC Item Library Questionnaire
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Assessment method [14]
0
0
The sponsor decided not to continue the study based on the overall Company strategy in AML. Although data were collected, the small sample size and insufficient follow up rendered any analysis scientifically meaningless. As a consequence, no data were analyzed and this outcome measure was not conducted
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Timepoint [14]
0
0
Baseline, Day 1 of each cycle of induction and consolidation (1 cycle is 28 days), every 3 months starting at Cycle 1 of maintenance, and at study drug discontinuation (up to 2 years)
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Secondary outcome [15]
0
0
Change From Baseline Over Time in the European Quality of Life 5-Dimension, 5-Level Questionnaire (EQ-5D-5L) Index Utility Score
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Assessment method [15]
0
0
The sponsor decided not to continue the study based on the overall Company strategy in AML. Although data were collected, the small sample size and insufficient follow up rendered any analysis scientifically meaningless. As a consequence, no data were analyzed and this outcome measure was not conducted
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Timepoint [15]
0
0
Baseline, Day 1 of first induction cycle only, Day 1 of all cycles of consolidation (1 cycle is 28 days), every 3 months starting at Cycle 1 of maintenance, and at study drug discontinuation (up to 2 years)
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Secondary outcome [16]
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0
Change From Baseline Over Time in the EQ-5D-5L Visual Analogue Scale (VAS) Score
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Assessment method [16]
0
0
The sponsor decided not to continue the study based on the overall Company strategy in AML. Although data were collected, the small sample size and insufficient follow up rendered any analysis scientifically meaningless. As a consequence, no data were analyzed and this outcome measure was not conducted
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Timepoint [16]
0
0
Baseline, Day 1 of first induction cycle only, Day 1 of all cycles of consolidation (1 cycle is 28 days), every 3 months starting at Cycle 1 of maintenance, and at study drug discontinuation (up to 2 years)
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Secondary outcome [17]
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0
Area Under the Plasma Concentration-Time Curve (AUC) of Idasanutlin
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Assessment method [17]
0
0
The sponsor decided not to continue the study based on the overall Company strategy in AML. Although data were collected, the small sample size and insufficient follow up rendered any analysis scientifically meaningless. As a consequence, no data were analyzed and this outcome measure was not conducted
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Timepoint [17]
0
0
Pre-dose and at predefined intervals post-dose on Days 1, 3, and 5 of induction Cycle 1; Days 1 and 5 of consolidation Cycle 1; and Days 1 and 5 of maintenance Cycle 1 (1 cycle is 28 days)
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Secondary outcome [18]
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0
AUC of Cytarabine
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Assessment method [18]
0
0
The sponsor decided not to continue the study based on the overall Company strategy in AML. Although data were collected, the small sample size and insufficient follow up rendered any analysis scientifically meaningless. As a consequence, no data were analyzed and this outcome measure was not conducted
Query!
Timepoint [18]
0
0
Pre-dose and at predefined intervals post-dose on Days 1, 3, and 5 of induction Cycle 1; and Days 1 and 5 of consolidation Cycle 1 (1 cycle is 28 days)
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Secondary outcome [19]
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0
AUC of Daunorubicin
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Assessment method [19]
0
0
The sponsor decided not to continue the study based on the overall Company strategy in AML. Although data were collected, the small sample size and insufficient follow up rendered any analysis scientifically meaningless. As a consequence, no data were analyzed and this outcome measure was not conducted
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Timepoint [19]
0
0
Pre-dose and at predefined intervals post-dose on Days 1, 3, and 5 of induction Cycle 1 (1 cycle is 28 days)
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Secondary outcome [20]
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0
Maximum Observed Plasma Concentration (Cmax) of Idasanutlin
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Assessment method [20]
0
0
The sponsor decided not to continue the study based on the overall Company strategy in AML. Although data were collected, the small sample size and insufficient follow up rendered any analysis scientifically meaningless. As a consequence, no data were analyzed and this outcome measure was not conducted
Query!
Timepoint [20]
0
0
Pre-dose and at predefined intervals post-dose on Days 1, 3, and 5 of induction Cycle 1; Days 1 and 5 of consolidation Cycle 1; and Days 1 and 5 of maintenance Cycle 1 (1 cycle is 28 days)
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Secondary outcome [21]
0
0
Cmax of Cytarabine
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Assessment method [21]
0
0
The sponsor decided not to continue the study based on the overall Company strategy in AML. Although data were collected, the small sample size and insufficient follow up rendered any analysis scientifically meaningless. As a consequence, no data were analyzed and this outcome measure was not conducted
Query!
