MIRROS: A Study of Idasanutlin With Cytarabine Versus Cytarabine Plus Placebo in Participants With Relapsed or Refractory Acute Myeloid Leukemia (AML)
Sponsor
Hoffmann-La Roche (Industry)
Overall Status
Terminated
CT.gov ID
NCT02545283
Collaborator
(none)
447
82
2
51.8
5.5
0.1
Study Details
Study Description
Brief Summary
This is a multicenter, double-blind, randomized, placebo-controlled study designed to compare overall survival in participants with relapsed or refractory AML treated with idasanutlin in combination with cytarabine versus participants treated with placebo and cytarabine. Participants will receive induction treatment with idasanutlin/placebo and cytarabine (Cycle 1). Responding participants may continue to receive a maximum of further two cycles of consolidation (Cycle 2 and Cycle 3). Complete remission (CR), CR with incomplete platelet count recovery (CRp), overall remission rate (ORR), event-free survival (EFS) and percentage of participants with an allogeneic hematopoietic stem cell transplant (HSCT) will also be compared between treatment arms. This study will include participants with and without TP53 wild type (TP53 WT) mutations.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
447 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Treatment
Official Title:
A Multicenter, Double-Blind, Randomized, Placebo-Controlled, Phase III Study of Idasanutlin, an MDM2 Antagonist, With Cytarabine Versus Cytarabine Plus Placebo in Patients With Relapsed or Refractory Acute Myeloid Leukemia (AML)
Actual Study Start Date
:
Dec 30, 2015
Actual Primary Completion Date
:
Apr 24, 2020
Actual Study Completion Date
:
Apr 24, 2020
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Idasanutlin plus Cytarabine Participants will receive induction therapy idasanutlin and cytarabine for 5 Days followed by 23 days of rest in Cycle 1 (treatment cycle length=28 days). Responding participants may continue with consolidation therapy for a maximum of 2 additional cycles including idasanutlin and cytarabine for 5 days followed by 23 days of rest in each cycle (treatment cycle length=28 days). After each cycle, for participants achieving CRp or complete remission with incomplete blood count recovery (CRi), up to 28 additional days are allowed for blood count recovery, if needed. |
Drug: Cytarabine
Participants will receive cytarabine 1 gram per square meter (g/m^2) intravenous (IV) infusion for 5 days of every treatment cycle.
Drug: Idasanutlin
Participants will receive idasanutlin 300 mg per oral (PO) twice daily (BID) (in Cycle 1) or once daily (QD) (in Cycles 2 and 3) for 5 days of every treatment cycle.
Other Names:
|
| Placebo Comparator: Placebo plus Cytarabine Participants will receive induction therapy idasanutlin matching placebo and cytarabine for 5 days followed by 23 days of rest in Cycle 1 (treatment cycle length=28 days). Responding participants may continue with consolidation therapy for a maximum of 2 additional cycles including idasanutlin matching placebo and cytarabine for 5 days followed by 23 days of rest in each cycle (treatment cycle length=28 days). After each cycle, for participants achieving CRp or CRi, up to 28 additional days are allowed for blood count recovery, if needed. |
Drug: Cytarabine
Participants will receive cytarabine 1 gram per square meter (g/m^2) intravenous (IV) infusion for 5 days of every treatment cycle.
Other: Placebo
Participants will receive idasanutlin matching placebo PO BID or QD for 5 days of every treatment cycle.
|
Outcome Measures
Primary Outcome Measures
- Overall Survival in TP53 WT Population [From randomization to death from any cause (up to approximately 4.5 years)]
P53 tumor protein Wild Type (TP53 WT) population's Overall Survival was compared in participants with relapsed or refractory (R/R) acute myeloid leukemia (AML) who had been randomized to idasanutlin in combination with cytarabine versus those who had been randomized to cytarabine and placebo. The study was terminated because of futility, therefore did not reach the planned end of the study.
Secondary Outcome Measures
- Percentage of Participants in Complete Response (CR) at the End of Induction According to Hematologic Malignancy Response Assessment (HMRA) in TP53 WT Population [At the end of induction (up to Day 56)]
Rate of complete response at the end of induction in the TP53 WT population was compared in participants who had been randomized to idasanutlin in combination with cytarabine versus those who had been randomized to cytarabine and placebo. The design followed a hierarchical statistical testing framework.
- Event-Free Survival (EFS) According to HMRA in TP53 WT Population [From randomization up to treatment failure, relapse, or death from any cause (up to approximately 4.5 years)]
Event Free Survival (EFS) is defined as the time from the date of randomization to whichever occurs first: treatment failure (failure to achieve CR, set as day of final response assessment), relapse from CR, or death from any cause. The study was terminated because of futility, therefore did not reach the planned end of the study. The design followed a hierarchical statistical testing framework.
- Percentage of Participants With Overall Remission (CR, CRp, and CRi) at the End of Induction According to HMRA in TP53 WT Population [At the end of induction (up to Day 56)]
Rate of overall remission (complete remission, complete remission with incomplete hematologic recovery, complete remission with incomplete platelet count recovery) at the end of induction in the TP53 WT population was compared in participants who had been randomized to idasanutlin in combination with cytarabine versus those who had been randomized to cytarabine and placebo. The design followed a hierarchical statistical testing framework.
- Duration of Remission Following CR (DOR) in TP53 WT Population [From achieving CR until relapse or death from any cause (up to approximately 4.5 years)]
DOR is defined for patients achieving complete remission and is the time from clinical remission until relapse or death from any cause, whichever occurs first. For patients with none of these events before time of analysis, DOR is censored at the date of the patient's last response assessment. The Median upper limits were set to 999 because they were not reached and therefore it was Not Evaluable (NE) and the field is numeric only. The study was terminated because of futility, therefore did not reach the planned end of the study.
- Percentage of Participants Undergoing HSCT Following Complete Response (CR), in TP53 WT Population [Baseline up to approximately 4.5 years]
Rate of complete response at the end of induction in mutation-defined subgroups (positive for mutation of FLT3, IDH1 and IDH2, respectively) of the TP53 WT population was compared in participants who had been randomized to idasanutlin in combination with cytarabine versus those who had been randomized to cytarabine and placebo. The study was terminated because of futility, therefore did not reach the planned end of the study.
- Percentage of Participants With Complete Response (CR) in Clinically Actionable Mutation-Defined Subpopulation (FLT3, IDH1 and IDH2) in TP53 WT Population [At the end of induction (up to Day 56)]
Rate of complete response at the end of induction in mutation-defined subgroups (positive for mutation of FLT3, IDH1 and IDH2, respectively) of the TP53 WT population was compared in participants who had been randomized to idasanutlin in combination with cytarabine versus those who had been randomized to cytarabine and placebo.
- Overall Survival in Clinically Actionable Mutation-Defined Subpopulation (FLT3, IDH1 and IDH2) in TP53 WT Population [From randomization to death from any cause (up to approximately 4.5 years)]
Overall survival in mutation-defined subgroups (positive for mutation of FLT3, IDH1 and IDH2 respectively) of the TP53 WT population was compared in participants who had been randomized to idasanutlin in combination with cytarabine versus those who had been randomized to cytarabine and placebo. The Median upper limits were set to 999 because they were not reached and therefore it was Not Evaluable (NE) and the field is numeric only. The study was terminated because of futility, therefore did not reach the planned end of the study.
- Number of Participants Who Experienced at Least One Adverse Event by Severity, According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.03 (NCI-CTCAE v4.03) [Baseline up to approximately 4.5 years]
Participants who experienced at least one Adverse Event by severity, According to National Cancer Institute common terminology criteria for Adverse Events, version 4.03 (NCI-CTCAE v4.03) have been reported. The study was terminated because of futility, therefore did not reach the planned end of the study.
- Number of Participants With Adverse Events Leading to Discontinuation [Baseline up to approximately 4.5 years]
Participants with Adverse Events leading to discontinuation of the study have been reported. The study was terminated because of futility, therefore did not reach the planned end of the study.
- Number of Participants With Adverse Events Leading to Death up to Day 30 [Up to Day 30]
The number of participants with AE resulted by death within 30 days from dosing is reported
- Number of Participants With Adverse Events Leading to Death up to Day 60 [Up to Day 60]
The number of participants with AE resulted by death within 60 days from dosing is reported
- Number of Participants With Clinical Laboratory Abnormalities in Biochemistry Tests at the Greatest Severity, According to NCI-CTCAE v4.03 [Up to Approximately 4.5 Years]
Laboratory parameters for blood biochemistry will be measured and compared with a standard reference range. Values outside the standard reference range are considered abnormalities. A laboratory test result will be reported as an adverse event if it meets any of the following criteria: is accompanied by clinical symptoms; results in a change in study treatment or a medical intervention; or is clinically significant in the investigator's judgment. For each patient, baseline is the last observation prior to initiation of study drug. For each laboratory test, patients with at least 1 post-baseline assessment are included in the analysis. For each cell, the denominator is the number of patients with baseline NCI-CTCAE Grade 0-2 in the specified direction of abnormality, or Grade 1-4 in the opposite direction of abnormality.
- Number of Participants With Clinical Laboratory Abnormalities in Hematology Tests at the Greatest Severity, According to NCI-CTCAE v4.03 [Up to Approximately 4.5 Years]
Laboratory parameters for hematology will be measured and compared with a standard reference range. Values outside the standard reference range are considered abnormalities. A laboratory test result will be reported as an adverse event if it meets any of the following criteria: is accompanied by clinical symptoms; results in a change in study treatment or a medical intervention; or is clinically significant in the investigator's judgment. For each patient, baseline is the last observation prior to initiation of study drug. For each laboratory test, patients with at least 1 post-baseline assessment are included in the analysis. For each cell, the denominator is the number of patients with baseline NCI-CTCAE Grade 0-2 in the specified direction of abnormality, or Grade 1-4 in the opposite direction of abnormality.
- Change From Baseline in Body Temperature Over Time [Baseline; Cycles 1-3, Days 8, 15, 22, 28 (1 cycle is 28 days); and, if incomplete blood count recovery, Days 29-42 and Days 43-56, Cycles 2 -3 Days 1, 8, 15, 22, 28 and 29-56 (max delay between cycles is 56 days)]
Vital signs were measured prior to the infusion while the participant was in a seated position. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. The study was terminated because of futility, therefore did not reach the planned end of study.
- Change From Baseline in Systolic Blood Pressure Over Time [Baseline; Cycles 1-3, Days 8, 15, 22, 28 (1 cycle is 28 days); and, if incomplete blood count recovery, Days 29-42 and Days 43-56, Cycles 2 -3 Days 1, 8, 15, 22, 28 and 29-56 (max delay between cycles is 56 days)]
Vital signs were measured prior to the infusion while the participant was in a seated position. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. The study was terminated because of futility, therefore did not reach the planned end of study.
- Change From Baseline in Diastolic Blood Pressure Over Time [Baseline; Cycles 1-3, Days 8, 15, 22, 28 (1 cycle is 28 days); and, if incomplete blood count recovery, Days 29-42 and Days 43-56, Cycles 2 -3 Days 1, 8, 15, 22, 28 and 29-56 (max delay between cycles is 56 days)]
Vital signs were measured prior to the infusion while the participant was in a seated position. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. The study was terminated because of futility, therefore did not reach the planned end of study.
- Change From Baseline in Pulse Rate Over Time [Baseline; Cycles 1-3, Days 8, 15, 22, 28 (1 cycle is 28 days); and, if incomplete blood count recovery, Days 29-42 and Days 43-56, Cycles 2 -3 Days 1, 8, 15, 22, 28 and 29-56 (max delay between cycles is 56 days)]
Vital signs were measured prior to the infusion while the participant was in a seated position. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. The study was terminated because of futility, therefore did not reach the planned end of study.
- Change From Baseline in Respiratory Rate Over Time [Up to Approximately 4.5 Years]
Vital signs were measured prior to the infusion while the participant was in a seated position. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. The study was terminated because of futility, therefore did not reach the planned end of study.
- Change From Baseline in Heart Rate, as Measured by Electrocardiogram [Baseline; Cycles 1-3 Day 1 (2 hrs pre-dose, post-Cytarabine and 6 hrs post-Idasanutlin/Placebo ); Cycle 1-3 Day 2; Cycle 1 Day 5 (within 2 hrs Idanasanutlin/Placebo, post-Cytarabine and 6 hrs post-Idasanutlin/Placebo), Study Drug Completion]
Single 12-lead ECGs was obtained using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and QTc intervals. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. The study was terminated because of futility, therefore did not reach the planned end of study.
- Change From Baseline in Electrocardiogram Parameters: PQ, PR, RR, QRS, QT and QTcF Intervals [Baseline, Days 1, 2, and 5 of Cycle 1, Days 1, 2 of Cycles 2 and 3 (1 cycle is 28 days), Treatment Discontinuation Visit (28 days after last dose of study drug)]
Single 12-lead ECGs was obtained using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and QTc intervals. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. The study was terminated because of futility, therefore did not reach the planned end of study.
- Total Duration of Study Treatment [Up to 3 cycles (1 cycle is 28 days)]
Participants were planned to be treated up to 3 Cycles.
- Number of Treatment Cycles Started [Up to 3 cycles (1 cycle is 28 days)]
Participants who started the study treatment cycles are reported.
- Cumulative Dose of Idasanutlin and Cytarabine [Up to 3 cycles (1 cycle is 28 days)]
The cumulative doses of idasanutlin and cytaradine are reported.
- Apparent Clearance (CL/F) of Idasanutlin [Cycle 1: Predose (0 hour [Hr]), end of 1-3 Hr cytarabine infusion, 6 Hr postdose on Days 1, 5; Predose (0 Hr) on Day 2; at Days 8, 10; Cycle 2, 3: predose (0 Hr) on Days 2, 5 (predose/postdose: relative to idasanutlin morning dose; cycle length= 28 days)]
Apparent Clearance (CL/F) of Idasanutlin was planned as part of the PK analyses. The Independent Data Monitoring Committee recommended stopping the study for futility based on a lack of OS benefit due to Hazard Ratio (HR) being greater than 1. The benefit-risk profile of idasanutlin combined with 1g/m2 cytarabine in fit R/R AML was not positive, as the observed marginal benefit does not outweigh the risks of idasanutlin in the relapsed or refractory AML population. Therefore the study was prematurely terminated by the sponsor's decision and the result data did not derive.The benefit-risk profile of idasanutlin combined with 1g/m2 cytarabine in fit R/R AML was not positive, as the observed marginal benefit does not outweigh the risks of idasanutlin in the relapsed or refractory AML population. The planned CL/F did not derive for the result data and was not reported.
- Apparent Volume of Distribution (Vd/F) of Idasanutlin [Cycle 1: Predose (0 Hr), end of 1-3 Hr cytarabine infusion, 6 Hr postdose on Days 1, 5; Predose (0 Hr) on Day 2; at Days 8, 10; Cycle 2, 3: predose (0 Hr) on Days 2, 5 (predose/postdose: relative to idasanutlin morning dose; cycle length= 28 days)]
Apparent Volume of Distribution (Vd/F) of Idasanutlin was planned as part of the PK analyses. The Independent Data Monitoring Committee recommended stopping the study for futility based on a lack of OS benefit due to Hazard Ratio (HR) being greater than 1. The benefit-risk profile of idasanutlin combined with 1g/m2 cytarabine in fit R/R AML was not positive, as the observed marginal benefit does not outweigh the risks of idasanutlin in the relapsed or refractory AML population. Therefore the study was prematurely terminated by the sponsor's decision and the result data did not derive.
