Acute Myeloid Leukemia
Conditions
Keywords
AML
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).
Interventions
DRUGIdasanutlin
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.
DRUGCytarabine
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.
DRUGDaunorubicin
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.
PROCEDUREAllogeneic 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.
Sponsors
Hoffmann-La Roche
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dose Escalation Phase: Number of Participants With Dose-Limiting Toxicities (DLTs) During the First Cycle of Induction Treatment | Cycle 1 of induction treatment (1 cycle is 28 days) | 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 |
| Number of Participants With at Least One Adverse Event | From Baseline until 28 days after the final dose of study drug (up to 2 years) | 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. |
| 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) | From Baseline until 28 days after the final dose of study drug (up to 2 years) | 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 |
| 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) | Day 1 of each treatment cycle (1 cycle is 28 days) and at study drug discontinuation (up to 2 years) | 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 |
| Change From Baseline Over Time in Reported Frequency of Nausea, as Assessed Through Use of the NCI PRO-CTCAE | Baseline, Day 1 of each treatment cycle (1 cycle is 28 days), and at study drug discontinuation (up to 2 years) | 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 |
| Change From Baseline Over Time in Reported Severity of Nausea, as Assessed Through Use of the NCI PRO-CTCAE | Baseline, Day 1 of each treatment cycle (1 cycle is 28 days), and at study drug discontinuation (up to 2 years) | 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 |
| 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 | Baseline, Day 1 of each treatment cycle (1 cycle is 28 days), and at study drug discontinuation (up to 2 years) | 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 |
| Change From Baseline Over Time in Overall Score for Nausea, as Assessed Through Use of the NCI PRO-CTCAE | Baseline, Day 1 of each treatment cycle (1 cycle is 28 days), and at study drug discontinuation (up to 2 years) | 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 |
| Number of Participants Reporting Presence or Absence of Vomiting Over Time, as Assessed Through Use of the NCI PRO-CTCAE | Day 1 of each treatment cycle (1 cycle is 28 days) and at study drug discontinuation (up to 2 years) | 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 |
| Change From Baseline Over Time in Reported Frequency of Vomiting, as Assessed Through Use of the NCI PRO-CTCAE | Baseline, Day 1 of each treatment cycle (1 cycle is 28 days), and at study drug discontinuation (up to 2 years) | 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 |
| Change From Baseline Over Time in Reported Severity of Vomiting, as Assessed Through Use of the NCI PRO-CTCAE | Baseline, Day 1 of each treatment cycle (1 cycle is 28 days), and at study drug discontinuation (up to 2 years) | 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 |
| 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 | Baseline, Day 1 of each treatment cycle (1 cycle is 28 days), and at study drug discontinuation (up to 2 years) | 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 |
| Change From Baseline Over Time in Overall Score for Vomiting, as Assessed Through Use of the NCI PRO-CTCAE | Baseline, Day 1 of each treatment cycle (1 cycle is 28 days), and at study drug discontinuation (up to 2 years) | 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 |
| Number of Participants Reporting Presence or Absence of Diarrhea Over Time, as Assessed Through Use of the NCI PRO-CTCAE Over Time | Day 1 of each treatment cycle (1 cycle is 28 days) and at study drug discontinuation (up to 2 years) | 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 |
| Change From Baseline in Reported Frequency of Diarrhea Over Time, as Assessed Through Use of the NCI PRO-CTCAE | Baseline, Day 1 of each treatment cycle (1 cycle is 28 days), and at study drug discontinuation (up to 2 years) | 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 |
| Change From Baseline in Reported Severity of Diarrhea Over Time, as Assessed Through Use of the NCI PRO-CTCAE | Baseline, Day 1 of each treatment cycle (1 cycle is 28 days), and at study drug discontinuation (up to 2 years) | 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 |
| 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 | Baseline, Day 1 of each treatment cycle (1 cycle is 28 days), and at study drug discontinuation (up to 2 years) | 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 |
| Change From Baseline in Overall Score for Diarrhea Over Time, as Assessed Through Use of the NCI PRO-CTCAE | Baseline, Day 1 of each treatment cycle (1 cycle is 28 days), and at study drug discontinuation (up to 2 years) | 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 |
| 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 | At the end of induction treatment (up to 2 cycles; 1 cycle is 28 days) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | At the end of induction treatment (up to 2 cycles; 1 cycle is 28 days) | 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 |
| 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 | At the end of induction treatment (up to 2 cycles; 1 cycle is 28 days) | 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. |
