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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03850535




Registration number
NCT03850535
Ethics application status
Date submitted
20/02/2019
Date registered
21/02/2019
Date last updated
12/08/2019

Titles & IDs
Public title
A Study Evaluating the Safety and Efficacy of Idasanutlin in Combination With Cytarabine and Daunorubicin in Patients Newly Diagnosed With Acute Myeloid Leukemia (AML) and the Safety and Efficacy of Idasanutlin in the Maintenance of First AML Complete Remission
Scientific title
A Phase Ib/II Study Evaluating the Safety and Efficacy of Idasanutlin in Combination With Cytarabine and Daunorubicin in Patients Newly Diagnosed With Acute Myeloid Leukemia (AML) and the Safety and Efficacy of Idasanutlin in the Maintenance of First AML Complete Remission
Secondary ID [1] 0 0
2018-002964-25
Secondary ID [2] 0 0
GO40800
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Acute Myeloid Leukemia 0 0
Condition category
Condition code
Cancer 0 0 0 0
Leukaemia - Acute leukaemia
Cancer 0 0 0 0
Leukaemia - Chronic leukaemia
Cancer 0 0 0 0
Children's - Leukaemia & Lymphoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Idasanutlin
Treatment: Drugs - Cytarabine
Treatment: Drugs - Daunorubicin
Treatment: Surgery - Allogeneic Hematopoietic Stem Cell Transplant (Allo-HSCT)

Experimental: Dose-Escalation Phase - Participants with newly diagnosed, previously untreated, favorable or intermediate risk AML (according to European LeukemiaNet [ELN] 2017 criteria) will undergo the treatment sequence of induction, consolidation, and maintenance. For induction, participants will be treated with idasanutlin plus cytarabine and daunorubicin. At the investigator's discretion for consolidation, either participants will be treated with idasanutlin and cytarabine or they will undergo Allo-HSCT. For maintenance, participants will be treated with single-agent idasanutlin.

Experimental: Post-Consolidation Phase - Participants who are idasanutlin treatment-naive, had received induction and chemotherapy consolidation for AML outside of the study, and were in minimal residual disease (MRD)-positive remission after induction will be enrolled in this cohort to receive maintenance treatment with single-agent idasanutlin.

Experimental: Expansion Phase: Favorable/Intermediate-Risk AML - Participants with newly diagnosed, previously untreated, favorable or intermediate risk AML (according to ELN 2017 criteria) will undergo the treatment sequence of induction, consolidation, and maintenance. For induction, participants will be treated with idasanutlin (at the recommended Phase 2 dose) plus cytarabine and daunorubicin. At the investigator's discretion for consolidation, either participants will be treated with idasanutlin and cytarabine or they will undergo Allo-HSCT. For maintenance, participants will be treated with single-agent idasanutlin.

Experimental: Expansion Phase: High-Risk AML - Participants with newly diagnosed, previously untreated, high-risk AML (defined as adverse risk according to ELN 2017 criteria, and secondary AML) will undergo the treatment sequence of induction, consolidation, and maintenance. For induction, participants will be treated with idasanutlin (at the recommended Phase 2 dose) plus cytarabine and daunorubicin. At the investigator's discretion for consolidation, either participants will be treated with idasanutlin and cytarabine or they will undergo Allo-HSCT. For maintenance, participants will be treated with single-agent idasanutlin.


Treatment: Drugs: Idasanutlin
Participants will self-administer idasanutlin tablets by mouth (PO) once daily (QD) for 5 days of each 28-day treatment cycle for up to 2 cycles of induction, up to 4 cycles of consolidation, and 12 cycles of maintenance, according to the study's protocol.

Treatment: Drugs: Cytarabine
Cytarabine will be administered for 7 days of each 28-day cycle for up to 2 cycles of induction treatment at a dose of 200 milligrams per meter squared (mg/m^2) of body surface area, once daily (QD) by intravenous (IV) infusion. At the investigator's discretion, cytarabine will also be administered as part of chemotherapy consolidation at a dose of 1.5 g/m^2 QD as IV infusion for 5 days of each 28-day cycle and for up to 4 cycles of treatment.

Treatment: Drugs: Daunorubicin
Daunorubicin will be administered for 3 days of each 28-day cycle for up to 2 cycles of induction treatment at a dose of 60 mg/m^2 QD as IV infusion.