- Maximum Concentration Observed (Cmax) of Idasanutlin [Cycle 1: Predose (0 Hr), end of 1-3 Hr cytarabine infusion, 6 Hr postdose on Days 1, 5; Predose (0 Hr) on Day 2; at Days 8, 10; Cycle 2, 3: predose (0 Hr) on Days 2, 5 (predose/postdose: relative to idasanutlin morning dose; cycle length= 28 days)]
Maximum Concentration Observed (Cmax) of Idasanutlin was planned as part of the PK analyses. The Independent Data Monitoring Committee recommended stopping the study for futility based on a lack of OS benefit due to Hazard Ratio (HR) being greater than 1. The benefit-risk profile of idasanutlin combined with 1g/m2 cytarabine in fit R/R AML was not positive, as the observed marginal benefit does not outweigh the risks of idasanutlin in the relapsed or refractory AML population. Therefore the study was prematurely terminated by the sponsor's decision and the result data did not derive.
- Steady-State Concentration (Ctrough) of Idasanutlin [Cycle 1: Predose (0 Hr), end of 1-3 Hr cytarabine infusion, 6 Hr postdose on Days 1, 5; Predose (0 Hr) on Day 2; at Days 8, 10; Cycle 2, 3: predose (0 Hr) on Days 2, 5 (predose/postdose: relative to idasanutlin morning dose; cycle length= 28 days)]
Steady-State Concentration (Ctrough) of Idasanutlin was planned as part of the PK analyses. The Independent Data Monitoring Committee recommended stopping the study for futility based on a lack of OS benefit due to Hazard Ratio (HR) being greater than 1. The benefit-risk profile of idasanutlin combined with 1g/m2 cytarabine in fit R/R AML was not positive, as the observed marginal benefit does not outweigh the risks of idasanutlin in the relapsed or refractory AML population. Therefore the study was prematurely terminated by the sponsor's decision and the result data did not derive.
- Area Under the Concentration-Time Curve (AUC) During One Dosing Interval (AUCtau) of Idasanutlin [Cycle 1: Predose (0 Hr), end of 1-3 Hr cytarabine infusion, 6 Hr postdose on Days 1, 5; Predose (0 Hr) on Day 2; at Days 8, 10; Cycle 2, 3: predose (0 Hr) on Days 2, 5 (predose/postdose: relative to idasanutlin morning dose; cycle length= 28 days)]
Area Under the Concentration-Time Curve (AUC) During One Dosing Interval (AUCtau) of Idasanutlin was planned as part of the PK analyses. The Independent Data Monitoring Committee recommended stopping the study for futility based on a lack of OS benefit due to Hazard Ratio (HR) being greater than 1. The benefit-risk profile of idasanutlin combined with 1g/m2 cytarabine in fit R/R AML was not positive, as the observed marginal benefit does not outweigh the risks of idasanutlin in the relapsed or refractory AML population. Therefore the study was prematurely terminated by the sponsor's decision and the result data did not derive.
- AUC From Time Zero to 24 Hours Post Dose (AUC0-24) of Idasanutlin [Cycle 1: Predose (0 Hr), end of 1-3 Hr cytarabine infusion, 6 Hr postdose on Days 1, 5; Predose (0 Hr) on Day 2; at Days 8, 10; Cycle 2, 3: predose (0 Hr) on Days 2, 5 (predose/postdose: relative to idasanutlin morning dose; cycle length= 28 days)]
AUC from Time Zero to 24 Hours Post Dose (AUC0-24) of Idasanutlin was planned as part of the PK analyses. The Independent Data Monitoring Committee recommended stopping the study for futility based on a lack of OS benefit due to Hazard Ratio (HR) being greater than 1. The benefit-risk profile of idasanutlin combined with 1g/m2 cytarabine in fit R/R AML was not positive, as the observed marginal benefit does not outweigh the risks of idasanutlin in the relapsed or refractory AML population. Therefore the study was prematurely terminated by the sponsor's decision and the result data did not derive.
- Half-Life (t 1/2) of Idasanutlin [Cycle 1: Predose (0 Hr), end of 1-3 Hr cytarabine infusion, 6 Hr postdose on Days 1, 5; Predose (0 Hr) on Day 2; at Days 8, 10; Cycle 2, 3: predose (0 Hr) on Days 2, 5 (predose/postdose: relative to idasanutlin morning dose; cycle length= 28 days)]
Half-Life (t 1/2) of Idasanutlin was planned as part of the PK analyses. The Independent Data Monitoring Committee recommended stopping the study for futility based on a lack of OS benefit due to Hazard Ratio (HR) being greater than 1. The benefit-risk profile of idasanutlin combined with 1g/m2 cytarabine in fit R/R AML was not positive, as the observed marginal benefit does not outweigh the risks of idasanutlin in the relapsed or refractory AML population. Therefore the study was prematurely terminated by the sponsor's decision and the result data did not derive.
- Total Clearance (CL) of Cytarabine [Cycle 1: Within 2 Hr pre-cytarabine dose, end of 1-3 Hr cytarabine infusion, 6 Hr post idasanutlin morning dose on Days 1, 5; Within 2 Hr pre-cytarabine dose on Day 2; Cycle 2, 3: Within 2 Hr pre-cytarabine dose on Day 2 (Cycle length= 28 days)]
The Total Clearance (CL) of Cytarabine was planned as part of the PK analyses. The Independent Data Monitoring Committee recommended stopping the study for futility based on a lack of OS benefit due to Hazard Ratio (HR) being greater than 1. The benefit-risk profile of idasanutlin combined with 1g/m2 cytarabine in fit R/R AML was not positive, as the observed marginal benefit does not outweigh the risks of idasanutlin in the relapsed or refractory AML population. Therefore the study was prematurely terminated by the sponsor's decision and the result data did not derive.
- Volume of Distribution (Vd) of Cytarabine [Cycle 1: Within 2 Hr pre-cytarabine dose, end of 1-3 Hr cytarabine infusion, 6 Hr post idasanutlin morning dose on Days 1, 5; Within 2 Hr pre-cytarabine dose on Day 2; Cycle 2, 3: Within 2 Hr pre-cytarabine dose on Day 2 (Cycle length= 28 days)]
The Volume of Distribution (Vd) of Cytarabine was planned as part of the PK analyses. The Independent Data Monitoring Committee recommended stopping the study for futility based on a lack of OS benefit due to Hazard Ratio (HR) being greater than 1. The benefit-risk profile of idasanutlin combined with 1g/m2 cytarabine in fit R/R AML was not positive, as the observed marginal benefit does not outweigh the risks of idasanutlin in the relapsed or refractory AML population. Therefore the study was prematurely terminated by the sponsor's decision and the result data did not derive.
- Change From Baseline in European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Score [Cycle 1 Day 1 (Baseline), Days 8, 15, 28 of Cycle 1, Days 1, 8, 15, 28 of Cycles 2, 3, 28 days after last dose (last dose on Cycle 3 Day 5), thereafter every 3 months until relapse (maximum up to 3.5 years)]
The compliance rate (defined as the number of patients who completed as least 1 question on the measure) at baseline was 56% and 61% for the Idasanutlin arm and the placebo arm, respectively. This compliance rate remained the same post-baseline in both arms. Due to the low compliance rates in both arms during the entire treatment period, the planned analyses were not performed.
- Change From Baseline in EuroQol 5 Dimension 5-Level (EQ-5D-5L) Questionnaire Score [Cycle 1 Day 1 (Baseline), Days 8, 15, 28 of Cycle 1, Days 1, 8, 15, 28 of Cycles 2, 3, 28 days after last dose (last dose on Cycle 3 Day 5), thereafter every 3 months until relapse (maximum up to 3.5 years)]
The compliance rate (defined as the number of patients who completed as least 1 question on the measure) at baseline was 56% and 61% for the Idasanutlin arm and the placebo arm, respectively. Compliance remained the same post-baseline in both arms Due to the low compliance rates in both arms during the entire treatment period, the planned analyses were not performed.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Documented/confirmed first/second refractory/relapsed AML using World Health Organization classification, except acute promyelocytic leukemia
-
No more than 2 prior induction regimens (excluding prior HSCT) in their first line treatment and one must have included cytarabine with an anthracycline (or anthracenedione)
-
Eastern Cooperative Oncology Group performance status of 0 to 2
-
Adequate hepatic and renal function
-
White blood cell (WBC) count at randomization less than or equal to (</=) 50000 cells per cubic millimeter (/mm^3)
Exclusion Criteria:
-
First relapsed participants aged less than (<) 60 years with first CR duration greater than (>) 1 year
-
Participants with prior documented antecedent hematological disorder (AHD)
-
AML secondary to any prior chemotherapy unrelated to leukemia
-
Participants who are either refractory to or relapsed within 90 days of receiving a regimen containing a cumulative dose of greater than or equal to (>/=) 18 g/m^2 of cytarabine
-
Participants who have received allogeneic HSCT within 90 days prior to randomization
-
Participants who have received immunosuppressive therapy for graft versus host disease or for engraftment syndrome after autologous stem cell transplantation within 2 weeks prior to randomization
-
Prior treatment with an Murine Double Minute 2 (MDM2) antagonist
-
Participants receiving any other investigational or commercial agents or therapies administered with the intention to treat their malignancy within 30 days from first receipt of study drug
-
Participants with a history of other malignancy within 5 years prior to screening except for malignancy that has been in remission without treatment for at least 2 years prior to randomization
-
Participants who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study
-
Participants with extramedullary AML with no evidence of systemic involvement
-
Pregnant or breastfeeding participants
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Northwell Health | Great Neck | New York | United States | 11021 |
| 2 | New York Medical College | Hawthorne | New York | United States | 10532 |
| 3 | Ichan School of Medicine at Mount Sinai | New York | New York | United States | 10029 |
| 4 | Abramson Cancer Center; Univ of Pennsylvania | Philadelphia | Pennsylvania | United States | 19104 |
| 5 | Thomas Jefferson University | Philadelphia | Pennsylvania | United States | 19107 |
| 6 | Baylor University Medical Center | Dallas | Texas | United States | 75204 |
| 7 | M.D. Anderson Cancer Center; Department of Hematology | Houston | Texas | United States | 77030 |
| 8 | Canberra Hospital; Haematology Department | Canberra | Australian Capital Territory | Australia | 2605 |
| 9 | Concord Repatriation General Hospital; Haematology | Sydney | New South Wales | Australia | 2139 |
| 10 | Royal Adelaide Hospital; Haematology Clinical Trials | Adelaide | South Australia | Australia | 5000 |
| 11 | Geelong Hospital; Andrew Love Cancer Centre | Geelong | Victoria | Australia | 3220 |
| 12 | Alfred Hospital; Clinical Haematology and Bone Marrow Transplantation | Melbourne | Victoria | Australia | 3004 |
| 13 | Lkh-Univ. Klinikum Graz; Klin. Abt. Für Hämatologie | Graz | Austria | 8036 | |
| 14 | CH Jolimont - Lobbes (Jolimont) | Haine-Saint-Paul | Belgium | 7100 | |
| 15 | CHU Sart-Tilman | Liège | Belgium | 4000 | |
| 16 | AZ Delta (Campus Rumbeke) | Roeselare | Belgium | 8800 | |
| 17 | Juravinski Cancer Clinic; Clinical Trials Department | Hamilton | Ontario | Canada | L8V 5C2 |
| 18 | Helsinki University Central Hospital; Hematology | Helsinki | Finland | 00290 | |
| 19 | Tampere University Hospital; Hematology | Tampere | Finland | 33521 | |
| 20 | Centre Hospitalier Uni Ire; Service Des Maladies Du Sang | Angers Cedex 9 | France | 49933 | |
| 21 | Hopital Claude Huriez; Hematologie | Lille | France | 59037 | |
| 22 | Institut J Paoli I Calmettes; Onco Hematologie 2 | Marseille | France | 13273 | |
| 23 | Hopital Hotel Dieu Et Hme;Hopital De Jour | Nantes | France | 44093 | |
| 24 | Hopital Saint Louis; Oncologie Medicale | Paris | France | 75475 | |
| 25 | HOPITAL SAINT ANTOINE;Hematologie Clinique | Paris | France | 75571 | |
| 26 | Hopital De Haut Leveque; Hematologie Clinique | Pessac | France | 33604 | |
| 27 | Centre Hospitalier Lyon Sud; Hematolgie | Pierre Benite | France | 69495 | |
| 28 | IUCT Oncopole; Hematologie | Toulouse | France | 31059 | |
| 29 | Hopitaux De Brabois; Hematologie Medecine Interne | Vandoeuvre Les Nancy | France | 54511 | |
| 30 | Uniklinik RWTH Aachen; Klinik IV; Klinik Hämatologie, Onkologie, Hämostaseologie und Stamm. | Aachen | Germany | 52074 | |
| 31 | Universitätsklinikum Bonn; Med. Klinik und Poliklinik III; Hämatologie, Onkologie und Rheumatologie | Bonn | Germany | 53127 | |
| 32 | Klinikum Braunschweig; Medizinische Klinik III; Klinik für Hämatologie und Onkologie | Braunschweig | Germany | 38114 | |
| 33 | Klinikum Chemnitz gGmbH Krankenhaus Küchwald Klinik f.Innere Medizin III | Chemnitz | Germany | 09113 | |
| 34 | Universitätsklinikum "Carl Gustav Carus"; Medizinische Klinik und Poliklinik I | Dresden | Germany | 01307 | |
| 35 | Medizinische Hochschule Hannover; Zentrum Innere Medizin; Abt. Hämatologie u. Onkologie | Hannover | Germany | 30625 | |
| 36 | Klinik der Uni zu Köln; I. Med. Klinik | Köln | Germany | 50937 | |
| 37 | Uni. der Johannes Gutenberg-Universitaet Mainz; III. Medizinische Klinik und Poliklinik | Mainz | Germany | 55131 | |
| 38 | Universitätsklinikum Marburg Zentrum f. Innere Medizin | Marburg | Germany | 35043 | |
| 39 | Shaare Zedek Medical Center; Hematology Dept. | Jerusalem | Israel | 9103102 | |
| 40 | Hadassah Ein Karem Hospital; Haematology | Jerusalem | Israel | 9112001 | |
| 41 | Rabin Medical Center-Beilinson Campus;Hematology-Oncology | Petach Tikva | Israel | 4941492 | |
| 42 | Ichilov Sourasky Medical Center; Heamatology | Tel Aviv | Israel | 6423906 | |
| 43 | Ospedale Cardarelli; Divisione Di Ematologia | Napoli | Campania | Italy | 80131 |
| 44 | Az. Osp. S. Orsola Malpighi; Istituto Di Oncologia Seragnoli | Bologna | Emilia-Romagna | Italy | 40138 |
| 45 | Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST); Onco-Ematologia | Meldola | Emilia-Romagna | Italy | 47014 |
| 46 | Az. Osp. S. Maria Delle Croci; U.O. Di Ematologia | Ravenna | Emilia-Romagna | Italy | 48100 |
