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

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

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).

Study Overview

• Status: Terminated
• Conditions: Acute Myeloid Leukemia
• Intervention / Treatment: Drug: Idasanutlin; Drug: Cytarabine; Drug: Daunorubicin; Procedure: Allogeneic Hematopoietic Stem Cell Transplant (Allo-HSCT)

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Australia
  • Victoria
    • Prahan, Victoria, Australia, 3181
      • The Alfred Hospital
  • Western Australia
    • Perth, Western Australia, Australia, 6000
      • Royal Perth Hospital
• France
  • Lyon, France, 69008
    • Centre Leon Berard
  • Marseille, France, 13009
    • Institut Paoli Calmettes
  • Nantes, France, 44093
    • CHU de Nantes - Hôtel Dieu
  • Paris, France, 75475
    • Hôpital Saint-Louis
  • Toulouse, France, 31059
    • Institut Universitaire du cancer de Toulouse-Oncopole
• Italy
  • Emilia-Romagna
    • Meldola, Emilia-Romagna, Italy, 47014
      • Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST); Onco-Ematologia
  • Lombardia
    • Bergamo, Lombardia, Italy, 24127
      • ASST Papa Giovanni XXIII; Dipartimento Interaziendale di Farmacia Clinica
• Spain
  • Barcelona, Spain, 08035
    • Hospital Universitario Vall d'Hebron
  • Barcelona, Spain, 08025
    • Hospital De La Santa Creu I Sant Pau
  • Madrid, Spain, 28040
    • Hospital Universitario Fundacion Jimenez Diaz.
  • Sevilla, Spain, 41013
    • Hospital Universitario Virgen del Rocío; Servicio de Neuropediatra
  • Valencia, Spain
    • Hospital Universitari i Politècnic La Fe
• United States
  • California
    • Los Angeles, California, United States, 90095
      • UCLA Jonsson Comprehensive Cancer Center
  • Colorado
    • Denver, Colorado, United States, 80218
      • Sarah Cannon Research Institute at HealthONE
  • Illinois
    • Chicago, Illinois, United States, 60637-1447
      • Robert H. Lurie Comprehensive Cancer Center of Northwestern University
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa Hospitals and Clinics; Investigational Drug Services
  • Kansas
    • Fairway, Kansas, United States, 66205
      • University of Kansas Clinical Research Center; Clinical Trials Office
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
  • New York
    • Brooklyn, New York, United States, 11203
      • State University of NY
    • New York, New York, United States, 10029
      • Icahn School of Medicine at Mount Sinai
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest Baptist Medical Center
  • Ohio
    • Columbus, Ohio, United States, 43210
      • The Ohio State University Comprehensive Cancer Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University Hospital
  • Texas
    • Houston, Texas, United States, 77030-4009
      • The University of Texas MD Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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.	Drug: 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.; Other Names: RO5503781; RG7388; Drug: 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.; Drug: 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.; Procedure: 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.
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.	Drug: 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.; Other Names: RO5503781; RG7388
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.	Drug: 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.; Other Names: RO5503781; RG7388; Drug: 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.; Drug: 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.; Procedure: 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.
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.	Drug: 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.; Other Names: RO5503781; RG7388; Drug: 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.; Drug: 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.; Procedure: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	Cycle 1 of induction treatment (1 cycle is 28 days)
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.	From Baseline until 28 days after the final dose of study drug (up to 2 years)
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	From Baseline until 28 days after the final dose of study drug (up to 2 years)
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	Day 1 of each treatment cycle (1 cycle is 28 days) and at study drug discontinuation (up to 2 years)
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	Baseline, Day 1 of each treatment cycle (1 cycle is 28 days), and at study drug discontinuation (up to 2 years)
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	Baseline, Day 1 of each treatment cycle (1 cycle is 28 days), and at study drug discontinuation (up to 2 years)
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	Baseline, Day 1 of each treatment cycle (1 cycle is 28 days), and at study drug discontinuation (up to 2 years)
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	Baseline, Day 1 of each treatment cycle (1 cycle is 28 days), and at study drug discontinuation (up to 2 years)
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	Day 1 of each treatment cycle (1 cycle is 28 days) and at study drug discontinuation (up to 2 years)
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	Baseline, Day 1 of each treatment cycle (1 cycle is 28 days), and at study drug discontinuation (up to 2 years)
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	Baseline, Day 1 of each treatment cycle (1 cycle is 28 days), and at study drug discontinuation (up to 2 years)
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	Baseline, Day 1 of each treatment cycle (1 cycle is 28 days), and at study drug discontinuation (up to 2 years)
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	Baseline, Day 1 of each treatment cycle (1 cycle is 28 days), and at study drug discontinuation (up to 2 years)
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	Day 1 of each treatment cycle (1 cycle is 28 days) and at study drug discontinuation (up to 2 years)
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	Baseline, Day 1 of each treatment cycle (1 cycle is 28 days), and at study drug discontinuation (up to 2 years)
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	Baseline, Day 1 of each treatment cycle (1 cycle is 28 days), and at study drug discontinuation (up to 2 years)
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	Baseline, Day 1 of each treatment cycle (1 cycle is 28 days), and at study drug discontinuation (up to 2 years)
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	Baseline, Day 1 of each treatment cycle (1 cycle is 28 days), and at study drug discontinuation (up to 2 years)
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.	At the end of induction treatment (up to 2 cycles; 1 cycle is 28 days)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	At the end of induction treatment (up to 2 cycles; 1 cycle is 28 days)
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.	At the end of induction treatment (up to 2 cycles; 1 cycle is 28 days)
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.	At the end of induction treatment (up to 2 cycles; 1 cycle is 28 days)
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	At the end of maintenance treatment (12 cycles, 1 cycle is 28 days)
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	Up to 5 years
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	Up to 5 years
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	Up to 5 years
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	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)
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	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)
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	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)
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	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)
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	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)
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	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)
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	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)
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	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)
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	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)
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	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)
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	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)
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	Pre-dose and at predefined intervals post-dose on Days 1, 3, and 5 of induction Cycle 1 (1 cycle is 28 days)
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	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)
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	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)
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	Pre-dose and at predefined intervals post-dose on Days 1, 3, and 5 of induction Cycle 1 (1 cycle is 28 days)
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	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)
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	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)
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	Pre-dose and at predefined intervals post-dose on Days 1, 3, and 5 of induction Cycle 1 (1 cycle is 28 days)
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	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)
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	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)
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	Pre-dose and at predefined intervals post-dose on Days 1, 3, and 5 of induction Cycle 1 (1 cycle is 28 days)
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	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)
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	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)
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	Pre-dose and at predefined intervals post-dose on Days 1, 3, and 5 of induction Cycle 1 (1 cycle is 28 days)

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start (Actual): March 25, 2019
• Primary Completion (Actual): September 10, 2020
• Study Completion (Actual): September 10, 2020

Study Registration Dates

• First Submitted: February 20, 2019
• First Submitted That Met QC Criteria: February 20, 2019
• First Posted (Actual): February 21, 2019

Study Record Updates

• Last Update Posted (Actual): June 21, 2022
• Last Update Submitted That Met QC Criteria: June 16, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Keywords: AML
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antibiotics, Antineoplastic; Cytarabine; Daunorubicin
• Other Study ID Numbers: GO40800; 2018-002964-25 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

IPD Plan Description

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).

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No