Treatment: Surgery: Allogeneic Hematopoietic Stem Cell Transplant (Allo-HSCT)
After induction treatment, participants who achieve remission will either receive chemotherapy consolidation treatment or undergo Allo-HSCT (as per local guidelines) at the investigator's discretion.

Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Treatment: Surgery
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Dose Escalation Phase: Number of Participants with Dose-Limiting Toxicities (DLTs) During the First Cycle of Induction Treatment
Timepoint [1] 0 0
Cycle 1 of induction treatment (1 cycle is 28 days)
Primary outcome [2] 0 0
Number of Participants with at Least One Adverse Event
Timepoint [2] 0 0
From Baseline until 28 days after the final dose of study drug (up to 2 years)
Primary outcome [3] 0 0
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)
Timepoint [3] 0 0
From Baseline until 28 days after the final dose of study drug (up to 2 years)
Primary outcome [4] 0 0
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 recall period is over the past 7 days.
Timepoint [4] 0 0
Day 1 of each treatment cycle (1 cycle is 28 days) and at study drug discontinuation (up to 2 years)
Primary outcome [5] 0 0
Change from Baseline Over Time in Reported Frequency of Nausea, as Assessed Through Use of the NCI PRO-CTCAE - Frequency of nausea is reported by participants on a 5-point Likert-type scale (Never, Rarely, Occasionally, Frequently, or Almost Constantly). The recall period is over the past 7 days.
Timepoint [5] 0 0
Baseline, Day 1 of each treatment cycle (1 cycle is 28 days), and at study drug discontinuation (up to 2 years)
Primary outcome [6] 0 0
Change from Baseline Over Time in Reported Severity of Nausea, as Assessed Through Use of the NCI PRO-CTCAE - Severity of nausea is reported by participants on a 5-point Likert-type scale (None, Mild, Moderate, Severe, or Very Severe). The recall period is over the past 7 days.
Timepoint [6] 0 0
Baseline, Day 1 of each treatment cycle (1 cycle is 28 days), and at study drug discontinuation (up to 2 years)
Primary outcome [7] 0 0
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 - Degree of interference with daily function caused by nausea is reported by participants on a 5-point Likert-type scale (Not At All, A Little Bit, Somewhat, Quite A Bit, or Very Much). The recall period is over the past 7 days.
Timepoint [7] 0 0
Baseline, Day 1 of each treatment cycle (1 cycle is 28 days), and at study drug discontinuation (up to 2 years)
Primary outcome [8] 0 0
Change from Baseline Over Time in Overall Score for Nausea, as Assessed Through Use of the NCI PRO-CTCAE
Timepoint [8] 0 0
Baseline, Day 1 of each treatment cycle (1 cycle is 28 days), and at study drug discontinuation (up to 2 years)
Primary outcome [9] 0 0
Number of Participants Reporting Presence or Absence of Vomiting Over Time, as Assessed Through Use of the NCI PRO-CTCAE - The recall period is over the past 7 days.
Timepoint [9] 0 0
Day 1 of each treatment cycle (1 cycle is 28 days) and at study drug discontinuation (up to 2 years)
Primary outcome [10] 0 0
Change from Baseline Over Time in Reported Frequency of Vomiting, as Assessed Through Use of the NCI PRO-CTCAE - Frequency of vomiting is reported by participants on a 5-point Likert-type scale (Never, Rarely, Occasionally, Frequently, or Almost Constantly). The recall period is over the past 7 days.
Timepoint [10] 0 0
Baseline, Day 1 of each treatment cycle (1 cycle is 28 days), and at study drug discontinuation (up to 2 years)
Primary outcome [11] 0 0
Change from Baseline Over Time in Reported Severity of Vomiting, as Assessed Through Use of the NCI PRO-CTCAE - Severity of vomiting is reported by participants on a 5-point Likert-type scale (None, Mild, Moderate, Severe, or Very Severe). The recall period is over the past 7 days.
Timepoint [11] 0 0
Baseline, Day 1 of each treatment cycle (1 cycle is 28 days), and at study drug discontinuation (up to 2 years)
Primary outcome [12] 0 0
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 - Degree of interference with daily function caused by vomiting is reported by participants on a 5-point Likert-type scale (Not At All, A Little Bit, Somewhat, Quite A Bit, or Very Much). The recall period is over the past 7 days.