| 47 | A.O. Universitaria S. Maria Della Misericordia Di Udine; Oncologia; Clinica Ematologica | Udine | Friuli-Venezia Giulia | Italy | 33100 |
| 48 | Az. Osp. Uni Ria Policlinico Tor Vergata; Unita Di Ematologia | Roma | Lazio | Italy | 00133 |
| 49 | IRCCS AOU S.Martino; Clinica Ematologica | Genova | Liguria | Italy | 16132 |
| 50 | ASST PAPA GIOVANNI XXIII; Ematologia | Bergamo | Lombardia | Italy | 24127 |
| 51 | Ospedale San Raffaele, IRCCS | Milano | Lombardia | Italy | 20132 |
| 52 | Asst Grande Ospedale Metropolitano Niguarda; Dipartimento Di Ematologia Ed Oncologia | Milano | Lombardia | Italy | 20162 |
| 53 | A.O. Universitaria San Luigi Gonzaga di Orbassano; Ambulatorio per le Malattie Rare del Polmone | Orbassano (TO) | Piemonte | Italy | 10043 |
| 54 | A.O.U. Citta' Della Salute E Della Scienza-P.O. Molinette;S.C. Ematologia | Torino | Piemonte | Italy | 10126 |
| 55 | Az. Osp. Di Careggi; Divisione Di Ematologia | Firenze | Toscana | Italy | 50135 |
| 56 | Ospedale Santa Chiara; Unita Operativa Di Ematologia | Pisa | Toscana | Italy | 56100 |
| 57 | Pusan National University Hospital | Busan | Korea, Republic of | 49241 | |
| 58 | Chonnam National University Hwasun Hospital | Jeollanam-do | Korea, Republic of | 58128 | |
| 59 | Seoul National University Hospital | Seoul | Korea, Republic of | 03080 | |
| 60 | Samsung Medical Center | Seoul | Korea, Republic of | 06351 | |
| 61 | Seoul St Mary's Hospital | Seoul | Korea, Republic of | 06591 | |
| 62 | Academisch Medisch Centrum; Hematologie | Amsterdam | Netherlands | 1105 AZ | |
| 63 | Academisch Ziekenhuis Maastricht | Maastricht | Netherlands | 6202 AZ | |
| 64 | Auckland city hospital; Auckland Regional Cancer Centre and Blood Service | Auckland | New Zealand | 1023 | |
| 65 | Haukeland Universitetssjukehus; Klinisk forskningspost | Bergen | Norway | 5021 | |
| 66 | Oslo Universitetssykehus HF, Rikshospitalet | Oslo | Norway | 0372 | |
| 67 | Complejo Hospitalario Arnulfo Arias Madrid; Servicio de Hematología | Panama City | Panama | 0824 | |
| 68 | "Hematological Scientific Center | Moscow | Russian Federation | 125167 | |
| 69 | St. Petersburg State Medical University n.a. I.P. Pavlov; Hematology, transfusiology and transplanta | Saint-Petersburg | Russian Federation | 197022 | |
| 70 | FGBU "Federal Medical and Research Center named after V.A.Almazov" Russian Ministry of Health | Sankt-Petersburg | Russian Federation | 197341 | |
| 71 | Hospital de la Santa Creu i Sant Pau; Servicio de Hematologia | Barcelona | Spain | 08025 | |
| 72 | Hospital Clínic i Provincial; Servicio de Hematología y Oncología | Barcelona | Spain | 08036 | |
| 73 | Hospital Univ. 12 de Octubre; Servicio de Hematologia | Madrid | Spain | 28041 | |
| 74 | Hospital Universitario Virgen del Rocio | Sevilla | Spain | 41013 | |
| 75 | Hospital Universitario la Fe; Servicio de Hematologia | Valencia | Spain | 46026 | |
| 76 | Universitätsspital Basel; Hämatologie | Basel | Switzerland | 4031 | |
| 77 | Universitätsspital Zürich Medizin Hämatologie; Klinik für Hämatologie | Zürich | Switzerland | 8091 | |
| 78 | Birmingham Heartlands Hospital | Birmingham | United Kingdom | B9 5SS | |
| 79 | University Hospital of Wales | Cardiff | United Kingdom | CF14 4XW | |
| 80 | St Bartholomew's Hospital | London | United Kingdom | EC1M 6BQ | |
| 81 | Christie Hospital NHS Trust | Manchester | United Kingdom | M20 4BX | |
| 82 | Royal Marsden NHS Foundation Trust | Sutton | United Kingdom | SM2 5PT |
Sponsors and Collaborators
- Hoffmann-La Roche
Investigators
- Study Director: Clinical Trials, Hoffmann-La Roche
Study Documents (Full-Text)
More Information
Publications
None provided.Responsible Party:
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT02545283
Other Study ID Numbers:
- WO29519
- 2014-003065-15
First Posted:
Sep 9, 2015
Last Update Posted:
Jan 11, 2022
Last Verified:
Dec 1, 2021
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | A total of 612 participants were screened, of which 447 patients were randomized as P53 tumor protein Wild Type (TP53 WT) population. TP53WT Population consists of mutation-defined Acute Myeloid Leukemia (AML) subpopulations FLT3, IDH2 and IDH1. |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Placebo Plus Cytarabine | Idasanutlin Plus Cytarabine |
|---|---|---|
| Arm/Group Description | Participants received induction therapy idasanutlin matching placebo and cytarabine for 5 Days followed by 23 days of rest in Cycle 1 (treatment cycle length=28 days). Responding participants may continue with consolidation therapy for a maximum of 2 additional cycles including idasanutlin matching placebo and cytarabine for 5 days followed by 23 days of rest in each cycle (treatment cycle length=28 days). After each cycle, for participants achieving CRp or CRi, up to 28 additional days are allowed for blood count recovery, if needed. | Participants received induction therapy idasanutlin and cytarabine for 5 days followed by 23 days of rest in Cycle 1 (treatment cycle length=28 days). Responding participants may continue with consolidation therapy for a maximum of 2 additional cycles including idasanutlin and cytarabine for 5 days followed by 23 days of rest in each cycle (treatment cycle length=28 days). After each cycle, for participants achieving CRp or complete remission with incomplete blood count recovery (CRi), up to 28 additional days are allowed for blood count recovery, if needed. |
| Period Title: Overall Study | ||
| STARTED | 149 | 298 |
| Received Treatment | 149 | 292 |
| Safety Follow Up | 149 | 292 |
| COMPLETED | 0 | 0 |
| NOT COMPLETED | 149 | 298 |
Baseline Characteristics
| Arm/Group Title | Placebo Plus Cytarabine | Idasanutlin Plus Cytarabine | Total |
|---|---|---|---|
| Arm/Group Description | Participants received induction therapy idasanutlin matching placebo and cytarabine for 5 Days followed by 23 days of rest in Cycle 1 (treatment cycle length=28 days). Responding participants may continue with consolidation therapy for a maximum of 2 additional cycles including idasanutlin matching placebo and cytarabine for 5 days followed by 23 days of rest in each cycle (treatment cycle length=28 days). After each cycle, for participants achieving CRp or CRi, up to 28 additional days are allowed for blood count recovery, if needed. | Participants received induction therapy idasanutlin and cytarabine for 5 days followed by 23 days of rest in Cycle 1 (treatment cycle length=28 days). Responding participants may continue with consolidation therapy for a maximum of 2 additional cycles including idasanutlin and cytarabine for 5 days followed by 23 days of rest in each cycle (treatment cycle length=28 days). After each cycle, for participants achieving CRp or complete remission with incomplete blood count recovery (CRi), up to 28 additional days are allowed for blood count recovery, if needed. | Total of all reporting groups |
| Overall Participants | 149 | 298 | 447 |
| Age (Years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [Years] |
59.9
(12.1)
|
59.4
(13.1)
|
59.6
(12.8)
|
| Sex/Gender, Customized (Count of Participants) | |||
| Male |
86
57.7%
|
163
54.7%
|
249
55.7%
|
| Female |
63
42.3%
|
135
45.3%
|
198
44.3%
|
| Race/Ethnicity, Customized (Count of Participants) | |||
| Hispanic or Latino |
8
5.4%
|
11
3.7%
|
19
4.3%
|
| Not Hispanic or Latino |
112
75.2%
|
231
77.5%
|
343
76.7%
|
| Not Stated |
18
12.1%
|
36
12.1%
|
54
12.1%
|
| Unknown |
11
7.4%
|
20
6.7%
|
31
6.9%
|
| Race/Ethnicity, Customized (Count of Participants) | |||
| Asian |
11
7.4%
|
20
6.7%
|
31
6.9%
|
| Black or African America |
2
1.3%
|
4
1.3%
|
6
1.3%
|
| Native Hawaiian or other |
0
0%
|
1
0.3%
|
1
0.2%
|
| White |
111
74.5%
|
222
74.5%
|
333
74.5%
|
| Unknown |
25
16.8%
|
51
17.1%
|
76
17%
|
Outcome Measures
| Title | Overall Survival in TP53 WT Population |
|---|---|
| Description | P53 tumor protein Wild Type (TP53 WT) population's Overall Survival was compared in participants with relapsed or refractory (R/R) acute myeloid leukemia (AML) who had been randomized to idasanutlin in combination with cytarabine versus those who had been randomized to cytarabine and placebo. The study was terminated because of futility, therefore did not reach the planned end of the study. |
| Time Frame | From randomization to death from any cause (up to approximately 4.5 years) |
Outcome Measure Data
| Analysis Population Description |
|---|
| TP53-WT ITT Population |
| Arm/Group Title | Placebo Plus Cytarabine | Idasanutlin Plus Cytarabine |
|---|---|---|
| Arm/Group Description | Participants received induction therapy idasanutlin matching placebo and cytarabine for 5 Days followed by 23 days of rest in Cycle 1 (treatment cycle length=28 days). Responding participants may continue with consolidation therapy for a maximum of 2 additional cycles including idasanutlin matching placebo and cytarabine for 5 days followed by 23 days of rest in each cycle (treatment cycle length=28 days). After each cycle, for participants achieving CRp or CRi, up to 28 additional days are allowed for blood count recovery, if needed. | Participants received induction therapy idasanutlin and cytarabine for 5 days followed by 23 days of rest in Cycle 1 (treatment cycle length=28 days). Responding participants may continue with consolidation therapy for a maximum of 2 additional cycles including idasanutlin and cytarabine for 5 days followed by 23 days of rest in each cycle (treatment cycle length=28 days). After each cycle, for participants achieving CRp or complete remission with incomplete blood count recovery (CRi), up to 28 additional days are allowed for blood count recovery, if needed. |
| Measure Participants | 123 | 232 |
| Median (95% Confidence Interval) [Months] |
9.13
|
8.28
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo Plus Cytarabine, Idasanutlin Plus Cytarabine |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.5752 |
| Comments | ||
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 1.08 | |
| Confidence Interval |
(2-Sided) 95% 0.81 to 1.45 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Percentage of Participants in Complete Response (CR) at the End of Induction According to Hematologic Malignancy Response Assessment (HMRA) in TP53 WT Population |
|---|---|
| Description | Rate of complete response at the end of induction in the TP53 WT population was compared in participants who had been randomized to idasanutlin in combination with cytarabine versus those who had been randomized to cytarabine and placebo. The design followed a hierarchical statistical testing framework. |
| Time Frame | At the end of induction (up to Day 56) |
Outcome Measure Data
| Analysis Population Description |
|---|
| TP53-WT ITT Population |
| Arm/Group Title | Placebo Plus Cytarabine | Idasanutlin Plus Cytarabine |
|---|---|---|
| Arm/Group Description | Participants received induction therapy idasanutlin matching placebo and cytarabine for 5 Days followed by 23 days of rest in Cycle 1 (treatment cycle length=28 days). Responding participants may continue with consolidation therapy for a maximum of 2 additional cycles including idasanutlin matching placebo and cytarabine for 5 days followed by 23 days of rest in each cycle (treatment cycle length=28 days). After each cycle, for participants achieving CRp or CRi, up to 28 additional days are allowed for blood count recovery, if needed. | Participants received induction therapy idasanutlin and cytarabine for 5 days followed by 23 days of rest in Cycle 1 (treatment cycle length=28 days). Responding participants may continue with consolidation therapy for a maximum of 2 additional cycles including idasanutlin and cytarabine for 5 days followed by 23 days of rest in each cycle (treatment cycle length=28 days). After each cycle, for participants achieving CRp or complete remission with incomplete blood count recovery (CRi), up to 28 additional days are allowed for blood count recovery, if needed. |
| Measure Participants | 123 | 232 |
| Number [Percentage of Participants] |
20.3
13.6%
|
17.1
5.7%
|
| Title | Event-Free Survival (EFS) According to HMRA in TP53 WT Population |
|---|---|
| Description | Event Free Survival (EFS) is defined as the time from the date of randomization to whichever occurs first: treatment failure (failure to achieve CR, set as day of final response assessment), relapse from CR, or death from any cause. The study was terminated because of futility, therefore did not reach the planned end of the study. The design followed a hierarchical statistical testing framework. |
| Time Frame | From randomization up to treatment failure, relapse, or death from any cause (up to approximately 4.5 years) |
Outcome Measure Data
| Analysis Population Description |
|---|
| TP53-WT ITT Population |
| Arm/Group Title | Placebo Plus Cytarabine | Idasanutlin Plus Cytarabine |
|---|---|---|
| Arm/Group Description | Participants received induction therapy idasanutlin matching placebo and cytarabine for 5 Days followed by 23 days of rest in Cycle 1 (treatment cycle length=28 days). Responding participants may continue with consolidation therapy for a maximum of 2 additional cycles including idasanutlin matching placebo and cytarabine for 5 days followed by 23 days of rest in each cycle (treatment cycle length=28 days). After each cycle, for participants achieving CRp or CRi, up to 28 additional days are allowed for blood count recovery, if needed. | Participants received induction therapy idasanutlin and cytarabine for 5 days followed by 23 days of rest in Cycle 1 (treatment cycle length=28 days). Responding participants may continue with consolidation therapy for a maximum of 2 additional cycles including idasanutlin and cytarabine for 5 days followed by 23 days of rest in each cycle (treatment cycle length=28 days). After each cycle, for participants achieving CRp or complete remission with incomplete blood count recovery (CRi), up to 28 additional days are allowed for blood count recovery, if needed. |