Timepoint [21]
0
0
Pre-dose and at predefined intervals post-dose on Days 1, 3, and 5 of induction Cycle 1; and Days 1 and 5 of consolidation Cycle 1 (1 cycle is 28 days)
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Secondary outcome [22]
0
0
Cmax of Daunorubicin
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Assessment method [22]
0
0
The sponsor decided not to continue the study based on the overall Company strategy in AML. Although data were collected, the small sample size and insufficient follow up rendered any analysis scientifically meaningless. As a consequence, no data were analyzed and this outcome measure was not conducted
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Timepoint [22]
0
0
Pre-dose and at predefined intervals post-dose on Days 1, 3, and 5 of induction Cycle 1 (1 cycle is 28 days)
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Secondary outcome [23]
0
0
Total Clearance (CL) of Idasanutlin
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Assessment method [23]
0
0
The sponsor decided not to continue the study based on the overall Company strategy in AML. Although data were collected, the small sample size and insufficient follow up rendered any analysis scientifically meaningless. As a consequence, no data were analyzed and this outcome measure was not conducted
Query!
Timepoint [23]
0
0
Pre-dose and at predefined intervals post-dose on Days 1, 3, and 5 of induction Cycle 1; Days 1 and 5 of consolidation Cycle 1; and Days 1 and 5 of maintenance Cycle 1 (1 cycle is 28 days)
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Secondary outcome [24]
0
0
CL of Cytarabine
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Assessment method [24]
0
0
The sponsor decided not to continue the study based on the overall Company strategy in AML. Although data were collected, the small sample size and insufficient follow up rendered any analysis scientifically meaningless. As a consequence, no data were analyzed and this outcome measure was not conducted
Query!
Timepoint [24]
0
0
Pre-dose and at predefined intervals post-dose on Days 1, 3, and 5 of induction Cycle 1; and Days 1 and 5 of consolidation Cycle 1 (1 cycle is 28 days)
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Secondary outcome [25]
0
0
CL of Daunorubicin
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Assessment method [25]
0
0
The sponsor decided not to continue the study based on the overall Company strategy in AML. Although data were collected, the small sample size and insufficient follow up rendered any analysis scientifically meaningless. As a consequence, no data were analyzed and this outcome measure was not conducted
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Timepoint [25]
0
0
Pre-dose and at predefined intervals post-dose on Days 1, 3, and 5 of induction Cycle 1 (1 cycle is 28 days)
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Secondary outcome [26]
0
0
Volume of Distribution at Steady State (Vss) of Idasanutlin
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Assessment method [26]
0
0
The sponsor decided not to continue the study based on the overall Company strategy in AML. Although data were collected, the small sample size and insufficient follow up rendered any analysis scientifically meaningless. As a consequence, no data were analyzed and this outcome measure was not conducted
Query!
Timepoint [26]
0
0
Pre-dose and at predefined intervals post-dose on Days 1, 3, and 5 of induction Cycle 1; Days 1 and 5 of consolidation Cycle 1; and Days 1 and 5 of maintenance Cycle 1 (1 cycle is 28 days)
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Secondary outcome [27]
0
0
Vss of Cytarabine
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Assessment method [27]
0
0
The sponsor decided not to continue the study based on the overall Company strategy in AML. Although data were collected, the small sample size and insufficient follow up rendered any analysis scientifically meaningless. As a consequence, no data were analyzed and this outcome measure was not conducted
Query!
Timepoint [27]
0
0
Pre-dose and at predefined intervals post-dose on Days 1, 3, and 5 of induction Cycle 1; and Days 1 and 5 of consolidation Cycle 1 (1 cycle is 28 days)
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Secondary outcome [28]
0
0
Vss of Daunorubicin
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Assessment method [28]
0
0
The sponsor decided not to continue the study based on the overall Company strategy in AML. Although data were collected, the small sample size and insufficient follow up rendered any analysis scientifically meaningless. As a consequence, no data were analyzed and this outcome measure was not conducted
Query!
Timepoint [28]
0
0
Pre-dose and at predefined intervals post-dose on Days 1, 3, and 5 of induction Cycle 1 (1 cycle is 28 days)
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Secondary outcome [29]
0
0
Terminal Half-Life (t1/2) of Idasanutlin
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Assessment method [29]
0
0
The sponsor decided not to continue the study based on the overall Company strategy in AML. Although data were collected, the small sample size and insufficient follow up rendered any analysis scientifically meaningless. As a consequence, no data were analyzed and this outcome measure was not conducted
Query!
Timepoint [29]
0
0
Pre-dose and at predefined intervals post-dose on Days 1, 3, and 5 of induction Cycle 1; Days 1 and 5 of consolidation Cycle 1; and Days 1 and 5 of maintenance Cycle 1 (1 cycle is 28 days)
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Secondary outcome [30]
0
0
t1/2 of Cytarabine
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Assessment method [30]
0
0
The sponsor decided not to continue the study based on the overall Company strategy in AML. Although data were collected, the small sample size and insufficient follow up rendered any analysis scientifically meaningless. As a consequence, no data were analyzed and this outcome measure was not conducted
Query!