Timepoint [12] 0 0
Baseline, Day 1 of each treatment cycle (1 cycle is 28 days), and at study drug discontinuation (up to 2 years)
Primary outcome [13] 0 0
Change from Baseline Over Time in Overall Score for Vomiting, as Assessed Through Use of the NCI PRO-CTCAE
Timepoint [13] 0 0
Baseline, Day 1 of each treatment cycle (1 cycle is 28 days), and at study drug discontinuation (up to 2 years)
Primary outcome [14] 0 0
Number of Participants Reporting Presence or Absence of Diarrhea Over Time, as Assessed Through Use of the NCI PRO-CTCAE Over Time - The recall period is over the past 7 days.
Timepoint [14] 0 0
Day 1 of each treatment cycle (1 cycle is 28 days) and at study drug discontinuation (up to 2 years)
Primary outcome [15] 0 0
Change from Baseline in Reported Frequency of Diarrhea Over Time, as Assessed Through Use of the NCI PRO-CTCAE - Frequency of diarrhea is reported by participants on a 5-point Likert-type scale (Never, Rarely, Occasionally, Frequently, or Almost Constantly). The recall period is over the past 7 days.
Timepoint [15] 0 0
Baseline, Day 1 of each treatment cycle (1 cycle is 28 days), and at study drug discontinuation (up to 2 years)
Primary outcome [16] 0 0
Change from Baseline in Reported Severity of Diarrhea Over Time, as Assessed Through Use of the NCI PRO-CTCAE - Severity of diarrhea is reported by participants on a 5-point Likert-type scale (None, Mild, Moderate, Severe, or Very Severe). The recall period is over the past 7 days.
Timepoint [16] 0 0
Baseline, Day 1 of each treatment cycle (1 cycle is 28 days), and at study drug discontinuation (up to 2 years)
Primary outcome [17] 0 0
Change from Baseline in Reported Degree of Interference with Daily Function Caused by Diarrhea Over Time, as Assessed Through Use of the NCI PRO-CTCAE - Degree of interference with daily function caused by diarrhea is reported by participants on a 5-point Likert-type scale (Not At All, A Little Bit, Somewhat, Quite A Bit, or Very Much). The recall period is over the past 7 days.
Timepoint [17] 0 0
Baseline, Day 1 of each treatment cycle (1 cycle is 28 days), and at study drug discontinuation (up to 2 years)
Primary outcome [18] 0 0
Change from Baseline in Overall Score for Diarrhea Over Time, as Assessed Through Use of the NCI PRO-CTCAE
Timepoint [18] 0 0
Baseline, Day 1 of each treatment cycle (1 cycle is 28 days), and at study drug discontinuation (up to 2 years)
Primary outcome [19] 0 0
Percentage of Participants with a Complete Remission (CR) at the End of Induction Treatment, Among Those Treated at the Recommended Phase 2 Dose
Timepoint [19] 0 0
At the end of induction treatment (up to 2 cycles; 1 cycle is 28 days)
Secondary outcome [1] 0 0
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
Timepoint [1] 0 0
At the end of induction treatment (up to 2 cycles; 1 cycle is 28 days)
Secondary outcome [2] 0 0
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
Timepoint [2] 0 0
At the end of induction treatment (up to 2 cycles; 1 cycle is 28 days)
Secondary outcome [3] 0 0
Dose-Escalation and Expansion Phases: Percentage of Participants with a Negative Minimal Residual Disease (MRD) Status at the End of Induction Treatment
Timepoint [3] 0 0
At the end of induction treatment (up to 2 cycles; 1 cycle is 28 days)
Secondary outcome [4] 0 0
Post-Consolidation Phase: Percentage of Participants Converting from MRD-Positive to MRD-Negative Status at Any Time During Treatment
Timepoint [4] 0 0
At the end of maintenance treatment (12 cycles, 1 cycle is 28 days)
Secondary outcome [5] 0 0
Kaplan-Meier Estimate of the Percentage of Participants in Event-Free Survival
Timepoint [5] 0 0
Up to 5 years
Secondary outcome [6] 0 0
Kaplan-Meier Estimate of the Percentage of Participants in Overall Survival
Timepoint [6] 0 0
Up to 5 years
Secondary outcome [7] 0 0
Kaplan-Meier Estimate of the Percentage of Participants in Relapse-Free Survival in Those who Achieve Remission (CR, CRi, CRp, or CRh)
Timepoint [7] 0 0
Up to 5 years
Secondary outcome [8] 0 0