| Measure Participants | 123 | 232 |
| Median (95% Confidence Interval) [Weeks] |
6.29
|
4.36
|
| Title | Percentage of Participants With Overall Remission (CR, CRp, and CRi) at the End of Induction According to HMRA in TP53 WT Population |
|---|---|
| Description | Rate of overall remission (complete remission, complete remission with incomplete hematologic recovery, complete remission with incomplete platelet count recovery) at the end of induction in the TP53 WT population was compared in participants who had been randomized to idasanutlin in combination with cytarabine versus those who had been randomized to cytarabine and placebo. The design followed a hierarchical statistical testing framework. |
| Time Frame | At the end of induction (up to Day 56) |
Outcome Measure Data
| Analysis Population Description |
|---|
| TP53-WT ITT Population |
| Arm/Group Title | Placebo Plus Cytarabine | Idasanutlin Plus Cytarabine |
|---|---|---|
| Arm/Group Description | Participants received induction therapy idasanutlin matching placebo and cytarabine for 5 Days followed by 23 days of rest in Cycle 1 (treatment cycle length=28 days). Responding participants may continue with consolidation therapy for a maximum of 2 additional cycles including idasanutlin matching placebo and cytarabine for 5 days followed by 23 days of rest in each cycle (treatment cycle length=28 days). After each cycle, for participants achieving CRp or CRi, up to 28 additional days are allowed for blood count recovery, if needed. | Participants received induction therapy idasanutlin and cytarabine for 5 days followed by 23 days of rest in Cycle 1 (treatment cycle length=28 days). Responding participants may continue with consolidation therapy for a maximum of 2 additional cycles including idasanutlin and cytarabine for 5 days followed by 23 days of rest in each cycle (treatment cycle length=28 days). After each cycle, for participants achieving CRp or complete remission with incomplete blood count recovery (CRi), up to 28 additional days are allowed for blood count recovery, if needed. |
| Measure Participants | 123 | 232 |
| Number [Percentage of Participants] |
38.8
26%
|
22.0
7.4%
|
| Title | Duration of Remission Following CR (DOR) in TP53 WT Population |
|---|---|
| Description | DOR is defined for patients achieving complete remission and is the time from clinical remission until relapse or death from any cause, whichever occurs first. For patients with none of these events before time of analysis, DOR is censored at the date of the patient's last response assessment. The Median upper limits were set to 999 because they were not reached and therefore it was Not Evaluable (NE) and the field is numeric only. The study was terminated because of futility, therefore did not reach the planned end of the study. |
| Time Frame | From achieving CR until relapse or death from any cause (up to approximately 4.5 years) |
Outcome Measure Data
| Analysis Population Description |
|---|
| TP53-WT Population. The number analyzed includes participants who were evaluable at each timepoint. |
| Arm/Group Title | Placebo Plus Cytarabine | Idasanutlin Plus Cytarabine |
|---|---|---|
| Arm/Group Description | Participants received induction therapy idasanutlin matching placebo and cytarabine for 5 Days followed by 23 days of rest in Cycle 1 (treatment cycle length=28 days). Responding participants may continue with consolidation therapy for a maximum of 2 additional cycles including idasanutlin matching placebo and cytarabine for 5 days followed by 23 days of rest in each cycle (treatment cycle length=28 days). After each cycle, for participants achieving CRp or CRi, up to 28 additional days are allowed for blood count recovery, if needed. | Participants received induction therapy idasanutlin and cytarabine for 5 days followed by 23 days of rest in Cycle 1 (treatment cycle length=28 days). Responding participants may continue with consolidation therapy for a maximum of 2 additional cycles including idasanutlin and cytarabine for 5 days followed by 23 days of rest in each cycle (treatment cycle length=28 days). After each cycle, for participants achieving CRp or complete remission with incomplete blood count recovery (CRi), up to 28 additional days are allowed for blood count recovery, if needed. |
| Measure Participants | 25 | 59 |
| Median (95% Confidence Interval) [Months] |
18.73
|
16.76
|
| Title | Percentage of Participants Undergoing HSCT Following Complete Response (CR), in TP53 WT Population |
|---|---|
| Description | Rate of complete response at the end of induction in mutation-defined subgroups (positive for mutation of FLT3, IDH1 and IDH2, respectively) of the TP53 WT population was compared in participants who had been randomized to idasanutlin in combination with cytarabine versus those who had been randomized to cytarabine and placebo. The study was terminated because of futility, therefore did not reach the planned end of the study. |
| Time Frame | Baseline up to approximately 4.5 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| TP53-WT ITT Population |
| Arm/Group Title | Placebo Plus Cytarabine | Idasanutlin Plus Cytarabine |
|---|---|---|
| Arm/Group Description | Participants received induction therapy idasanutlin matching placebo and cytarabine for 5 Days followed by 23 days of rest in Cycle 1 (treatment cycle length=28 days). Responding participants may continue with consolidation therapy for a maximum of 2 additional cycles including idasanutlin matching placebo and cytarabine for 5 days followed by 23 days of rest in each cycle (treatment cycle length=28 days). After each cycle, for participants achieving CRp or CRi, up to 28 additional days are allowed for blood count recovery, if needed. | Participants received induction therapy idasanutlin and cytarabine for 5 days followed by 23 days of rest in Cycle 1 (treatment cycle length=28 days). Responding participants may continue with consolidation therapy for a maximum of 2 additional cycles including idasanutlin and cytarabine for 5 days followed by 23 days of rest in each cycle (treatment cycle length=28 days). After each cycle, for participants achieving CRp or complete remission with incomplete blood count recovery (CRi), up to 28 additional days are allowed for blood count recovery, if needed. |
| Measure Participants | 123 | 232 |
| Number [Percentage of Participants] |
10.6
7.1%
|
11.6
3.9%
|
| Title | Percentage of Participants With Complete Response (CR) in Clinically Actionable Mutation-Defined Subpopulation (FLT3, IDH1 and IDH2) in TP53 WT Population |
|---|---|
| Description | Rate of complete response at the end of induction in mutation-defined subgroups (positive for mutation of FLT3, IDH1 and IDH2, respectively) of the TP53 WT population was compared in participants who had been randomized to idasanutlin in combination with cytarabine versus those who had been randomized to cytarabine and placebo. |
| Time Frame | At the end of induction (up to Day 56) |
Outcome Measure Data
| Analysis Population Description |
|---|
| TP53-WT Population. The number analyzed includes participants who were evaluable at each timepoint. |
| Arm/Group Title | Placebo Plus Cytarabine | Idasanutlin Plus Cytarabine |
|---|---|---|
| Arm/Group Description | Participants received induction therapy idasanutlin matching placebo and cytarabine for 5 Days followed by 23 days of rest in Cycle 1 (treatment cycle length=28 days). Responding participants may continue with consolidation therapy for a maximum of 2 additional cycles including idasanutlin matching placebo and cytarabine for 5 days followed by 23 days of rest in each cycle (treatment cycle length=28 days). After each cycle, for participants achieving CRp or CRi, up to 28 additional days are allowed for blood count recovery, if needed. | Participants received induction therapy idasanutlin and cytarabine for 5 days followed by 23 days of rest in Cycle 1 (treatment cycle length=28 days). Responding participants may continue with consolidation therapy for a maximum of 2 additional cycles including idasanutlin and cytarabine for 5 days followed by 23 days of rest in each cycle (treatment cycle length=28 days). After each cycle, for participants achieving CRp or complete remission with incomplete blood count recovery (CRi), up to 28 additional days are allowed for blood count recovery, if needed. |
| Measure Participants | 123 | 232 |
| FLT3 |
12.5
8.4%
|
15.3
5.1%
|
| IDH1 |
11.1
7.4%
|
34.8
11.7%
|
| IDH2 |
23.1
15.5%
|
29.5
9.9%
|
| Title | Overall Survival in Clinically Actionable Mutation-Defined Subpopulation (FLT3, IDH1 and IDH2) in TP53 WT Population |
|---|---|
| Description | Overall survival in mutation-defined subgroups (positive for mutation of FLT3, IDH1 and IDH2 respectively) of the TP53 WT population was compared in participants who had been randomized to idasanutlin in combination with cytarabine versus those who had been randomized to cytarabine and placebo. The Median upper limits were set to 999 because they were not reached and therefore it was Not Evaluable (NE) and the field is numeric only. The study was terminated because of futility, therefore did not reach the planned end of the study. |
| Time Frame | From randomization to death from any cause (up to approximately 4.5 years) |
Outcome Measure Data
| Analysis Population Description |
|---|
| TP53-WT ITT Population. The number analyzed includes participants who were evaluable at each timepoint. |
| Arm/Group Title | Placebo Plus Cytarabine | Idasanutlin Plus Cytarabine |
|---|---|---|
| Arm/Group Description | Participants received induction therapy idasanutlin matching placebo and cytarabine for 5 Days followed by 23 days of rest in Cycle 1 (treatment cycle length=28 days). Responding participants may continue with consolidation therapy for a maximum of 2 additional cycles including idasanutlin matching placebo and cytarabine for 5 days followed by 23 days of rest in each cycle (treatment cycle length=28 days). After each cycle, for participants achieving CRp or CRi, up to 28 additional days are allowed for blood count recovery, if needed. | Participants received induction therapy idasanutlin and cytarabine for 5 days followed by 23 days of rest in Cycle 1 (treatment cycle length=28 days). Responding participants may continue with consolidation therapy for a maximum of 2 additional cycles including idasanutlin and cytarabine for 5 days followed by 23 days of rest in each cycle (treatment cycle length=28 days). After each cycle, for participants achieving CRp or complete remission with incomplete blood count recovery (CRi), up to 28 additional days are allowed for blood count recovery, if needed. |
| Measure Participants | 123 | 232 |
| IDH2 |
11.37
|
11.01
|
| IDH1 |
9.13
|
8.25
|
| FLT3 |
4.76
|
5.55
|
| Title | Number of Participants Who Experienced at Least One Adverse Event by Severity, According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.03 (NCI-CTCAE v4.03) |
|---|---|
| Description | Participants who experienced at least one Adverse Event by severity, According to National Cancer Institute common terminology criteria for Adverse Events, version 4.03 (NCI-CTCAE v4.03) have been reported. The study was terminated because of futility, therefore did not reach the planned end of the study. |
| Time Frame | Baseline up to approximately 4.5 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety-Evaluable Population |
| Arm/Group Title | Placebo Plus Cytarabine | Idasanutlin Plus Cytarabine |
|---|---|---|
| Arm/Group Description | Participants received induction therapy idasanutlin matching placebo and cytarabine for 5 Days followed by 23 days of rest in Cycle 1 (treatment cycle length=28 days). Responding participants may continue with consolidation therapy for a maximum of 2 additional cycles including idasanutlin matching placebo and cytarabine for 5 days followed by 23 days of rest in each cycle (treatment cycle length=28 days). After each cycle, for participants achieving CRp or CRi, up to 28 additional days are allowed for blood count recovery, if needed. | Participants received induction therapy idasanutlin and cytarabine for 5 days followed by 23 days of rest in Cycle 1 (treatment cycle length=28 days). Responding participants may continue with consolidation therapy for a maximum of 2 additional cycles including idasanutlin and cytarabine for 5 days followed by 23 days of rest in each cycle (treatment cycle length=28 days). After each cycle, for participants achieving CRp or complete remission with incomplete blood count recovery (CRi), up to 28 additional days are allowed for blood count recovery, if needed. |
| Measure Participants | 149 | 292 |
| Number [Participants] |
149
100%
|
232
77.9%
|
| Title | Number of Participants With Adverse Events Leading to Discontinuation |
|---|---|
| Description | Participants with Adverse Events leading to discontinuation of the study have been reported. The study was terminated because of futility, therefore did not reach the planned end of the study. |
| Time Frame | Baseline up to approximately 4.5 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Population |
| Arm/Group Title | Placebo Plus Cytarabine | Idasanutlin Plus Cytarabine |
|---|---|---|
| Arm/Group Description | Participants received induction therapy idasanutlin matching placebo and cytarabine for 5 Days followed by 23 days of rest in Cycle 1 (treatment cycle length=28 days). Responding participants may continue with consolidation therapy for a maximum of 2 additional cycles including idasanutlin matching placebo and cytarabine for 5 days followed by 23 days of rest in each cycle (treatment cycle length=28 days). After each cycle, for participants achieving CRp or CRi, up to 28 additional days are allowed for blood count recovery, if needed. | Participants received induction therapy idasanutlin and cytarabine for 5 days followed by 23 days of rest in Cycle 1 (treatment cycle length=28 days). Responding participants may continue with consolidation therapy for a maximum of 2 additional cycles including idasanutlin and cytarabine for 5 days followed by 23 days of rest in each cycle (treatment cycle length=28 days). After each cycle, for participants achieving CRp or complete remission with incomplete blood count recovery (CRi), up to 28 additional days are allowed for blood count recovery, if needed. |