Timepoint [30]
0
0
Pre-dose and at predefined intervals post-dose on Days 1, 3, and 5 of induction Cycle 1; and Days 1 and 5 of consolidation Cycle 1 (1 cycle is 28 days)
Query!
Secondary outcome [31]
0
0
t1/2 of Daunorubicin
Query!
Assessment method [31]
0
0
The sponsor decided not to continue the study based on the overall Company strategy in AML. Although data were collected, the small sample size and insufficient follow up rendered any analysis scientifically meaningless. As a consequence, no data were analyzed and this outcome measure was not conducted
Query!
Timepoint [31]
0
0
Pre-dose and at predefined intervals post-dose on Days 1, 3, and 5 of induction Cycle 1 (1 cycle is 28 days)
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Eligibility
Key inclusion criteria
Inclusion Criteria for All Study Phases:
* Eastern Cooperative Oncology Group (ECOG) performance status =2
* Adequate hepatic and renal function
* For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating eggs with a failure rate of <1% per year during the treatment period and for at least 6 months after the final dose of idasanutlin, cytarabine, or daunorubicin. Women must refrain from donating eggs during this same period.
* For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive, measures, and agreement to refrain from donating sperm that together result in a failure rate of <1% per year during the treatment period and for 6 months after the final dose of idasanutlin, cytarabine, or daunorubicin. Men must refrain from donating sperm during this same period.
Inclusion Criteria for Patients in the Dose-Escalation and Expansion Phases:
- Documented/confirmed newly diagnosed acute myeloid leukemia (AML) not previously treated according to World Health Organization (WHO)
Inclusion Criteria for Patients in the Post-Consolidation Phase:
- Documented/confirmed AML according to WHO in remission after induction, within 21 days of end of last chemotherapy consolidation cycle, and were minimum residual disease (MRD) positive at the end of induction as per local laboratory assessment
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Minimum age
18
Years
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Maximum age
No limit
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Sex
Both males and females
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Can healthy volunteers participate?
No
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Key exclusion criteria
Exclusion Criteria for All Study Phases:
* Clinical evidence of central nervous system (CNS) leukemia
* Any Grade =2 non-hematologic toxicities prior to starting therapy
* Current treatment with any other investigational or commercial agents or therapies administered with the intention to treat their malignancy with the exception of hydroxyurea (HU) or 6-mercaptopurine (6-MP)
* Treatment-related AML
* Acute promyelocytic leukemia
* History of other malignancy that could affect compliance with the protocol or interpretation of results
* Any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study, impair the ability of the investigator to evaluate the patient, or impair the patient's ability to complete the study
* Echocardiogram (ECHO) or multiple-gated acquisition (MUGA) scan showing ejection fraction =40%
* Non-malignant medical illnesses that are uncontrolled or whose control may be jeopardized by this study treatment, such as hereditary coagulation disorders, insulin-dependent diabetes mellitus not optimally controlled with medical management (e.g., presence of ketoacidosis), or active GI conditions affecting absorption
* Infection considered by the investigator to be clinically uncontrolled or of unacceptable risk to the patient upon the induction of neutropenia, that is, patients who are or should be on antimicrobial agents for the treatment of active infection
* Febrile patients within 72 hours of study treatment initiation
* Patients with a history of active or chronic infectious hepatitis unless serology demonstrates clearance of infection
* Patients who are unable to interrupt treatment with moderate to strong CYP2C8 inducers and inhibitors
* Patients who are unable to temporarily interrupt treatment with oral or parenteral anticoagulants/anti-platelet agents during treatment phase
* Patients who have a history of clinically significant liver cirrhosis
* Patients with extramedullary AML with no evidence of systemic involvement
* Pregnant or breastfeeding patients
* Known history of HIV-positive status
* Patients who might refuse to receive blood products and/or have a hypersensitivity to blood products
* Prior treatment with an MDM2 antagonist
* Patients with clinically relevant QTc prolongation, a family history of long QT syndrome
Exclusion Criteria for Patients in the Phase Ib Dose-Escalation Phase:
- Adverse risk patients as per European LeukemiaNet (ELN) 2017 criteria
Exclusion Criteria for Patients in Phase Ib Post-Consolidation Phase:
* Any ongoing Grade =2 hematologic adverse events prior to starting therapy
* Previous hematopoietic stem cell transplant (HSCT)
Exclusion Criteria for Patients in the Dose-Escalation Phase and Patients in the Favorable/Intermediate-Risk Cohort of the Expansion Phase:
- Secondary AML, defined as AML evolving from antecedent hematologic disorder (AHD)
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Study design
Purpose of the study
Treatment
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Allocation to intervention
Non-randomised trial
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Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
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Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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Masking / blinding
Open (masking not used)
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Who is / are masked / blinded?