Change from Baseline Over Time in the Participant-Reported Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Questionnaire Total Score - The FACIT-Fatigue (Version 4) consists of 13 items that assess fatigue using a 7-day recall period. Items are scored on a 0 ("not at all") to 4 ("very much so") response scale. Relevant items are reverse scored, and all items are summed to create total scores where higher scores are indicative of better functioning (i.e., less fatigue).
Timepoint [8] 0 0
Baseline, Day 1 of each cycle of induction and consolidation (1 cycle is 28 days), every 3 months starting at Cycle 1 of maintenance, and at study drug discontinuation (up to 2 years)
Secondary outcome [9] 0 0
Change from Baseline Over Time in Physical Function Scale Score of the Participant-Reported European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaire, Core 30 (EORTC QLQ-C30) - The EORTC QLQ-C30 (Version 3) Physical Function Scale comprises 5 items each scored on a 4-point scale that ranges from "not at all" to "very much". Higher scores are indicative of better functioning.
Timepoint [9] 0 0
Baseline, Day 1 of first induction cycle only, Day 1 of each subsequent treatment cycle (1 cycle is 28 days), and at study drug discontinuation (up to 2 years)
Secondary outcome [10] 0 0
Change from Baseline Over Time in Role Function Scale Score of the Participant-Reported EORTC QLQ-C30 - The EORTC QLQ-C30 (Version 3) Role Function Scale comprises 2 items each scored on a 4-point scale that ranges from "not at all" to "very much". Higher scores are indicative of better functioning.
Timepoint [10] 0 0
Baseline, Day 1 of first induction cycle only, Day 1 of each subsequent treatment cycle (1 cycle is 28 days), and at study drug discontinuation (up to 2 years)
Secondary outcome [11] 0 0
Change from Baseline Over Time in Global Health Status/Quality of Life Scale Score of the Participant-Reported EORTC QLQ-C30 - The EORTC QLQ-C30 (Version 3) Global Health Status/Quality of Life Scale comprises 2 items each scored on a 7-point scale that ranges from "very poor" to "excellent". Higher scores are indicative of better health-related quality of life.
Timepoint [11] 0 0
Baseline, Day 1 of first induction cycle only, Day 1 of each subsequent treatment cycle (1 cycle is 28 days), and at study drug discontinuation (up to 2 years)
Secondary outcome [12] 0 0
Change from Baseline Over Time in Headache Symptom Score of the Participant-Reported European Organisation for Research and Treatment of Cancer (EORTC) Item Library Questionnaire - The EORTC Item Library Headache scale comprises 1 item scored on a 4-point scale that ranges from "not at all" to "very much". Higher scores are indicative of higher symptom severity.
Timepoint [12] 0 0
Baseline, Day 1 of each cycle of induction and consolidation (1 cycle is 28 days), every 3 months starting at Cycle 1 of maintenance, and at study drug discontinuation (up to 2 years)
Secondary outcome [13] 0 0
Change from Baseline Over Time in Dizziness Symptom Score of the Participant-Reported EORTC Item Library Questionnaire - The EORTC Item Library Dizziness scale comprises 1 item scored on a 4-point scale that ranges from "not at all" to "very much". Higher scores are indicative of higher symptom severity.
Timepoint [13] 0 0
Baseline, Day 1 of each cycle of induction and consolidation (1 cycle is 28 days), every 3 months starting at Cycle 1 of maintenance, and at study drug discontinuation (up to 2 years)
Secondary outcome [14] 0 0
Change from Baseline Over Time in Bruising Symptom Score of the Participant-Reported EORTC Item Library Questionnaire - The EORTC Item Library Bruising scale comprises 1 item scored on a 4-point scale that ranges from "not at all" to "very much". Higher scores are indicative of higher symptom severity.
Timepoint [14] 0 0
Baseline, Day 1 of each cycle of induction and consolidation (1 cycle is 28 days), every 3 months starting at Cycle 1 of maintenance, and at study drug discontinuation (up to 2 years)
Secondary outcome [15] 0 0
Change from Baseline Over Time in the European Quality of Life 5-Dimension, 5-Level Questionnaire (EQ-5D-5L) Index Utility Score - The EQ-5D-5L Index Utility score is calculated based on a five-item health state profile that assesses mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Published weighting systems allow for creation of a single summary score for the Index Utility score where overall scores range from 0 to 1, with lower scores representing a higher level of dysfunction.