| Dose-Escalation and Expansion Phases: Percentage of Participants With a Negative Minimal Residual Disease (MRD) Status at the End of Induction Treatment | At the end of induction treatment (up to 2 cycles; 1 cycle is 28 days) | 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. |
| Post-Consolidation Phase: Percentage of Participants Converting From MRD-Positive to MRD-Negative Status at Any Time During Treatment | At the end of maintenance treatment (12 cycles, 1 cycle is 28 days) | 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 |
| Kaplan-Meier Estimate of the Percentage of Participants in Event-Free Survival | Up to 5 years | 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 |
| Kaplan-Meier Estimate of the Percentage of Participants in Overall Survival | Up to 5 years | 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 |
| Kaplan-Meier Estimate of the Percentage of Participants in Relapse-Free Survival in Those Who Achieve Remission (CR, CRi, CRp, or CRh) | Up to 5 years | 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 |
| Change From Baseline Over Time in the Participant-Reported Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Questionnaire Total Score | 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) | 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 |
| 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) | 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) | 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 |
| Change From Baseline Over Time in Role Function Scale Score of the Participant-Reported EORTC QLQ-C30 | 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) | 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 |
| Change From Baseline Over Time in Global Health Status/Quality of Life Scale Score of the Participant-Reported EORTC QLQ-C30 | 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) | 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 |
| 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 | 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) | 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 |
| Change From Baseline Over Time in Dizziness Symptom Score of the Participant-Reported EORTC Item Library Questionnaire | 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) | 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 |
| Change From Baseline Over Time in Bruising Symptom Score of the Participant-Reported EORTC Item Library Questionnaire | 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) | 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 |
| Change From Baseline Over Time in the European Quality of Life 5-Dimension, 5-Level Questionnaire (EQ-5D-5L) Index Utility Score | 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) | 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 |
| Change From Baseline Over Time in the EQ-5D-5L Visual Analogue Scale (VAS) Score | 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) | 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 |
| Area Under the Plasma Concentration-Time Curve (AUC) of Idasanutlin | 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) | 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 |
| AUC of Cytarabine | 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) | 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 |
| AUC of Daunorubicin | Pre-dose and at predefined intervals post-dose on Days 1, 3, and 5 of induction Cycle 1 (1 cycle is 28 days) | 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 |
| Maximum Observed Plasma Concentration (Cmax) of Idasanutlin | 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) | 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 |
| Cmax of Cytarabine | 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) | 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 |
| Cmax of Daunorubicin | Pre-dose and at predefined intervals post-dose on Days 1, 3, and 5 of induction Cycle 1 (1 cycle is 28 days) | 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 |
| Total Clearance (CL) of Idasanutlin | 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) | 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 |
| CL of Cytarabine | 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) | 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 |
| CL of Daunorubicin | Pre-dose and at predefined intervals post-dose on Days 1, 3, and 5 of induction Cycle 1 (1 cycle is 28 days) | 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 |
| Volume of Distribution at Steady State (Vss) of Idasanutlin | 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) | 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 |
| Vss of Cytarabine | 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) | 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 |
| Vss of Daunorubicin | Pre-dose and at predefined intervals post-dose on Days 1, 3, and 5 of induction Cycle 1 (1 cycle is 28 days) | 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 |
| Terminal Half-Life (t1/2) of Idasanutlin | 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) | 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 |
| t1/2 of Cytarabine | 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) | 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 |
| t1/2 of Daunorubicin | Pre-dose and at predefined intervals post-dose on Days 1, 3, and 5 of induction Cycle 1 (1 cycle is 28 days) | 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 |