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Intervention assignment
Other
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Other design features
Query!
Phase
Phase 1
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Type of endpoint/s
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Statistical methods / analysis
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Recruitment
Recruitment status
Stopped early
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Data analysis
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Reason for early stopping/withdrawal
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Other reasons
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Date of first participant enrolment
Anticipated
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Actual
25/03/2019
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Date of last participant enrolment
Anticipated
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Actual
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Date of last data collection
Anticipated
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Actual
10/09/2020
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Sample size
Target
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Accrual to date
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Final
24
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Recruitment in Australia
Recruitment state(s)
VIC,WA
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Recruitment hospital [1]
0
0
The Alfred Hospital - Prahan
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Recruitment hospital [2]
0
0
Royal Perth Hospital - Perth
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Recruitment postcode(s) [1]
0
0
3181 - Prahan
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Recruitment postcode(s) [2]
0
0
6000 - Perth
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Recruitment outside Australia
Country [1]
0
0
United States of America
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State/province [1]
0
0
California
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Country [2]
0
0
United States of America
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State/province [2]
0
0
Colorado
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Country [3]
0
0
United States of America
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State/province [3]
0
0
Illinois
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Country [4]
0
0
United States of America
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State/province [4]
0
0
Iowa
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Country [5]
0
0
United States of America
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State/province [5]
0
0
Kansas
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Country [6]
0
0
United States of America
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State/province [6]
0
0
Massachusetts
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Country [7]
0
0
United States of America
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State/province [7]
0
0
New York
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Country [8]
0
0
United States of America
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State/province [8]
0
0
North Carolina
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Country [9]
0
0
United States of America
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State/province [9]
0
0
Ohio
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Country [10]
0
0
United States of America
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State/province [10]
0
0
Pennsylvania
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Country [11]
0
0
United States of America
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State/province [11]
0
0
Texas
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Country [12]
0
0
France
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State/province [12]
0
0
Lyon
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Country [13]
0
0
France
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State/province [13]
0
0
Marseille
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Country [14]
0
0
France
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State/province [14]
0
0
Nantes
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Country [15]
0
0
France
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State/province [15]
0
0
Paris
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Country [16]
0
0
France
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State/province [16]
0
0
Toulouse
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Country [17]
0
0
Italy
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State/province [17]
0
0
Emilia-Romagna
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Country [18]
0
0
Italy
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State/province [18]
0
0
Lombardia
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Country [19]
0
0
Spain
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State/province [19]
0
0
Barcelona
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Country [20]
0
0
Spain
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State/province [20]
0
0
Madrid
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Country [21]
0
0
Spain
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State/province [21]
0
0
Sevilla
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Country [22]
0
0
Spain
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State/province [22]
0
0
Valencia
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Funding & Sponsors
Primary sponsor type
Commercial sector/industry
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Name
Hoffmann-La Roche
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Address
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Country
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Ethics approval
Ethics application status
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Summary
Brief summary
This Phase Ib/II, open-label, multicenter, non-randomized study will evaluate the safety, efficacy, and pharmacokinetics of idasanutlin when it is given in combination with cytarabine and daunorubicin in induction, in combination with cytarabine in consolidation, and as a single agent in maintenance for treating participants with acute myeloid leukemia (AML).
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Trial website
https://clinicaltrials.gov/study/NCT03850535
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Trial related presentations / publications
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Public notes
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Contacts
Principal investigator
Name
0
0
Clinical Trials
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Address
0
0
Hoffmann-La Roche
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Country
0
0
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Phone
0
0
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Fax
0
0
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Email
0
0
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Contact person for public queries
Name
0
0
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Address
0
0
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Country
0
0
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Phone
0
0
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Fax
0
0
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Email
0
0
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Contact person for scientific queries
Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
Query!
No/undecided IPD sharing reason/comment
Qualified researchers may request access to individual patient level data through the request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/).
For further details on Roche's Global Policy on Sharing of Clinical Study Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).
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What supporting documents are/will be available?
No Supporting Document Provided
Type
Other Details
Attachment
Study protocol
Study Protocol and Statistical Analysis Plan
https://cdn.clinicaltrials.gov/large-docs/35/NCT03850535/Prot_SAP_000.pdf
Statistical analysis plan
Study Protocol and Statistical Analysis Plan
https://cdn.clinicaltrials.gov/large-docs/35/NCT03850535/Prot_SAP_000.pdf
Results publications and other study-related documents
No documents have been uploaded by study researchers.
Results not provided in
https://clinicaltrials.gov/study/NCT03850535