Timepoint [15] 0 0
Baseline, Day 1 of first induction cycle only, Day 1 of all cycles of consolidation (1 cycle is 28 days), every 3 months starting at Cycle 1 of maintenance, and at study drug discontinuation (up to 2 years)
Secondary outcome [16] 0 0
Change from Baseline Over Time in the EQ-5D-5L Visual Analogue Scale (VAS) Score - The EQ-5D-5L VAS is designed for the participant to rate their current health state on a scale from 0 to 100, where 0 represents the worst imaginable health state and 100 represents the best imaginable health state.
Timepoint [16] 0 0
Baseline, Day 1 of first induction cycle only, Day 1 of all cycles of consolidation (1 cycle is 28 days), every 3 months starting at Cycle 1 of maintenance, and at study drug discontinuation (up to 2 years)
Secondary outcome [17] 0 0
Area Under the Plasma Concentration-Time Curve (AUC) of Idasanutlin
Timepoint [17] 0 0
Pre-dose and at predefined intervals post-dose on Days 1, 3, and 5 of induction Cycle 1; Days 1 and 5 of consolidation Cycle 1; and Days 1 and 5 of maintenance Cycle 1 (1 cycle is 28 days)
Secondary outcome [18] 0 0
AUC of Cytarabine
Timepoint [18] 0 0
Pre-dose and at predefined intervals post-dose on Days 1, 3, and 5 of induction Cycle 1; and Days 1 and 5 of consolidation Cycle 1 (1 cycle is 28 days)
Secondary outcome [19] 0 0
AUC of Daunorubicin
Timepoint [19] 0 0
Pre-dose and at predefined intervals post-dose on Days 1, 3, and 5 of induction Cycle 1 (1 cycle is 28 days)
Secondary outcome [20] 0 0
Maximum Observed Plasma Concentration (Cmax) of Idasanutlin
Timepoint [20] 0 0
Pre-dose and at predefined intervals post-dose on Days 1, 3, and 5 of induction Cycle 1; Days 1 and 5 of consolidation Cycle 1; and Days 1 and 5 of maintenance Cycle 1 (1 cycle is 28 days)
Secondary outcome [21] 0 0
Cmax of Cytarabine
Timepoint [21] 0 0
Pre-dose and at predefined intervals post-dose on Days 1, 3, and 5 of induction Cycle 1; and Days 1 and 5 of consolidation Cycle 1 (1 cycle is 28 days)
Secondary outcome [22] 0 0
Cmax of Daunorubicin
Timepoint [22] 0 0
Pre-dose and at predefined intervals post-dose on Days 1, 3, and 5 of induction Cycle 1 (1 cycle is 28 days)
Secondary outcome [23] 0 0
Total Clearance (CL) of Idasanutlin
Timepoint [23] 0 0
Pre-dose and at predefined intervals post-dose on Days 1, 3, and 5 of induction Cycle 1; Days 1 and 5 of consolidation Cycle 1; and Days 1 and 5 of maintenance Cycle 1 (1 cycle is 28 days)
Secondary outcome [24] 0 0
CL of Cytarabine
Timepoint [24] 0 0
Pre-dose and at predefined intervals post-dose on Days 1, 3, and 5 of induction Cycle 1; and Days 1 and 5 of consolidation Cycle 1 (1 cycle is 28 days)
Secondary outcome [25] 0 0
CL of Daunorubicin
Timepoint [25] 0 0
Pre-dose and at predefined intervals post-dose on Days 1, 3, and 5 of induction Cycle 1 (1 cycle is 28 days)
Secondary outcome [26] 0 0
Volume of Distribution at Steady State (Vss) of Idasanutlin
Timepoint [26] 0 0
Pre-dose and at predefined intervals post-dose on Days 1, 3, and 5 of induction Cycle 1; Days 1 and 5 of consolidation Cycle 1; and Days 1 and 5 of maintenance Cycle 1 (1 cycle is 28 days)
Secondary outcome [27] 0 0
Vss of Cytarabine
Timepoint [27] 0 0
Pre-dose and at predefined intervals post-dose on Days 1, 3, and 5 of induction Cycle 1; and Days 1 and 5 of consolidation Cycle 1 (1 cycle is 28 days)
Secondary outcome [28] 0 0
Vss of Daunorubicin
Timepoint [28] 0 0
Pre-dose and at predefined intervals post-dose on Days 1, 3, and 5 of induction Cycle 1 (1 cycle is 28 days)
Secondary outcome [29] 0 0
Terminal Half-Life (t1/2) of Idasanutlin
Timepoint [29] 0 0
Pre-dose and at predefined intervals post-dose on Days 1, 3, and 5 of induction Cycle 1; Days 1 and 5 of consolidation Cycle 1; and Days 1 and 5 of maintenance Cycle 1 (1 cycle is 28 days)
Secondary outcome [30] 0 0
t1/2 of Cytarabine
Timepoint [30] 0 0
Pre-dose and at predefined intervals post-dose on Days 1, 3, and 5 of induction Cycle 1; and Days 1 and 5 of consolidation Cycle 1 (1 cycle is 28 days)
Secondary outcome [31] 0 0
t1/2 of Daunorubicin
Timepoint [31] 0 0
Pre-dose and at predefined intervals post-dose on Days 1, 3, and 5 of induction Cycle 1 (1 cycle is 28 days)