Countries
Australia, France, Italy, Spain, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Dose-Escalation Cohort 1 200 mg idasanutlin day 1 to day 5 in combination with cytarabine 200mg day 1 to day 7 and daunorubicin 60mg day 1 to day 3 in induction | 4 |
| Dose Escalation Cohort 2 350 mg idasanutlin day 1 to day 5 in combination with cytarabine 200mg day 1 to day 7 and daunorubicin 60mg day 1 to day 3 in induction | 9 |
| Dose Escalation Cohort 3 250 mg idasanutlin day 1 to day 5 in combination with cytarabine 200mg day 1 to day 7 and daunorubicin 60mg day 1 to day 3 in induction | 6 |
| Post Consolidation Cohort 150 mg idasanultin day 1 to 5 in maintenance of first remission | 4 |
| Total | 23 |
Baseline characteristics
| Characteristic | Dose-Escalation Cohort 1 | Dose Escalation Cohort 2 | Dose Escalation Cohort 3 | Post Consolidation Cohort | Total |
|---|---|---|---|---|---|
| Age, Continuous | 49.5 Years STANDARD_DEVIATION 17.1 | 45.2 Years STANDARD_DEVIATION 16.9 | 49.8 Years STANDARD_DEVIATION 14 | 64.8 Years STANDARD_DEVIATION 7.2 | 50.6 Years STANDARD_DEVIATION 15.6 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 0 Participants | 5 Participants | 0 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 2 Participants | 9 Participants | 0 Participants | 3 Participants | 14 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 2 Participants | 1 Participants | 5 Participants |
| Race (NIH/OMB) White | 3 Participants | 7 Participants | 4 Participants | 3 Participants | 17 Participants |
| Sex: Female, Male Female | 2 Participants | 3 Participants | 3 Participants | 3 Participants | 11 Participants |
| Sex: Female, Male Male | 2 Participants | 6 Participants | 3 Participants | 1 Participants | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 2 / 4 | 1 / 9 | 0 / 6 | 1 / 4 |
| other Total, other adverse events | 4 / 4 | 9 / 9 | 6 / 6 | 4 / 4 |
| serious Total, serious adverse events | 3 / 4 | 4 / 9 | 2 / 6 | 1 / 4 |
Outcome results
Primary
Change From Baseline in Overall Score for Diarrhea Over Time, as Assessed Through Use of the NCI PRO-CTCAE
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
Time frame: Baseline, Day 1 of each treatment cycle (1 cycle is 28 days), and at study drug discontinuation (up to 2 years)
Population: Due to the insufficient enrollment of the planned Analysis Population, the planned outcome measurements were not conducted and result data were not collected.
Primary
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
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
Time frame: Baseline, Day 1 of each treatment cycle (1 cycle is 28 days), and at study drug discontinuation (up to 2 years)
Population: Due to the insufficient enrollment of the planned Analysis Population, the planned outcome measurements were not conducted and result data were not collected.
Primary
Change From Baseline in Reported Frequency of Diarrhea Over Time, as Assessed Through Use of the NCI PRO-CTCAE
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
Time frame: Baseline, Day 1 of each treatment cycle (1 cycle is 28 days), and at study drug discontinuation (up to 2 years)
Population: Due to the insufficient enrollment of the planned Analysis Population, the planned outcome measurements were not conducted and result data were not collected.
Primary
Change From Baseline in Reported Severity of Diarrhea Over Time, as Assessed Through Use of the NCI PRO-CTCAE
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
Time frame: Baseline, Day 1 of each treatment cycle (1 cycle is 28 days), and at study drug discontinuation (up to 2 years)
Population: Due to the insufficient enrollment of the planned Analysis Population, the planned outcome measurements were not conducted and result data were not collected.
Primary
Change From Baseline Over Time in Overall Score for Nausea, as Assessed Through Use of the NCI PRO-CTCAE
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
Time frame: Baseline, Day 1 of each treatment cycle (1 cycle is 28 days), and at study drug discontinuation (up to 2 years)
Population: Due to the insufficient enrollment of the planned Analysis Population, the planned outcome measurements were not conducted and result data were not collected.
Primary
Change From Baseline Over Time in Overall Score for Vomiting, as Assessed Through Use of the NCI PRO-CTCAE
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
Time frame: Baseline, Day 1 of each treatment cycle (1 cycle is 28 days), and at study drug discontinuation (up to 2 years)
Population: Due to the insufficient enrollment of the planned Analysis Population, the planned outcome measurements were not conducted and result data were not collected.
Primary
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
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
Time frame: Baseline, Day 1 of each treatment cycle (1 cycle is 28 days), and at study drug discontinuation (up to 2 years)
Population: Due to the insufficient enrollment of the planned Analysis Population, the planned outcome measurements were not conducted and result data were not collected.
Primary
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
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
Time frame: Baseline, Day 1 of each treatment cycle (1 cycle is 28 days), and at study drug discontinuation (up to 2 years)
Population: Due to the insufficient enrollment of the planned Analysis Population, the planned outcome measurements were not conducted and result data were not collected.