| Measure Participants | 149 | 292 |
| Number [Participants] |
0
0%
|
0
0%
|
| Title | Number of Participants With Adverse Events Leading to Death up to Day 30 |
|---|---|
| Description | The number of participants with AE resulted by death within 30 days from dosing is reported |
| Time Frame | Up to Day 30 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Population |
| Arm/Group Title | Placebo Plus Cytarabine | Idasanutlin Plus Cytarabine |
|---|---|---|
| Arm/Group Description | Participants received induction therapy idasanutlin matching placebo and cytarabine for 5 Days followed by 23 days of rest in Cycle 1 (treatment cycle length=28 days). Responding participants may continue with consolidation therapy for a maximum of 2 additional cycles including idasanutlin matching placebo and cytarabine for 5 days followed by 23 days of rest in each cycle (treatment cycle length=28 days). After each cycle, for participants achieving CRp or CRi, up to 28 additional days are allowed for blood count recovery, if needed. | Participants received induction therapy idasanutlin and cytarabine for 5 days followed by 23 days of rest in Cycle 1 (treatment cycle length=28 days). Responding participants may continue with consolidation therapy for a maximum of 2 additional cycles including idasanutlin and cytarabine for 5 days followed by 23 days of rest in each cycle (treatment cycle length=28 days). After each cycle, for participants achieving CRp or complete remission with incomplete blood count recovery (CRi), up to 28 additional days are allowed for blood count recovery, if needed. |
| Measure Participants | 149 | 292 |
| Number [Participants] |
9
6%
|
23
7.7%
|
| Title | Number of Participants With Adverse Events Leading to Death up to Day 60 |
|---|---|
| Description | The number of participants with AE resulted by death within 60 days from dosing is reported |
| Time Frame | Up to Day 60 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Population |
| Arm/Group Title | Placebo Plus Cytarabine | Idasanutlin Plus Cytarabine |
|---|---|---|
| Arm/Group Description | Participants received induction therapy idasanutlin matching placebo and cytarabine for 5 Days followed by 23 days of rest in Cycle 1 (treatment cycle length=28 days). Responding participants may continue with consolidation therapy for a maximum of 2 additional cycles including idasanutlin matching placebo and cytarabine for 5 days followed by 23 days of rest in each cycle (treatment cycle length=28 days). After each cycle, for participants achieving CRp or CRi, up to 28 additional days are allowed for blood count recovery, if needed. | Participants received induction therapy idasanutlin and cytarabine for 5 days followed by 23 days of rest in Cycle 1 (treatment cycle length=28 days). Responding participants may continue with consolidation therapy for a maximum of 2 additional cycles including idasanutlin and cytarabine for 5 days followed by 23 days of rest in each cycle (treatment cycle length=28 days). After each cycle, for participants achieving CRp or complete remission with incomplete blood count recovery (CRi), up to 28 additional days are allowed for blood count recovery, if needed. |
| Measure Participants | 149 | 292 |
| Number [Participants] |
24
16.1%
|
60
20.1%
|
| Title | Number of Participants With Clinical Laboratory Abnormalities in Biochemistry Tests at the Greatest Severity, According to NCI-CTCAE v4.03 |
|---|---|
| Description | Laboratory parameters for blood biochemistry will be measured and compared with a standard reference range. Values outside the standard reference range are considered abnormalities. A laboratory test result will be reported as an adverse event if it meets any of the following criteria: is accompanied by clinical symptoms; results in a change in study treatment or a medical intervention; or is clinically significant in the investigator's judgment. For each patient, baseline is the last observation prior to initiation of study drug. For each laboratory test, patients with at least 1 post-baseline assessment are included in the analysis. For each cell, the denominator is the number of patients with baseline NCI-CTCAE Grade 0-2 in the specified direction of abnormality, or Grade 1-4 in the opposite direction of abnormality. |
| Time Frame | Up to Approximately 4.5 Years |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Population. The number analyzed includes participants who were evaluable at each timepoint. |
| Arm/Group Title | Placebo Plus Cytarabine | Idasanutlin Plus Cytarabine |
|---|---|---|
| Arm/Group Description | Participants received induction therapy idasanutlin matching placebo and cytarabine for 5 Days followed by 23 days of rest in Cycle 1 (treatment cycle length=28 days). Responding participants may continue with consolidation therapy for a maximum of 2 additional cycles including idasanutlin matching placebo and cytarabine for 5 days followed by 23 days of rest in each cycle (treatment cycle length=28 days). After each cycle, for participants achieving CRp or CRi, up to 28 additional days are allowed for blood count recovery, if needed. | Participants received induction therapy idasanutlin and cytarabine for 5 days followed by 23 days of rest in Cycle 1 (treatment cycle length=28 days). Responding participants may continue with consolidation therapy for a maximum of 2 additional cycles including idasanutlin and cytarabine for 5 days followed by 23 days of rest in each cycle (treatment cycle length=28 days). After each cycle, for participants achieving CRp or complete remission with incomplete blood count recovery (CRi), up to 28 additional days are allowed for blood count recovery, if needed. |
| Measure Participants | 149 | 292 |
| Albumin Low |
8
5.4%
|
22
7.4%
|
| Alkaline Phosphatase High |
2
1.3%
|
9
3%
|
| SGPT/ALT High |
13
8.7%
|
16
5.4%
|
| SGOT/AST High |
9
6%
|
13
4.4%
|
| Calcium Low |
8
5.4%
|
36
12.1%
|
| Creatinine High |
4
2.7%
|
11
3.7%
|
| Glucose Low |
1
0.7%
|
0
0%
|
| Glucose High |
9
6%
|
25
8.4%
|
| Magnesium Low |
0
0%
|
8
2.7%
|
| Magnesium High |
5
3.4%
|
10
3.4%
|
| Phosphorus Low |
18
12.1%
|
72
24.2%
|
| Potassium High |
5
3.4%
|
8
2.7%
|
| Sodium Low |
6
4%
|
17
5.7%
|
| Sodium High |
1
0.7%
|
7
2.3%
|
| Bilirubin High |
9
6%
|
42
14.1%
|
| Uric Acid High |
29
19.5%
|
53
17.8%
|
| Potassium Low |
21
14.1%
|
76
25.5%
|
| Title | Number of Participants With Clinical Laboratory Abnormalities in Hematology Tests at the Greatest Severity, According to NCI-CTCAE v4.03 |
|---|---|
| Description | Laboratory parameters for hematology will be measured and compared with a standard reference range. Values outside the standard reference range are considered abnormalities. A laboratory test result will be reported as an adverse event if it meets any of the following criteria: is accompanied by clinical symptoms; results in a change in study treatment or a medical intervention; or is clinically significant in the investigator's judgment. For each patient, baseline is the last observation prior to initiation of study drug. For each laboratory test, patients with at least 1 post-baseline assessment are included in the analysis. For each cell, the denominator is the number of patients with baseline NCI-CTCAE Grade 0-2 in the specified direction of abnormality, or Grade 1-4 in the opposite direction of abnormality. |
| Time Frame | Up to Approximately 4.5 Years |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Population. The number analyzed includes participants who were evaluable at each timepoint. |
| Arm/Group Title | Placebo Plus Cytarabine | Idasanutlin Plus Cytarabine |
|---|---|---|
| Arm/Group Description | Participants received induction therapy idasanutlin matching placebo and cytarabine for 5 Days followed by 23 days of rest in Cycle 1 (treatment cycle length=28 days). Responding participants may continue with consolidation therapy for a maximum of 2 additional cycles including idasanutlin matching placebo and cytarabine for 5 days followed by 23 days of rest in each cycle (treatment cycle length=28 days). After each cycle, for participants achieving CRp or CRi, up to 28 additional days are allowed for blood count recovery, if needed. | Participants received induction therapy idasanutlin and cytarabine for 5 days followed by 23 days of rest in Cycle 1 (treatment cycle length=28 days). Responding participants may continue with consolidation therapy for a maximum of 2 additional cycles including idasanutlin and cytarabine for 5 days followed by 23 days of rest in each cycle (treatment cycle length=28 days). After each cycle, for participants achieving CRp or complete remission with incomplete blood count recovery (CRi), up to 28 additional days are allowed for blood count recovery, if needed. |
| Measure Participants | 149 | 292 |
| Hemoglobin Low |
83
55.7%
|
191
64.1%
|
| Hemoglobin High |
1
0.7%
|
1
0.3%
|
| Lymphocytes Abs Low |
109
73.2%
|
229
76.8%
|
| Lymphocytes Abs High |
1
0.7%
|
1
0.3%
|
| Neutrophils, Total, Abs Low |
40
26.8%
|
97
32.6%
|
| Platelet Low |
59
39.6%
|
128
43%
|
| Total Leukocyte Count Low |
87
58.4%
|
184
61.7%
|
| Total Leukocyte Count High |
1
0.7%
|
1
0.3%
|
| Title | Change From Baseline in Body Temperature Over Time |
|---|---|
| Description | Vital signs were measured prior to the infusion while the participant was in a seated position. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. The study was terminated because of futility, therefore did not reach the planned end of study. |
| Time Frame | Baseline; Cycles 1-3, Days 8, 15, 22, 28 (1 cycle is 28 days); and, if incomplete blood count recovery, Days 29-42 and Days 43-56, Cycles 2 -3 Days 1, 8, 15, 22, 28 and 29-56 (max delay between cycles is 56 days) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Population. The number analyzed includes participants who were evaluable at each timepoint. |
| Arm/Group Title | Placebo Plus Cytarabine | Idasanutlin Plus Cytarabine |
|---|---|---|
| Arm/Group Description | Participants received induction therapy idasanutlin matching placebo and cytarabine for 5 Days followed by 23 days of rest in Cycle 1 (treatment cycle length=28 days). Responding participants may continue with consolidation therapy for a maximum of 2 additional cycles including idasanutlin matching placebo and cytarabine for 5 days followed by 23 days of rest in each cycle (treatment cycle length=28 days). After each cycle, for participants achieving CRp or CRi, up to 28 additional days are allowed for blood count recovery, if needed. | Participants received induction therapy idasanutlin and cytarabine for 5 days followed by 23 days of rest in Cycle 1 (treatment cycle length=28 days). Responding participants may continue with consolidation therapy for a maximum of 2 additional cycles including idasanutlin and cytarabine for 5 days followed by 23 days of rest in each cycle (treatment cycle length=28 days). After each cycle, for participants achieving CRp or complete remission with incomplete blood count recovery (CRi), up to 28 additional days are allowed for blood count recovery, if needed. |
| Measure Participants | 149 | 292 |
| Baseline |
36.49
(0.59)
|
36.52
(0.51)
|
| Cycle 1 Day 8 |
0.07
(0.82)
|
0.32
(0.72)
|
| Cycle 1 Day 15 |
0.30
(0.91)
|
0.46
(0.92)
|
| Cycle 1 Day 22 |
0.22
(0.74)
|
0.36
(0.86)
|
| Cycle 1 Day 28 |
0.06
(0.65)
|
0.23
(0.87)
|
| Cycle 1 Day 29-42 |
0.08
(0.69)
|
0.00
(0.71)
|
| Cycle 1 Day 43-56 |
-0.02
(0.53)
|
0.07
(0.80)
|
| Cycle 2 Day 1 |
0.11
(0.60)
|
-0.10
(0.47)
|
| Cycle 2 Day 8 |
-0.08
(0.51)
|
0.07
(0.56)
|
| Cycle 2 Day 15 |
0.17
(0.76)
|
0.34
(0.83)
|
| Cycle 2 Day 22 |
0.04
(0.72)
|
0.10
(0.59)
|
| Cycle 2 Day 28 |
-0.22
(0.65)
|
0.04
(0.62)
|
| Cycle 2 Day 29-56 |
-0.06
(0.36)
|
-0.09
(0.55)
|
| Cycle 3 Day 1 |
-0.25
(0.54)
|
-0.19
(0.51)
|
| Cycle 3 Day 8 |
0.10
(0.60)
|
-0.04
(0.59)
|
| Cycle 3 Day 15 |
-0.09
(0.76)
|
0.29
(0.65)
|
| Cycle 3 Day 22 |
-0.07
(0.64)
|
0.04
(0.49)
|
| Cycle 3 Day 28 |
-0.26
(0.63)
|
-0.15
(0.52)
|
| Cycle 3 Day 29-56 |
0.27
(0.47)
|
-0.25
(0.52)
|
| Title | Change From Baseline in Systolic Blood Pressure Over Time |
|---|---|
| Description | Vital signs were measured prior to the infusion while the participant was in a seated position. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. The study was terminated because of futility, therefore did not reach the planned end of study. |
| Time Frame | Baseline; Cycles 1-3, Days 8, 15, 22, 28 (1 cycle is 28 days); and, if incomplete blood count recovery, Days 29-42 and Days 43-56, Cycles 2 -3 Days 1, 8, 15, 22, 28 and 29-56 (max delay between cycles is 56 days) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Population. The number analyzed includes participants who were evaluable at each timepoint. |
| Arm/Group Title | Placebo Plus Cytarabine | Idasanutlin Plus Cytarabine |
|---|---|---|
| Arm/Group Description | Participants received induction therapy idasanutlin matching placebo and cytarabine for 5 Days followed by 23 days of rest in Cycle 1 (treatment cycle length=28 days). Responding participants may continue with consolidation therapy for a maximum of 2 additional cycles including idasanutlin matching placebo and cytarabine for 5 days followed by 23 days of rest in each cycle (treatment cycle length=28 days). After each cycle, for participants achieving CRp or CRi, up to 28 additional days are allowed for blood count recovery, if needed. | Participants received induction therapy idasanutlin and cytarabine for 5 days followed by 23 days of rest in Cycle 1 (treatment cycle length=28 days). Responding participants may continue with consolidation therapy for a maximum of 2 additional cycles including idasanutlin and cytarabine for 5 days followed by 23 days of rest in each cycle (treatment cycle length=28 days). After each cycle, for participants achieving CRp or complete remission with incomplete blood count recovery (CRi), up to 28 additional days are allowed for blood count recovery, if needed. |