Eligibility
Key inclusion criteria
Inclusion Criteria for All Study Phases:

- Eastern Cooperative Oncology Group (ECOG) performance status =2

- Adequate hepatic and renal function

- For women of childbearing potential: agreement to remain abstinent (refrain from
heterosexual intercourse) or use contraceptive measures, and agreement to refrain from
donating eggs with a failure rate of <1% per year during the treatment period and for
at least 6 months after the final dose of idasanutlin, cytarabine, or daunorubicin.
Women must refrain from donating eggs during this same period.

- For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use
contraceptive, measures, and agreement to refrain from donating sperm that together
result in a failure rate of <1% per year during the treatment period and for 6 months
after the final dose of idasanutlin, cytarabine, or daunorubicin. Men must refrain
from donating sperm during this same period.

Inclusion Criteria for Patients in the Dose-Escalation and Expansion Phases:

- Documented/confirmed newly diagnosed acute myeloid leukemia (AML) not previously treated
according to World Health Organization (WHO)

Inclusion Criteria for Patients in the Post-Consolidation Phase:

- Documented/confirmed AML according to WHO in remission after induction, within 21 days of
end of last chemotherapy consolidation cycle, and were minimum residual disease (MRD)
positive at the end of induction as per local laboratory assessment
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion Criteria for All Study Phases:

- Clinical evidence of central nervous system (CNS) leukemia

- Any Grade =2 non-hematologic toxicities prior to starting therapy

- Current treatment with any other investigational or commercial agents or therapies
administered with the intention to treat their malignancy with the exception of
hydroxyurea (HU) or 6-mercaptopurine (6-MP)

- Treatment-related AML

- Acute promyelocytic leukemia

- History of other malignancy that could affect compliance with the protocol or
interpretation of results

- Any severe and/or uncontrolled medical conditions or other conditions that could
affect their participation in the study, impair the ability of the investigator to
evaluate the patient, or impair the patient's ability to complete the study

- Echocardiogram (ECHO) or multiple-gated acquisition (MUGA) scan showing ejection
fraction =40%

- Non-malignant medical illnesses that are uncontrolled or whose control may be
jeopardized by this study treatment, such as hereditary coagulation disorders,
insulin-dependent diabetes mellitus not optimally controlled with medical management
(e.g., presence of ketoacidosis), or active GI conditions affecting absorption

- Infection considered by the investigator to be clinically uncontrolled or of
unacceptable risk to the patient upon the induction of neutropenia, that is, patients
who are or should be on antimicrobial agents for the treatment of active infection