Primary
Change From Baseline Over Time in Reported Frequency of Nausea, as Assessed Through Use of the NCI PRO-CTCAE
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
Time frame: Baseline, Day 1 of each treatment cycle (1 cycle is 28 days), and at study drug discontinuation (up to 2 years)
Population: Due to the insufficient enrollment of the planned Analysis Population, the planned outcome measurements were not conducted and result data were not collected.
Primary
Change From Baseline Over Time in Reported Frequency of Vomiting, as Assessed Through Use of the NCI PRO-CTCAE
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
Time frame: Baseline, Day 1 of each treatment cycle (1 cycle is 28 days), and at study drug discontinuation (up to 2 years)
Population: Due to the insufficient enrollment of the planned Analysis Population, the planned outcome measurements were not conducted and result data were not collected.
Primary
Change From Baseline Over Time in Reported Severity of Nausea, as Assessed Through Use of the NCI PRO-CTCAE
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
Time frame: Baseline, Day 1 of each treatment cycle (1 cycle is 28 days), and at study drug discontinuation (up to 2 years)
Population: Due to the insufficient enrollment of the planned Analysis Population, the planned outcome measurements were not conducted and result data were not collected.
Primary
Change From Baseline Over Time in Reported Severity of Vomiting, as Assessed Through Use of the NCI PRO-CTCAE
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
Time frame: Baseline, Day 1 of each treatment cycle (1 cycle is 28 days), and at study drug discontinuation (up to 2 years)
Population: Due to the insufficient enrollment of the planned Analysis Population, the planned outcome measurements were not conducted and result data were not collected.
Primary
Dose Escalation Phase: Number of Participants With Dose-Limiting Toxicities (DLTs) During the First Cycle of Induction Treatment
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
Time frame: Cycle 1 of induction treatment (1 cycle is 28 days)
Population: ITT Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dose-Escalation Cohort 1 | Dose Escalation Phase: Number of Participants With Dose-Limiting Toxicities (DLTs) During the First Cycle of Induction Treatment | 2 Participants |
| Dose Escalation Cohort 2 | Dose Escalation Phase: Number of Participants With Dose-Limiting Toxicities (DLTs) During the First Cycle of Induction Treatment | 4 Participants |
| Dose Escalation Cohort 3 | Dose Escalation Phase: Number of Participants With Dose-Limiting Toxicities (DLTs) During the First Cycle of Induction Treatment | 0 Participants |
| Post Consolidation Cohort | Dose Escalation Phase: Number of Participants With Dose-Limiting Toxicities (DLTs) During the First Cycle of Induction Treatment | 0 Participants |
Primary
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
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.
Time frame: At the end of induction treatment (up to 2 cycles; 1 cycle is 28 days)
Population: Due to the insufficient enrollment of the planned Analysis Population, the planned outcome measurements were not conducted and result data were not collected.
| Arm | Measure | Group | Value |
|---|---|---|---|
| Unknown | 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 | ELN Classification: Adverse | — |
| Unknown | 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 | ELN Classification: Favorable | — |
| Unknown | 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 | ELN Classification: Intermediate | — |
Primary
Number of Participants Reporting Presence or Absence of Diarrhea Over Time, as Assessed Through Use of the NCI PRO-CTCAE Over Time
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
Time frame: Day 1 of each treatment cycle (1 cycle is 28 days) and at study drug discontinuation (up to 2 years)
Population: Due to the insufficient enrollment of the planned Analysis Population, the planned outcome measurements were not conducted and result data were not collected.
Primary
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)
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
Time frame: Day 1 of each treatment cycle (1 cycle is 28 days) and at study drug discontinuation (up to 2 years)
Population: Due to the insufficient enrollment of the planned Analysis Population, the planned outcome measurements were not conducted and result data were not collected.
Primary
Number of Participants Reporting Presence or Absence of Vomiting Over Time, as Assessed Through Use of the NCI PRO-CTCAE
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
Time frame: Day 1 of each treatment cycle (1 cycle is 28 days) and at study drug discontinuation (up to 2 years)
Population: Due to the insufficient enrollment of the planned Analysis Population, the planned outcome measurements were not conducted and result data were not collected.
Primary
Number of Participants With at Least One Adverse Event
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.