| Measure Participants | 149 | 292 |
| Baseline |
120.6
(17.2)
|
122.1
(16.2)
|
| Cycle 1 Day 8 |
-3.7
(20.0)
|
-6.9
(18.6)
|
| Cycle 1 Day 15 |
-2.8
(19.2)
|
-0.1
(18.7)
|
| Cycle 1 Day 22 |
0.7
(20.3)
|
-1.5
(19.6)
|
| Cycle 1 Day 28 |
1.2
(21.7)
|
-0.5
(17.6)
|
| Cycle 1 Day 29-42 |
4.4
(17.8)
|
3.4
(17.7)
|
| Cycle 1 Day 43-56 |
9.8
(17.4)
|
3.8
(20.9)
|
| Cycle 2 Day 1 |
6.9
(15.6)
|
0.6
(15.2)
|
| Cycle 2 Day 8 |
5.3
(18.6)
|
-5.1
(16.2)
|
| Cycle 2 Day 15 |
-1.7
(17.7)
|
-0.2
(19.6)
|
| Cycle 2 Day 22 |
5.5
(19.8)
|
2.5
(17.0)
|
| Cycle 2 Day 28 |
5.8
(22.2)
|
5.0
(17.9)
|
| Cycle 2 Day 29-56 |
-1.0
(18.2)
|
6.6
(16.3)
|
| Cycle 3 Day 1 |
11.2
(18.9)
|
2.3
(18.2)
|
| Cycle 3 Day 8 |
6.0
(23.5)
|
-1.7
(13.4)
|
| Cycle 3 Day 15 |
3.3
(22.5)
|
0.2
(21.7)
|
| Cycle 3 Day 22 |
13.9
(22.8)
|
-1.1
(17.7)
|
| Cycle 3 Day 28 |
5.3
(23.0)
|
7.1
(18.0)
|
| Cycle 3 Day 29-56 |
27.7
(28.3)
|
5.1
(18.4)
|
| Title | Change From Baseline in Diastolic Blood Pressure Over Time |
|---|---|
| Description | Vital signs were measured prior to the infusion while the participant was in a seated position. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. The study was terminated because of futility, therefore did not reach the planned end of study. |
| Time Frame | Baseline; Cycles 1-3, Days 8, 15, 22, 28 (1 cycle is 28 days); and, if incomplete blood count recovery, Days 29-42 and Days 43-56, Cycles 2 -3 Days 1, 8, 15, 22, 28 and 29-56 (max delay between cycles is 56 days) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Population. The number analyzed includes participants who were evaluable at each timepoint. |
| Arm/Group Title | Placebo Plus Cytarabine | Idasanutlin Plus Cytarabine |
|---|---|---|
| Arm/Group Description | Participants received induction therapy idasanutlin matching placebo and cytarabine for 5 Days followed by 23 days of rest in Cycle 1 (treatment cycle length=28 days). Responding participants may continue with consolidation therapy for a maximum of 2 additional cycles including idasanutlin matching placebo and cytarabine for 5 days followed by 23 days of rest in each cycle (treatment cycle length=28 days). After each cycle, for participants achieving CRp or CRi, up to 28 additional days are allowed for blood count recovery, if needed. | Participants received induction therapy idasanutlin and cytarabine for 5 days followed by 23 days of rest in Cycle 1 (treatment cycle length=28 days). Responding participants may continue with consolidation therapy for a maximum of 2 additional cycles including idasanutlin and cytarabine for 5 days followed by 23 days of rest in each cycle (treatment cycle length=28 days). After each cycle, for participants achieving CRp or complete remission with incomplete blood count recovery (CRi), up to 28 additional days are allowed for blood count recovery, if needed. |
| Measure Participants | 149 | 292 |
| Baseline |
70.2
(9.9)
|
71.5
(10.6)
|
| Cycle 1 Day 8 |
-1.5
(12.6)
|
-3.1
(12.7)
|
| Cycle 1 Day 15 |
-1.3
(11.3)
|
-1.3
(12.3)
|
| Cycle 1 Day 22 |
-0.5
(11.1)
|
-1.4
(12.9)
|
| Cycle 1 Day 28 |
1.0
(13.2)
|
-0.7
(12.6)
|
| Cycle 1 Day 29-42 |
3.8
(10.5)
|
0.6
(12.4)
|
| Cycle 1 Day 43-56 |
1.7
(11.8)
|
0.9
(13.5)
|
| Cycle 2 Day 1 |
1.1
(13.5)
|
0.9
(12.9)
|
| Cycle 2 Day 8 |
0.4
(13.5)
|
-2.2
(13.2)
|
| Cycle 2 Day 15 |
-0.6
(14.8)
|
-1.5
(15.4)
|
| Cycle 2 Day 22 |
3.1
(11.6)
|
1.7
(11.3)
|
| Cycle 2 Day 28 |
4.6
(13.9)
|
3.9
(12.7)
|
| Cycle 2 Day 29-56 |
-2.9
(12.4)
|
3.2
(15.8)
|
| Cycle 3 Day 1 |
5.0
(8.4)
|
0.3
(10.7)
|
| Cycle 3 Day 8 |
2.0
(15.5)
|
-3.3
(11.8)
|
| Cycle 3 Day 15 |
0.7
(11.1)
|
-1.8
(11.1)
|
| Cycle 3 Day 22 |
10.1
(14.3)
|
-2.1
(9.3)
|
| Cycle 3 Day 28 |
2.3
(14.7)
|
1.3
(10.1)
|
| Cycle 3 Day 29-56 |
5.0
(21.8)
|
2.6
(13.6)
|
| Title | Change From Baseline in Pulse Rate Over Time |
|---|---|
| Description | Vital signs were measured prior to the infusion while the participant was in a seated position. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. The study was terminated because of futility, therefore did not reach the planned end of study. |
| Time Frame | Baseline; Cycles 1-3, Days 8, 15, 22, 28 (1 cycle is 28 days); and, if incomplete blood count recovery, Days 29-42 and Days 43-56, Cycles 2 -3 Days 1, 8, 15, 22, 28 and 29-56 (max delay between cycles is 56 days) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Population. The number analyzed includes participants who were evaluable at each timepoint. |
| Arm/Group Title | Placebo Plus Cytarabine | Idasanutlin Plus Cytarabine |
|---|---|---|
| Arm/Group Description | Participants received induction therapy idasanutlin matching placebo and cytarabine for 5 Days followed by 23 days of rest in Cycle 1 (treatment cycle length=28 days). Responding participants may continue with consolidation therapy for a maximum of 2 additional cycles including idasanutlin matching placebo and cytarabine for 5 days followed by 23 days of rest in each cycle (treatment cycle length=28 days). After each cycle, for participants achieving CRp or CRi, up to 28 additional days are allowed for blood count recovery, if needed. | Participants received induction therapy idasanutlin and cytarabine for 5 days followed by 23 days of rest in Cycle 1 (treatment cycle length=28 days). Responding participants may continue with consolidation therapy for a maximum of 2 additional cycles including idasanutlin and cytarabine for 5 days followed by 23 days of rest in each cycle (treatment cycle length=28 days). After each cycle, for participants achieving CRp or complete remission with incomplete blood count recovery (CRi), up to 28 additional days are allowed for blood count recovery, if needed. |
| Measure Participants | 149 | 292 |
| Baseline |
78.4
(14.4)
|
79.2
(12.9)
|
| Cycle 1 Day 8 |
-4.3
(15.9)
|
3.4
(15.6)
|
| Cycle 1 Day 15 |
1.5
(16.0)
|
1.1
(17.2)
|
| Cycle 1 Day 22 |
0.2
(16.2)
|
4.1
(15.8)
|
| Cycle 1 Day 28 |
4.8
(15.8)
|
4.0
(16.8)
|
| Cycle 1 Day 29-42 |
2.0
(13.5)
|
5.1
(16.4)
|
| Cycle 1 Day 43-56 |
5.5
(18.6)
|
6.8
(14.0)
|
| Cycle 2 Day 1 |
2.0
(16.6)
|
-0.9
(12.0)
|
| Cycle 2 Day 8 |
-3.3
(18.6)
|
2.4
(14.9)
|
| Cycle 2 Day 15 |
-0.4
(12.7)
|
1.7
(18.4)
|
| Cycle 2 Day 22 |
2.3
(15.5)
|
0.3
(15.4)
|
| Cycle 2 Day 28 |
-2.3
(14.6)
|
1.2
(12.2)
|
| Cycle 2 Day 29-56 |
1.8
(11.8)
|
4.0
(14.8)
|
| Cycle 3 Day 1 |
0.4
(18.4)
|
1.0
(9.8)
|
| Cycle 3 Day 8 |
1.3
(21.5)
|
2.4
(16.2)
|
| Cycle 3 Day 15 |
2.5
(16.9)
|
1.9
(11.9)
|
| Cycle 3 Day 22 |
4.8
(19.7)
|
3.4
(13.6)
|
| Cycle 3 Day 28 |
0.4
(16.1)
|
0.9
(13.7)
|
| Cycle 3 Day 29-56 |
-5.0
(1.7)
|
5.2
(11.5)
|
| Title | Change From Baseline in Respiratory Rate Over Time |
|---|---|
| Description | Vital signs were measured prior to the infusion while the participant was in a seated position. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. The study was terminated because of futility, therefore did not reach the planned end of study. |
| Time Frame | Up to Approximately 4.5 Years |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Population. The number analyzed includes participants who were evaluable at each timepoint. |
| Arm/Group Title | Placebo Plus Cytarabine | Idasanutlin Plus Cytarabine |
|---|---|---|
| Arm/Group Description | Participants received induction therapy idasanutlin matching placebo and cytarabine for 5 Days followed by 23 days of rest in Cycle 1 (treatment cycle length=28 days). Responding participants may continue with consolidation therapy for a maximum of 2 additional cycles including idasanutlin matching placebo and cytarabine for 5 days followed by 23 days of rest in each cycle (treatment cycle length=28 days). After each cycle, for participants achieving CRp or CRi, up to 28 additional days are allowed for blood count recovery, if needed. | Participants received induction therapy idasanutlin and cytarabine for 5 days followed by 23 days of rest in Cycle 1 (treatment cycle length=28 days). Responding participants may continue with consolidation therapy for a maximum of 2 additional cycles including idasanutlin and cytarabine for 5 days followed by 23 days of rest in each cycle (treatment cycle length=28 days). After each cycle, for participants achieving CRp or complete remission with incomplete blood count recovery (CRi), up to 28 additional days are allowed for blood count recovery, if needed. |
| Measure Participants | 149 | 292 |
| Baseline |
16.3
(2.7)
|
16.6
(2.7)
|
| Cycle 1 Day 8 |
-0.1
(2.7)
|
0.0
(2.8)
|
| Cycle 1 Day 15 |
0.7
(2.9)
|
0.4
(2.8)
|
| Cycle 1 Day 22 |
0.6
(3.2)
|
0.7
(4.1)
|
| Cycle 1 Day 28 |
0.4
(2.9)
|
0.6
(2.9)
|
| Cycle 1 Day 29-42 |
0.7
(2.1)
|
0.5
(2.7)
|
| Cycle 1 Day 43-56 |
0.3
(1.0)
|
0.0
(2.9)
|
| Cycle 2 Day 1 |
-0.3
(2.8)
|
-0.2
(3.2)
|
| Cycle 2 Day 8 |
-0.2
(2.9)
|
0.1
(3.3)
|
| Cycle 2 Day 15 |
0.5
(2.4)
|
0.0
(2.5)
|
| Cycle 2 Day 22 |
0.8
(2.3)
|
0.4
(1.4)
|
| Cycle 2 Day 28 |
-0.3
(2.3)
|
0.5
(3.5)
|
| Cycle 2 Day 29-56 |
0.2
(1.8)
|
0.3
(2.5)
|
| Cycle 3 Day 1 |
1.1
(2.5)
|
0.2
(2.1)
|
| Cycle 3 Day 8 |
0.2
(2.5)
|
-1.0
(3.1)
|
| Cycle 3 Day 15 |
1.5
(3.6)
|
0.9
(2.2)
|
| Cycle 3 Day 22 |
1.1
(2.7)
|
0.8
(1.6)
|
| Cycle 3 Day 28 |
0.3
(1.2)
|
0.8
(1.8)
|
| Cycle 3 Day 29-56 |
0.7
(4.6)
|
0.1
(2.4)
|
| Title | Change From Baseline in Heart Rate, as Measured by Electrocardiogram |
|---|---|
| Description | Single 12-lead ECGs was obtained using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and QTc intervals. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. The study was terminated because of futility, therefore did not reach the planned end of study. |
| Time Frame | Baseline; Cycles 1-3 Day 1 (2 hrs pre-dose, post-Cytarabine and 6 hrs post-Idasanutlin/Placebo ); Cycle 1-3 Day 2; Cycle 1 Day 5 (within 2 hrs Idanasanutlin/Placebo, post-Cytarabine and 6 hrs post-Idasanutlin/Placebo), Study Drug Completion |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Population. The number analyzed includes participants who were evaluable at each timepoint. |
| Arm/Group Title | Placebo Plus Cytarabine | Idasanutlin Plus Cytarabine |
|---|---|---|
| Arm/Group Description | Participants received induction therapy idasanutlin matching placebo and cytarabine for 5 Days followed by 23 days of rest in Cycle 1 (treatment cycle length=28 days). Responding participants may continue with consolidation therapy for a maximum of 2 additional cycles including idasanutlin matching placebo and cytarabine for 5 days followed by 23 days of rest in each cycle (treatment cycle length=28 days). After each cycle, for participants achieving CRp or CRi, up to 28 additional days are allowed for blood count recovery, if needed. | Participants received induction therapy idasanutlin and cytarabine for 5 days followed by 23 days of rest in Cycle 1 (treatment cycle length=28 days). Responding participants may continue with consolidation therapy for a maximum of 2 additional cycles including idasanutlin and cytarabine for 5 days followed by 23 days of rest in each cycle (treatment cycle length=28 days). After each cycle, for participants achieving CRp or complete remission with incomplete blood count recovery (CRi), up to 28 additional days are allowed for blood count recovery, if needed. |
| Measure Participants | 149 | 292 |
| Baseline |
77.3
(13.2)
|
78.6
(14.2)
|
| Cycle 1 Day 1 2 Hours Pre-dose |
1.1
(11.6)
|
-0.8
(11.7)
|
| Cycle 1 Day 1 Post-Cytarabine |
-0.1
(8.4)
|
-0.4
(9.8)
|
| Cycle 1 Day 1 6 Hours Post-Idasanutlin/Placebo |
0.1
(9.6)
|
1.4
(9.2)
|
| Cycle 1 Day 2 |
-2.2
(11.0)
|
-0.4
(11.7)
|
| Cycle 1 Day 5 Within 2 Hours Pre-Idasanutlin/Placebo |
-10.3
(14.4)
|
-1.2
(14.3)
|
| Cycle 1 Day 5 - Post-Cytarabine |
-9.9
(12.8)
|
-3.0
(14.2)
|
| Cycle 1 Day 5 6 Hours Post-Idasanutlin/Placebo |
-10.7
(13.2)
|
-3.1
(14.0)
|
| Cycle 2 Day 1 Within 2 Hours Pre-Idasanutlin/Placebo |
-0.5
(13.5)
|
-4.8
(12.0)
|
| Cycle 2 Day 1 Post-Cytarabine |
0.8
(17.3)
|
-4.8
(12.6)
|
| Cycle 2 Day 1 6 Hours Post-Idasanutlin/Placebo |
-0.7
(16.6)
|
-0.7
(15.6)
|
| Cycle 2 Day 2 |
-5.2
(15.7)
|
-4.8
(10.3)
|
| Cycle 3 Day 1 Within 2 Hours Pre-Idasanutlin/Placebo |
-3.0
(14.2)
|
-7.1
(10.2)
|
| Cycle 3 Day 1 Post-Cytarabine |
-8.9
(21.0)
|
-4.5
(7.4)
|
| Cycle 3 Day 1 6 Hours Post-Idasanutlin/Placebo |
-2.0
(17.2)
|
-0.1
(15.0)
|
| Cycle 3 Day 2 |
0.1
(14.7)
|
-9.3
(8.8)
|
| Study Drug Completion/Discontinuation |
3.4
(15.9)
|
4.5
(16.4)
|
| Title | Change From Baseline in Electrocardiogram Parameters: PQ, PR, RR, QRS, QT and QTcF Intervals |
|---|---|
| Description | Single 12-lead ECGs was obtained using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and QTc intervals. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. The study was terminated because of futility, therefore did not reach the planned end of study. |
| Time Frame | Baseline, Days 1, 2, and 5 of Cycle 1, Days 1, 2 of Cycles 2 and 3 (1 cycle is 28 days), Treatment Discontinuation Visit (28 days after last dose of study drug) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Population. The number analyzed includes participants who were evaluable at each timepoint. |
| Arm/Group Title | Placebo Plus Cytarabine | Idasanutlin Plus Cytarabine |
|---|---|---|