- Febrile patients within 72 hours of study treatment initiation

- Patients with a history of active or chronic infectious hepatitis unless serology
demonstrates clearance of infection

- Patients who are unable to interrupt treatment with moderate to strong CYP2C8 inducers
and inhibitors

- Patients who are unable to temporarily interrupt treatment with oral or parenteral
anticoagulants/anti-platelet agents during treatment phase

- Patients who have a history of clinically significant liver cirrhosis

- Patients with extramedullary AML with no evidence of systemic involvement

- Pregnant or breastfeeding patients

- Known history of HIV-positive status

- Patients who might refuse to receive blood products and/or have a hypersensitivity to
blood products

- Prior treatment with an MDM2 antagonist

- Patients with clinically relevant QTc prolongation, a family history of long QT
syndrome

Exclusion Criteria for Patients in the Phase Ib Dose-Escalation Phase:

- Adverse risk patients as per European LeukemiaNet (ELN) 2017 criteria

Exclusion Criteria for Patients in Phase Ib Post-Consolidation Phase:

- Any ongoing Grade =2 hematologic adverse events prior to starting therapy

- Previous hematopoietic stem cell transplant (HSCT)

Exclusion Criteria for Patients in the Dose-Escalation Phase and Patients in the
Favorable/Intermediate-Risk Cohort of the Expansion Phase:

- Secondary AML, defined as AML evolving from antecedent hematologic disorder (AHD)

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 1/Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
SA,VIC,WA
Recruitment hospital [1] 0 0
Flinders Medical Centre - Bedford Park
Recruitment hospital [2] 0 0
The Alfred Hospital - Prahan
Recruitment hospital [3] 0 0
Royal Perth Hospital - Perth
Recruitment postcode(s) [1] 0 0
5042 - Bedford Park
Recruitment postcode(s) [2] 0 0
3181 - Prahan
Recruitment postcode(s) [3] 0 0
6000 - Perth
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
Illinois
Country [4] 0 0
United States of America
State/province [4] 0 0
Iowa
Country [5] 0 0
United States of America
State/province [5] 0 0
Kansas
Country [6] 0 0
United States of America
State/province [6] 0 0
Massachusetts
Country [7] 0 0
United States of America
State/province [7] 0 0
New York
Country [8] 0 0
United States of America
State/province [8] 0 0
North Carolina
Country [9] 0 0
United States of America
State/province [9] 0 0
Ohio
Country [10] 0 0
United States of America
State/province [10] 0 0
Pennsylvania
Country [11] 0 0
United States of America
State/province [11] 0 0
Texas
Country [12] 0 0
France
State/province [12] 0 0
Lyon
Country [13] 0 0
France
State/province [13] 0 0
Marseille
Country [14] 0 0
France
State/province [14] 0 0
Nantes
Country [15] 0 0
France
State/province [15] 0 0
Paris
Country [16] 0 0
France
State/province [16] 0 0
Toulouse
Country [17] 0 0
Italy
State/province [17] 0 0
Emilia-Romagna
Country [18] 0 0
Italy
State/province [18] 0 0
Lombardia
Country [19] 0 0
Spain
State/province [19] 0 0
Barcelona
Country [20] 0 0
Spain
State/province [20] 0 0
Madrid
Country [21] 0 0
Spain
State/province [21] 0 0
Sevilla
Country [22] 0 0
Spain
State/province [22] 0 0
Valencia

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Hoffmann-La Roche
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This Phase Ib/II, open-label, multicenter, non-randomized study will evaluate the safety,
efficacy, and pharmacokinetics of idasanutlin when it is given in combination with cytarabine
and daunorubicin in induction, in combination with cytarabine in consolidation, and as a
single agent in maintenance for treating participants with acute myeloid leukemia (AML).
Trial website
https://clinicaltrials.gov/show/NCT03850535
Trial related presentations / publications
Public notes

Contacts
Principal investigator
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Clinical Trials
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Hoffmann-La Roche
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Contact person for public queries
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Reference Study ID Number: GO40800 www.roche.com/about_roche/roche_worldwide.htm
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888-662-6728 (U.S. Only)
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global-roche-genentech-trials@gene.com
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT03850535