Time frame: From Baseline until 28 days after the final dose of study drug (up to 2 years)
Population: Safety Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dose-Escalation Cohort 1 | Number of Participants With at Least One Adverse Event | 4 Percentage of Participants |
| Dose Escalation Cohort 2 | Number of Participants With at Least One Adverse Event | 9 Percentage of Participants |
| Dose Escalation Cohort 3 | Number of Participants With at Least One Adverse Event | 6 Percentage of Participants |
| Post Consolidation Cohort | Number of Participants With at Least One Adverse Event | 4 Percentage of Participants |
Primary
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)
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
Time frame: From Baseline until 28 days after the final dose of study drug (up to 2 years)
Population: Safety Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dose-Escalation Cohort 1 | 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) | 4 Participants |
| Dose Escalation Cohort 2 | 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) | 9 Participants |
| Dose Escalation Cohort 3 | 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) | 5 Participants |
| Post Consolidation Cohort | 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) | 4 Participants |
Secondary
Area Under the Plasma Concentration-Time Curve (AUC) of Idasanutlin
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
Time frame: 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)
Population: Due to the insufficient enrollment of the planned Analysis Population, the planned outcome measurements were not conducted and result data were not collected.
Secondary
AUC of Cytarabine
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
Time frame: 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)
Population: Due to the insufficient enrollment of the planned Analysis Population, the planned outcome measurements were not conducted and result data were not collected.
Secondary
AUC of Daunorubicin
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
Time frame: Pre-dose and at predefined intervals post-dose on Days 1, 3, and 5 of induction Cycle 1 (1 cycle is 28 days)
Population: Due to the insufficient enrollment of the planned Analysis Population, the planned outcome measurements were not conducted and result data were not collected.
Secondary
Change From Baseline Over Time in Bruising Symptom Score of the Participant-Reported EORTC Item Library Questionnaire
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
Time frame: 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)
Population: Due to the insufficient enrollment of the planned Analysis Population, the planned outcome measurements were not conducted and result data were not collected.
Secondary
Change From Baseline Over Time in Dizziness Symptom Score of the Participant-Reported EORTC Item Library Questionnaire
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
Time frame: 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)
Population: Due to the insufficient enrollment of the planned Analysis Population, the planned outcome measurements were not conducted and result data were not collected.
Secondary
Change From Baseline Over Time in Global Health Status/Quality of Life Scale Score of the Participant-Reported EORTC QLQ-C30
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
Time frame: 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)
Population: Due to the insufficient enrollment of the planned Analysis Population, the planned outcome measurements were not conducted and result data were not collected.
Secondary
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
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
Time frame: 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)
Population: Due to the insufficient enrollment of the planned Analysis Population, the planned outcome measurements were not conducted and result data were not collected.
Secondary
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)
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
Time frame: 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)
Population: Due to the insufficient enrollment of the planned Analysis Population, the planned outcome measurements were not conducted and result data were not collected.
Secondary
Change From Baseline Over Time in Role Function Scale Score of the Participant-Reported EORTC QLQ-C30
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
Time frame: 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)
Population: Due to the insufficient enrollment of the planned Analysis Population, the planned outcome measurements were not conducted and result data were not collected.
Secondary
Change From Baseline Over Time in the EQ-5D-5L Visual Analogue Scale (VAS) Score
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
Time frame: 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)
Population: Due to the insufficient enrollment of the planned Analysis Population, the planned outcome measurements were not conducted and result data were not collected.
Secondary
Change From Baseline Over Time in the European Quality of Life 5-Dimension, 5-Level Questionnaire (EQ-5D-5L) Index Utility Score
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
Time frame: 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)
Population: Due to the insufficient enrollment of the planned Analysis Population, the planned outcome measurements were not conducted and result data were not collected.
Secondary
Change From Baseline Over Time in the Participant-Reported Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Questionnaire Total Score
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
Time frame: 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)
Population: Due to the insufficient enrollment of the planned Analysis Population, the planned outcome measurements were not conducted and result data were not collected.
Secondary
CL of Cytarabine
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
Time frame: 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)
Population: Due to the insufficient enrollment of the planned Analysis Population, the planned outcome measurements were not conducted and result data were not collected.
Secondary
CL of Daunorubicin
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
Time frame: Pre-dose and at predefined intervals post-dose on Days 1, 3, and 5 of induction Cycle 1 (1 cycle is 28 days)
Population: Due to the insufficient enrollment of the planned Analysis Population, the planned outcome measurements were not conducted and result data were not collected.
Secondary
Cmax of Cytarabine
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
Time frame: 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)
Population: Due to the insufficient enrollment of the planned Analysis Population, the planned outcome measurements were not conducted and result data were not collected.