| Arm/Group Description | Participants received induction therapy idasanutlin matching placebo and cytarabine for 5 Days followed by 23 days of rest in Cycle 1 (treatment cycle length=28 days). Responding participants may continue with consolidation therapy for a maximum of 2 additional cycles including idasanutlin matching placebo and cytarabine for 5 days followed by 23 days of rest in each cycle (treatment cycle length=28 days). After each cycle, for participants achieving CRp or CRi, up to 28 additional days are allowed for blood count recovery, if needed. | Participants received induction therapy idasanutlin and cytarabine for 5 days followed by 23 days of rest in Cycle 1 (treatment cycle length=28 days). Responding participants may continue with consolidation therapy for a maximum of 2 additional cycles including idasanutlin and cytarabine for 5 days followed by 23 days of rest in each cycle (treatment cycle length=28 days). After each cycle, for participants achieving CRp or complete remission with incomplete blood count recovery (CRi), up to 28 additional days are allowed for blood count recovery, if needed. |
| Measure Participants | 149 | 292 |
| PR Duration Baseline |
160.3
(37.5)
|
155.5
(32.4)
|
| PR Duration Cycle 1 Day 1 Within 2 Hours Pre-Idasanutlin/Placebo |
12.4
(54.8)
|
-2.7
(52.6)
|
| PR Duration Cycle 1 Day 1 - Post-Cytarabine |
4.8
(40.9)
|
1.6
(30.4)
|
| PR Duration Cycle 1 Day 1 6 Hours Post-Idasanutlin/Placebo |
0.6
(46.0)
|
1.6
(28.4)
|
| PR Duration Cycle 1 Day 2 |
2.1
(28.8)
|
1.4
(25.8)
|
| PR Duration Cycle 1 Day 5 Within 2 Hours Pre-Idasanutlin/Placebo |
-3.0
(31.5)
|
-2.1
(25.0)
|
| PR Duration Cycle 1 Day 5 Post-Cytarabine |
1.2
(50.3)
|
-1.6
(18.3)
|
| PR Duration Cycle 1 Day 5 6 Hours Post-Idasanutlin/Placebo |
-5.7
(30.3)
|
-3.5
(24.6)
|
| PR Duration Cycle 2 Day 1 Within 2 Hours Pre-Idasanutlin/Placebo |
30.0
(75.9)
|
2.2
(17.6)
|
| PR Duration Cycle 2 Day 1 Post-Cytarabine |
-4.2
(15.2)
|
4.9
(11.7)
|
| PR Duration Cycle 2 Day 1 6 Hours Post-Idasanutlin/Placebo |
-3.0
(16.8)
|
6.0
(14.6)
|
| PR Duration Cycle 2 Day 2 |
-3.0
(18.7)
|
5.9
(12.3)
|
| PR Duration Cycle 3 Day 1 Within 2 Hours Pre-Idasanutlin/Placebo |
9.3
(28.6)
|
6.7
(11.7)
|
| PR Duration Cycle 3 Day 1 Post-Cytarabine |
-7.7
(5.3)
|
3.9
(10.0)
|
| PR Duration Cycle 3 Day 1 6 Hours Post-Idasanutlin/Placebo |
-4.5
(9.9)
|
6.9
(12.0)
|
| PR Duration Cycle 3 Day 2 |
-1.0
(3.3)
|
14.1
(12.9)
|
| PR Duration Study Drug Completion/Discontinuation |
-5.3
(28.6)
|
-7.7
(37.1)
|
| QRS Duration Baseline |
92.8
(17.7)
|
89.3
(16.5)
|
| QRS Duration Cycle 1 Day 1 Within 2 Hours Pre-Idasanutlin/Placebo |
-0.4
(3.2)
|
-1.9
(6.2)
|
| QRS Duration Cycle 1 Day 1 Post-Cytarabine |
-0.9
(10.0)
|
-1.0
(6.7)
|
| QRS Duration Cycle 1 Day 1 6 Hours Post-Idasanutlin/Placebo |
-0.6
(18.4)
|
-1.1
(6.9)
|
| QRS Duration Cycle 1 Day 2 |
-0.5
(11.6)
|
1.1
(7.8)
|
| QRS Duration Cycle 1 Day 5 Within 2 Hours Pre-Idasanutlin/Placebo |
1.1
(8.7)
|
1.6
(9.1)
|
| QRS Duration Cycle 1 Day 5 Post-Cytarabine |
0.6
(12.2)
|
0.2
(11.2)
|
| QRS Duration Cycle 1 Day 5 6 Hours Post-Idasanutlin/Placebo |
0.3
(13.0)
|
-0.3
(10.6)
|
| QRS Duration Cycle 2 Day 1 Within 2 Hours Pre-Idasanutlin/Placebo |
0.8
(4.7)
|
0.4
(8.0)
|
| QRS Duration Cycle 2 Day 1 Post-Cytarabine |
6.5
(12.2)
|
-2.1
(9.4)
|
| QRS Duration Cycle 2 Day 1 6 Hours Post-Idasanutlin/Placebo |
2.0
(13.9)
|
0.1
(6.6)
|
| QRS Duration Cycle 2 Day 2 |
0.3
(6.3)
|
0.2
(7.1)
|
| QRS Duration Cycle 3 Day 1 Within 2 Hours Pre-Idasanutlin/Placebo |
-0.1
(5.9)
|
-2.4
(5.9)
|
| QRS Duration Cycle 3 Day 1 Post-Cytarabine |
2.7
(5.3)
|
-2.0
(3.4)
|
| QRS Duration Cycle 3 Day 1 6 Hours Post-Idasanutlin/Placebo |
0.4
(5.4)
|
-2.7
(3.8)
|
| QRS Duration Cycle 3 Day 2 |
1.5
(6.6)
|
-1.6
(8.7)
|
| QRS Duration Study Drug Completion/Discontinuation |
-1.3
(10.1)
|
-0.4
(12.7)
|
| QT Duration Baseline |
388.7
(35.9)
|
385.6
(35.7)
|
| QT Duration Cycle 1 Day 1 Within 2 Hours Pre-Idasanutlin/Placebo |
6.0
(30.6)
|
4.2
(32.4)
|
| QT Duration Cycle 1 Day 1 Post-Cytarabine |
0.7
(25.3)
|
4.4
(24.2)
|
| QT Duration Cycle 1 Day 1 6 Hours Post-Idasanutlin/Placebo |
1.1
(28.2)
|
0.0
(25.4)
|
| QT Duration Cycle 1 Day 2 |
5.4
(31.9)
|
3.1
(31.7)
|
| QT Duration Cycle 1 Day 5 Within 2 Hours Pre-Idasanutlin/Placebo |
24.8
(44.6)
|
1.6
(35.5)
|
| QT Duration Cycle 1 Day 5 Post-Cytarabine |
25.0
(41.0)
|
4.7
(36.6)
|
| QT Duration Cycle 1 Day 5 6 Hours Post-Idasanutlin/Placebo |
27.8
(42.3)
|
3.4
(34.8)
|
| QT Duration Cycle 2 Day 1 Within 2 Hours Pre-Idasanutlin/Placebo |
-9.1
(34.8)
|
8.5
(31.3)
|
| QT Duration Cycle 2 Day 1 Post-Cytarabine |
-11.5
(29.2)
|
10.6
(31.3)
|
| QT Duration Cycle 2 Day 1 6 Hours Post-Idasanutlin/Placebo |
-7.5
(31.4)
|
4.1
(39.7)
|
| QT Duration Cycle 2 Day 2 |
12.2
(24.7)
|
9.9
(38.6)
|
| QT Duration Cycle 3 Day 1 Within 2 Hours Pre-Idasanutlin/Placebo |
1.9
(33.4)
|
15.9
(33.8)
|
| QT Duration Cycle 3 Day 1 Post-Cytarabine |
21.2
(33.2)
|
22.0
(35.3)
|
| QT Duration Cycle 3 Day 1 - 6 Hours Post-Idasanutlin/Placebo |
-3.4
(32.2)
|
19.0
(34.2)
|
| QT Duration Cycle 3 Day 2 |
-9.4
(13.6)
|
28.0
(35.3)
|
| QT Duration Study Drug Completion/Discontinuation |
-5.6
(36.2)
|
-4.8
(34.8)
|
| QTcB Baseline |
435.3
(30.9)
|
437.5
(31.1)
|
| QTcB Cycle 1 Day 1 Within 2 Hours Pre-Idasanutlin/Placebo |
8.7
(20.5)
|
4.8
(23.9)
|
| QTcB Cycle 1 Day 1 Post-Cytarabin |
1.3
(192)
|
3.8
(26.1)
|
| QTcB Cycle 1 Day 1 6 Hours Post-Idasanutlin/Placebo |
1.4
(24.8)
|
6.4
(39.5)
|
| QTcB Cycle 1 Day 2 |
-1.8
(22.8)
|
2.4
(25.9)
|
| QTcB Cycle 1 Day 5 Within 2 Hours Pre-Idasanutlin/Placeb |
-8.3
(26.2)
|
-3.2
(27.9)
|
| QTcB Cycle 1 Day 5 Post-Cytarabine |
-4.4
(28.7)
|
-3.7
(23.4)
|
| QTcB Cycle 1 Day 5 6 Hours Post-Idasanutlin/Placebo |
-5.2
(28.8)
|
-5.5
(24.0)
|
| QTcB Cycle 2 Day 1 - Within 2 Hours Pre-Idasanutlin/Placebo |
0.5
(15.7)
|
1.6
(32.0)
|
| QTcB Cycle 2 Day 1 Post-Cytarabine |
3.0
(24.8)
|
4.2
(45.0)
|
| QTcB Cycle 2 Day 1 6 Hours Post-Idasanutlin/Placebo |
6.5
(27.7)
|
4.6
(28.3)
|
| QTcB Cycle 2 Day 2 |
0.8
(28.6)
|
-1.0
(25.6)
|
| QTcB Cycle 3 Day 1 Within 2 Hours Pre-Idasanutlin/Placebo |
13.1
(24.3)
|
-1.1
(17.8)
|
| QTcB Cycle 3 Day 1 Post-Cytarabine |
16.6
(27.3)
|
13.6
(21.4)
|
| QTcB Cycle 3 Day 1 6 Hours Post-Idasanutlin/Placebo |
6.9
(24.6)
|
21.9
(28.6)
|
| QTcB Cycle 3 Day 2 |
1.4
(18.5)
|
14.3
(18.4)
|
| QTcB Study Drug Completion/Discontinuation |
1.9
(32.2)
|
5.8
(29.9)
|
| QTcF Baseline |
418.0
(28.5)
|
419.0
(26.6)
|
| QTcF Cycle 1 Day 1 Within 2 Hours Pre-Idasanutlin/Placebo |
7.6
(19.3)
|
5.1
(21.7)
|
| QTcF Cycle 1 Day 1 Post-Cytarabine |
1.0
(18.3)
|
4.1
(22.0)
|
| QTcF Cycle 1 Day 1 6 Hours Post-Idasanutlin/Placebo |
0.9
(23.4)
|
4.2
(28.6)
|
| QTcF Cycle 1 Day 2 |
1.3
(22.7)
|
2.6
(23.8)
|
| QTcF Cycle 1 Day 5 Within 2 Hours Pre-Idasanutlin/Placebo |
3.6
(23.7)
|
-1.1
(24.3)
|
| QTcF Cycle 1 Day 5 Post-Cytarabine |
6.1
(27.1)
|
-0.4
(22.6)
|
| QTcF Cycle 1 Day 5 6 Hours Post-Idasanutlin/Placebo |
6.0
(27.7)
|
-2.1
(22.2)
|
| QTcF Cycle 2 Day 1 Within 2 Hours Pre-Idasanutlin/Placebo |
0.0
(19.7)
|
4.0
(26.3)
|
| QTcF Cycle 2 Day 1 Post-Cytarabine |
0.5
(15.7)
|
6.4
(36.9)
|
| QTcF Cycle 2 Day 1 6 Hours Post-Idasanutlin/Placebo |
1.5
(21.1)
|
4.0
(26.8)
|
| QTcF Cycle 2 Day 2 |
6.1
(18.3)
|
1.1
(26.3)
|
| QTcF Cycle 3 Day 1 Within 2 Hours Pre-Idasanutlin/Placebo |
14.0
(21.6)
|
14.0
(21.6)
|
| QTcF Cycle 3 Day 1 - Post-Cytarabine |
18.5
(24.1)
|
16.8
(26.0)
|
| QTcF Cycle 3 Day 1 6 Hours Post-Idasanutlin/Placebo |
3.5
(25.2)
|
20.7
(24.7)
|
| QTcF Cycle 3 Day 2 |
-2.6
(14.5)
|
19.2
(25.6)
|
| QTcF Study Drug Completion/Discontinuation |
0.2
(28.3)
|
2.9
(26.5)
|
| RR Duration Baseline |
797.9
(139.6)
|
787.9
(151.7)
|
| RR Duration Cycle 1 Day 1 Within 2 Hours Pre-Idasanutlin/Placebo |
-2.5
(63.5)
|
4.8
(139.1)
|
| RR Duration Cycle 1 Day 1 Post-Cytarabine |
-4.7
(89.6)
|
3.6
(105.6)
|
| RR Duration Cycle 1 Day 1 6 Hours Post-Idasanutlin/Placebo |
-3.0
(103.4)
|
-19.1
(108.5)
|
| RR Duration Cycle 1 Day 2 |
37.6
(117.6)
|
4.1
(126.7)
|
| RR Duration Cycle 1 Day 5 Within 2 Hours Pre-Idasanutlin/Placebo |
159.3
(212.4)
|
19.5
(146.8)
|
| RR Duration Cycle 1 Day 5 Post-Cytarabine |
133.7
(164.9)
|
36.8
(151.5)
|
| RR Duration Cycle 1 Day 5 6 Hours Post-Idasanutlin/Placebo |
144.2
(167.6)
|
37.8
(150.5)
|
| RR Duration Cycle 2 Day 1 Within 2 Hours Pre-Idasanutlin/Placebo |
-5.4
(119.6)
|
25.7
(156.7)
|
| RR Duration Cycle 2 Day 1 Post-Cytarabine |
-38.8
(140.1)
|
23.3
(123.3)
|
| RR Duration Cycle 2 Day 1 6 Hours Post-Idasanutlin/Placebo |
-66.9
(176.4)
|
-15.2
(180.8)
|
| RR Duration Cycle 2 Day 2 |
57.9
(162.2)
|
14.1
(155.4)
|
| RR Duration Cycle 3 Day 1 Within 2 Hours Pre-Idasanutlin/Placebo |
15.1
(80.8)
|
65.5
(105.1)
|
| RR Duration Cycle 3 Day 1 Post-Cytarabine |
11.1
(132.8)
|
38.9
(75.0)
|
| RR Duration Cycle 3 Day 1 6 Hours Post-Idasanutlin/Placebo |
-49.4
(89.8)
|
3.3
(135.5)
|
| RR Duration Cycle 3 Day 2 |
-42.9
(72.0)
|
62.0
(120.3)
|
| RR Duration Study Drug Completion/Discontinuation |
-14.8
(170.6)
|
-14.8
(170.6)
|
| Title | Total Duration of Study Treatment |
|---|---|
| Description | Participants were planned to be treated up to 3 Cycles. |
| Time Frame | Up to 3 cycles (1 cycle is 28 days) |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT Population |
| Arm/Group Title | Idasanutlin Plus Cytarabine | Placebo Plus Cytarabine |
|---|---|---|
| Arm/Group Description | Participants received induction therapy idasanutlin and cytarabine for 5 days followed by 23 days of rest in Cycle 1 (treatment cycle length=28 days). Responding participants may continue with consolidation therapy for a maximum of 2 additional cycles including idasanutlin and cytarabine for 5 days followed by 23 days of rest in each cycle (treatment cycle length=28 days). After each cycle, for participants achieving CRp or complete remission with incomplete blood count recovery (CRi), up to 28 additional days are allowed for blood count recovery, if needed. | Participants received induction therapy idasanutlin matching placebo and cytarabine for 5 Days followed by 23 days of rest in Cycle 1 (treatment cycle length=28 days). Responding participants may continue with consolidation therapy for a maximum of 2 additional cycles including idasanutlin matching placebo and cytarabine for 5 days followed by 23 days of rest in each cycle (treatment cycle length=28 days). After each cycle, for participants achieving CRp or CRi, up to 28 additional days are allowed for blood count recovery, if needed. |
| Measure Participants | 149 | 292 |
| Mean (Standard Deviation) [Days] |
16.5
(28.29)
|
17.6
(28.25)
|
| Title | Number of Treatment Cycles Started |
|---|---|
| Description | Participants who started the study treatment cycles are reported. |
| Time Frame | Up to 3 cycles (1 cycle is 28 days) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Population |
| Arm/Group Title | Placebo Plus Cytarabine | Idasanutlin Plus Cytarabine |
|---|---|---|
| Arm/Group Description | Participants received induction therapy idasanutlin matching placebo and cytarabine for 5 Days followed by 23 days of rest in Cycle 1 (treatment cycle length=28 days). Responding participants may continue with consolidation therapy for a maximum of 2 additional cycles including idasanutlin matching placebo and cytarabine for 5 days followed by 23 days of rest in each cycle (treatment cycle length=28 days). After each cycle, for participants achieving CRp or CRi, up to 28 additional days are allowed for blood count recovery, if needed. | Participants received induction therapy idasanutlin and cytarabine for 5 days followed by 23 days of rest in Cycle 1 (treatment cycle length=28 days). Responding participants may continue with consolidation therapy for a maximum of 2 additional cycles including idasanutlin and cytarabine for 5 days followed by 23 days of rest in each cycle (treatment cycle length=28 days). After each cycle, for participants achieving CRp or complete remission with incomplete blood count recovery (CRi), up to 28 additional days are allowed for blood count recovery, if needed. |
| Measure Participants | 149 | 292 |
| Mean (Standard Deviation) [Treatment Cycles] |
1.3
(0.63)
|
1.2
(0.54)
|
| Title | Cumulative Dose of Idasanutlin and Cytarabine |
|---|---|
| Description | The cumulative doses of idasanutlin and cytaradine are reported. |
| Time Frame | Up to 3 cycles (1 cycle is 28 days) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Population. Participants did not receive Idasanutlin in the "Placebo Plus Cytarabine" Arm, so this data were not collected. |
| Arm/Group Title | Placebo Plus Cytarabine | Idasanutlin Plus Cytarabine |
|---|---|---|
| Arm/Group Description | Participants received induction therapy idasanutlin matching placebo and cytarabine for 5 Days followed by 23 days of rest in Cycle 1 (treatment cycle length=28 days). Responding participants may continue with consolidation therapy for a maximum of 2 additional cycles including idasanutlin matching placebo and cytarabine for 5 days followed by 23 days of rest in each cycle (treatment cycle length=28 days). After each cycle, for participants achieving CRp or CRi, up to 28 additional days are allowed for blood count recovery, if needed. | Participants received induction therapy idasanutlin and cytarabine for 5 days followed by 23 days of rest in Cycle 1 (treatment cycle length=28 days). Responding participants may continue with consolidation therapy for a maximum of 2 additional cycles including idasanutlin and cytarabine for 5 days followed by 23 days of rest in each cycle (treatment cycle length=28 days). After each cycle, for participants achieving CRp or complete remission with incomplete blood count recovery (CRi), up to 28 additional days are allowed for blood count recovery, if needed. |
| Measure Participants | 149 | 292 |
| Idasanutlin/Placebo cumulative dose (mg) |
3340.1
(896.35)
|
|
| Cytarabine cumulative dose (mg) |
11500
(5850)
|
11200
(5190)
|
| Title | Apparent Clearance (CL/F) of Idasanutlin |
|---|---|