Secondary
Cmax of Daunorubicin
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
Time frame: Pre-dose and at predefined intervals post-dose on Days 1, 3, and 5 of induction Cycle 1 (1 cycle is 28 days)
Population: Due to the insufficient enrollment of the planned Analysis Population, the planned outcome measurements were not conducted and result data were not collected.
Secondary
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
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
Time frame: At the end of induction treatment (up to 2 cycles; 1 cycle is 28 days)
Population: Due to the insufficient enrollment of the planned Analysis Population, the planned outcome measurements were not conducted and result data were not collected.
Secondary
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
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.
Time frame: At the end of induction treatment (up to 2 cycles; 1 cycle is 28 days)
Population: ITT Population. Analyzed population was the number of participants in Cohorts 1-3 from whom evaluable data were obtained. The Postconsidaltion cohort involved the participants in maintenance and were excluded.
Secondary
Dose-Escalation and Expansion Phases: Percentage of Participants With a Negative Minimal Residual Disease (MRD) Status at the End of Induction Treatment
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.
Time frame: At the end of induction treatment (up to 2 cycles; 1 cycle is 28 days)
Population: ITT Population. Analyzed population was the number of participants in Cohorts 1-3 from whom evaluable data were obtained. The Postconsidaltion cohort involved the participants in maintenance and were excluded.
Secondary
Kaplan-Meier Estimate of the Percentage of Participants in Event-Free Survival
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
Time frame: Up to 5 years
Population: Due to the insufficient enrollment of the planned Analysis Population, the planned outcome measurements were not conducted and result data were not collected.
Secondary
Kaplan-Meier Estimate of the Percentage of Participants in Overall Survival
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
Time frame: Up to 5 years
Population: Due to the insufficient enrollment of the planned Analysis Population, the planned outcome measurements were not conducted and result data were not collected.
Secondary
Kaplan-Meier Estimate of the Percentage of Participants in Relapse-Free Survival in Those Who Achieve Remission (CR, CRi, CRp, or CRh)
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
Time frame: Up to 5 years
Population: Due to the insufficient enrollment of the planned Analysis Population, the planned outcome measurements were not conducted and result data were not collected.
Secondary
Maximum Observed Plasma Concentration (Cmax) of Idasanutlin
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
Time frame: 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)
Population: Due to the insufficient enrollment of the planned Analysis Population, the planned outcome measurements were not conducted and result data were not collected.
Secondary
Post-Consolidation Phase: Percentage of Participants Converting From MRD-Positive to MRD-Negative Status at Any Time During Treatment
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
Time frame: At the end of maintenance treatment (12 cycles, 1 cycle is 28 days)
Population: Due to the insufficient enrollment of the planned Analysis Population, the planned outcome measurements were not conducted and result data were not collected.
Secondary
t1/2 of Cytarabine
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
Time frame: 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)
Population: Due to the insufficient enrollment of the planned Analysis Population, the planned outcome measurements were not conducted and result data were not collected.
Secondary
t1/2 of Daunorubicin
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
Time frame: Pre-dose and at predefined intervals post-dose on Days 1, 3, and 5 of induction Cycle 1 (1 cycle is 28 days)
Population: Due to the insufficient enrollment of the planned Analysis Population, the planned outcome measurements were not conducted and result data were not collected.
Secondary
Terminal Half-Life (t1/2) of Idasanutlin
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
Time frame: 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)
Population: Due to the insufficient enrollment of the planned Analysis Population, the planned outcome measurements were not conducted and result data were not collected.
Secondary
Total Clearance (CL) of Idasanutlin
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
Time frame: 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)
Population: Due to the insufficient enrollment of the planned Analysis Population, the planned outcome measurements were not conducted and result data were not collected.
Secondary
Volume of Distribution at Steady State (Vss) of Idasanutlin
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
Time frame: 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)
Population: Due to the insufficient enrollment of the planned Analysis Population, the planned outcome measurements were not conducted and result data were not collected.
Secondary
Vss of Cytarabine
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
Time frame: 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)
Population: Due to the insufficient enrollment of the planned Analysis Population, the planned outcome measurements were not conducted and result data were not collected.
Secondary
Vss of Daunorubicin
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
Time frame: Pre-dose and at predefined intervals post-dose on Days 1, 3, and 5 of induction Cycle 1 (1 cycle is 28 days)
Population: Due to the insufficient enrollment of the planned Analysis Population, the planned outcome measurements were not conducted and result data were not collected.