| Description | Apparent Clearance (CL/F) of Idasanutlin was planned as part of the PK analyses. The Independent Data Monitoring Committee recommended stopping the study for futility based on a lack of OS benefit due to Hazard Ratio (HR) being greater than 1. The benefit-risk profile of idasanutlin combined with 1g/m2 cytarabine in fit R/R AML was not positive, as the observed marginal benefit does not outweigh the risks of idasanutlin in the relapsed or refractory AML population. Therefore the study was prematurely terminated by the sponsor's decision and the result data did not derive.The benefit-risk profile of idasanutlin combined with 1g/m2 cytarabine in fit R/R AML was not positive, as the observed marginal benefit does not outweigh the risks of idasanutlin in the relapsed or refractory AML population. The planned CL/F did not derive for the result data and was not reported. |
| Time Frame | Cycle 1: Predose (0 hour [Hr]), end of 1-3 Hr cytarabine infusion, 6 Hr postdose on Days 1, 5; Predose (0 Hr) on Day 2; at Days 8, 10; Cycle 2, 3: predose (0 Hr) on Days 2, 5 (predose/postdose: relative to idasanutlin morning dose; cycle length= 28 days) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Due to futility the planned participant enrollment was observed, therefore result data were not collected. |
| Arm/Group Title | Placebo Plus Cytarabine | Idasanutlin Plus Cytarabine |
|---|---|---|
| Arm/Group Description | Participants received induction therapy idasanutlin matching placebo and cytarabine for 5 Days followed by 23 days of rest in Cycle 1 (treatment cycle length=28 days). Responding participants may continue with consolidation therapy for a maximum of 2 additional cycles including idasanutlin matching placebo and cytarabine for 5 days followed by 23 days of rest in each cycle (treatment cycle length=28 days). After each cycle, for participants achieving CRp or CRi, up to 28 additional days are allowed for blood count recovery, if needed. | Participants received induction therapy idasanutlin and cytarabine for 5 days followed by 23 days of rest in Cycle 1 (treatment cycle length=28 days). Responding participants may continue with consolidation therapy for a maximum of 2 additional cycles including idasanutlin and cytarabine for 5 days followed by 23 days of rest in each cycle (treatment cycle length=28 days). After each cycle, for participants achieving CRp or complete remission with incomplete blood count recovery (CRi), up to 28 additional days are allowed for blood count recovery, if needed. |
| Measure Participants | 0 | 0 |
| Title | Apparent Volume of Distribution (Vd/F) of Idasanutlin |
|---|---|
| Description | Apparent Volume of Distribution (Vd/F) of Idasanutlin was planned as part of the PK analyses. The Independent Data Monitoring Committee recommended stopping the study for futility based on a lack of OS benefit due to Hazard Ratio (HR) being greater than 1. The benefit-risk profile of idasanutlin combined with 1g/m2 cytarabine in fit R/R AML was not positive, as the observed marginal benefit does not outweigh the risks of idasanutlin in the relapsed or refractory AML population. Therefore the study was prematurely terminated by the sponsor's decision and the result data did not derive. |
| Time Frame | Cycle 1: Predose (0 Hr), end of 1-3 Hr cytarabine infusion, 6 Hr postdose on Days 1, 5; Predose (0 Hr) on Day 2; at Days 8, 10; Cycle 2, 3: predose (0 Hr) on Days 2, 5 (predose/postdose: relative to idasanutlin morning dose; cycle length= 28 days) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Due to insufficient participant compliance the planned enrollment was observed, therefore result data were not collected. |
| Arm/Group Title | Placebo Plus Cytarabine | Idasanutlin Plus Cytarabine |
|---|---|---|
| Arm/Group Description | Participants received induction therapy idasanutlin matching placebo and cytarabine for 5 Days followed by 23 days of rest in Cycle 1 (treatment cycle length=28 days). Responding participants may continue with consolidation therapy for a maximum of 2 additional cycles including idasanutlin matching placebo and cytarabine for 5 days followed by 23 days of rest in each cycle (treatment cycle length=28 days). After each cycle, for participants achieving CRp or CRi, up to 28 additional days are allowed for blood count recovery, if needed. | Participants received induction therapy idasanutlin and cytarabine for 5 days followed by 23 days of rest in Cycle 1 (treatment cycle length=28 days). Responding participants may continue with consolidation therapy for a maximum of 2 additional cycles including idasanutlin and cytarabine for 5 days followed by 23 days of rest in each cycle (treatment cycle length=28 days). After each cycle, for participants achieving CRp or complete remission with incomplete blood count recovery (CRi), up to 28 additional days are allowed for blood count recovery, if needed. |
| Measure Participants | 0 | 0 |
| Title | Maximum Concentration Observed (Cmax) of Idasanutlin |
|---|---|
| Description | Maximum Concentration Observed (Cmax) of Idasanutlin was planned as part of the PK analyses. The Independent Data Monitoring Committee recommended stopping the study for futility based on a lack of OS benefit due to Hazard Ratio (HR) being greater than 1. The benefit-risk profile of idasanutlin combined with 1g/m2 cytarabine in fit R/R AML was not positive, as the observed marginal benefit does not outweigh the risks of idasanutlin in the relapsed or refractory AML population. Therefore the study was prematurely terminated by the sponsor's decision and the result data did not derive. |
| Time Frame | Cycle 1: Predose (0 Hr), end of 1-3 Hr cytarabine infusion, 6 Hr postdose on Days 1, 5; Predose (0 Hr) on Day 2; at Days 8, 10; Cycle 2, 3: predose (0 Hr) on Days 2, 5 (predose/postdose: relative to idasanutlin morning dose; cycle length= 28 days) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Due to insufficient participant compliance the planned enrollment was observed, therefore result data were not collected. |
| Arm/Group Title | Placebo Plus Cytarabine | Idasanutlin Plus Cytarabine |
|---|---|---|
| Arm/Group Description | Participants received induction therapy idasanutlin matching placebo and cytarabine for 5 Days followed by 23 days of rest in Cycle 1 (treatment cycle length=28 days). Responding participants may continue with consolidation therapy for a maximum of 2 additional cycles including idasanutlin matching placebo and cytarabine for 5 days followed by 23 days of rest in each cycle (treatment cycle length=28 days). After each cycle, for participants achieving CRp or CRi, up to 28 additional days are allowed for blood count recovery, if needed. | Participants received induction therapy idasanutlin and cytarabine for 5 days followed by 23 days of rest in Cycle 1 (treatment cycle length=28 days). Responding participants may continue with consolidation therapy for a maximum of 2 additional cycles including idasanutlin and cytarabine for 5 days followed by 23 days of rest in each cycle (treatment cycle length=28 days). After each cycle, for participants achieving CRp or complete remission with incomplete blood count recovery (CRi), up to 28 additional days are allowed for blood count recovery, if needed. |
| Measure Participants | 0 | 0 |
| Title | Steady-State Concentration (Ctrough) of Idasanutlin |
|---|---|
| Description | Steady-State Concentration (Ctrough) of Idasanutlin was planned as part of the PK analyses. The Independent Data Monitoring Committee recommended stopping the study for futility based on a lack of OS benefit due to Hazard Ratio (HR) being greater than 1. The benefit-risk profile of idasanutlin combined with 1g/m2 cytarabine in fit R/R AML was not positive, as the observed marginal benefit does not outweigh the risks of idasanutlin in the relapsed or refractory AML population. Therefore the study was prematurely terminated by the sponsor's decision and the result data did not derive. |
| Time Frame | Cycle 1: Predose (0 Hr), end of 1-3 Hr cytarabine infusion, 6 Hr postdose on Days 1, 5; Predose (0 Hr) on Day 2; at Days 8, 10; Cycle 2, 3: predose (0 Hr) on Days 2, 5 (predose/postdose: relative to idasanutlin morning dose; cycle length= 28 days) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Due to insufficient participant compliance the planned enrollment was observed, therefore result data were not collected. |
| Arm/Group Title | Placebo Plus Cytarabine | Idasanutlin Plus Cytarabine |
|---|---|---|
| Arm/Group Description | Participants received induction therapy idasanutlin matching placebo and cytarabine for 5 Days followed by 23 days of rest in Cycle 1 (treatment cycle length=28 days). Responding participants may continue with consolidation therapy for a maximum of 2 additional cycles including idasanutlin matching placebo and cytarabine for 5 days followed by 23 days of rest in each cycle (treatment cycle length=28 days). After each cycle, for participants achieving CRp or CRi, up to 28 additional days are allowed for blood count recovery, if needed. | Participants received induction therapy idasanutlin and cytarabine for 5 days followed by 23 days of rest in Cycle 1 (treatment cycle length=28 days). Responding participants may continue with consolidation therapy for a maximum of 2 additional cycles including idasanutlin and cytarabine for 5 days followed by 23 days of rest in each cycle (treatment cycle length=28 days). After each cycle, for participants achieving CRp or complete remission with incomplete blood count recovery (CRi), up to 28 additional days are allowed for blood count recovery, if needed. |
| Measure Participants | 0 | 0 |
| Title | Area Under the Concentration-Time Curve (AUC) During One Dosing Interval (AUCtau) of Idasanutlin |
|---|---|
| Description | Area Under the Concentration-Time Curve (AUC) During One Dosing Interval (AUCtau) of Idasanutlin was planned as part of the PK analyses. The Independent Data Monitoring Committee recommended stopping the study for futility based on a lack of OS benefit due to Hazard Ratio (HR) being greater than 1. The benefit-risk profile of idasanutlin combined with 1g/m2 cytarabine in fit R/R AML was not positive, as the observed marginal benefit does not outweigh the risks of idasanutlin in the relapsed or refractory AML population. Therefore the study was prematurely terminated by the sponsor's decision and the result data did not derive. |
| Time Frame | Cycle 1: Predose (0 Hr), end of 1-3 Hr cytarabine infusion, 6 Hr postdose on Days 1, 5; Predose (0 Hr) on Day 2; at Days 8, 10; Cycle 2, 3: predose (0 Hr) on Days 2, 5 (predose/postdose: relative to idasanutlin morning dose; cycle length= 28 days) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Due to insufficient participant compliance the planned enrollment was observed, therefore result data were not collected. |
| Arm/Group Title | Placebo Plus Cytarabine | Idasanutlin Plus Cytarabine |
|---|---|---|
| Arm/Group Description | Participants received induction therapy idasanutlin matching placebo and cytarabine for 5 Days followed by 23 days of rest in Cycle 1 (treatment cycle length=28 days). Responding participants may continue with consolidation therapy for a maximum of 2 additional cycles including idasanutlin matching placebo and cytarabine for 5 days followed by 23 days of rest in each cycle (treatment cycle length=28 days). After each cycle, for participants achieving CRp or CRi, up to 28 additional days are allowed for blood count recovery, if needed. | Participants received induction therapy idasanutlin and cytarabine for 5 days followed by 23 days of rest in Cycle 1 (treatment cycle length=28 days). Responding participants may continue with consolidation therapy for a maximum of 2 additional cycles including idasanutlin and cytarabine for 5 days followed by 23 days of rest in each cycle (treatment cycle length=28 days). After each cycle, for participants achieving CRp or complete remission with incomplete blood count recovery (CRi), up to 28 additional days are allowed for blood count recovery, if needed. |
| Measure Participants | 0 | 0 |
| Title | AUC From Time Zero to 24 Hours Post Dose (AUC0-24) of Idasanutlin |
|---|---|
| Description | AUC from Time Zero to 24 Hours Post Dose (AUC0-24) of Idasanutlin was planned as part of the PK analyses. The Independent Data Monitoring Committee recommended stopping the study for futility based on a lack of OS benefit due to Hazard Ratio (HR) being greater than 1. The benefit-risk profile of idasanutlin combined with 1g/m2 cytarabine in fit R/R AML was not positive, as the observed marginal benefit does not outweigh the risks of idasanutlin in the relapsed or refractory AML population. Therefore the study was prematurely terminated by the sponsor's decision and the result data did not derive. |
| Time Frame | Cycle 1: Predose (0 Hr), end of 1-3 Hr cytarabine infusion, 6 Hr postdose on Days 1, 5; Predose (0 Hr) on Day 2; at Days 8, 10; Cycle 2, 3: predose (0 Hr) on Days 2, 5 (predose/postdose: relative to idasanutlin morning dose; cycle length= 28 days) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Due to insufficient participant compliance the planned enrollment was observed, therefore result data were not collected. |
| Arm/Group Title | Placebo Plus Cytarabine | Idasanutlin Plus Cytarabine |
|---|---|---|
| Arm/Group Description | Participants received induction therapy idasanutlin matching placebo and cytarabine for 5 Days followed by 23 days of rest in Cycle 1 (treatment cycle length=28 days). Responding participants may continue with consolidation therapy for a maximum of 2 additional cycles including idasanutlin matching placebo and cytarabine for 5 days followed by 23 days of rest in each cycle (treatment cycle length=28 days). After each cycle, for participants achieving CRp or CRi, up to 28 additional days are allowed for blood count recovery, if needed. | Participants received induction therapy idasanutlin and cytarabine for 5 days followed by 23 days of rest in Cycle 1 (treatment cycle length=28 days). Responding participants may continue with consolidation therapy for a maximum of 2 additional cycles including idasanutlin and cytarabine for 5 days followed by 23 days of rest in each cycle (treatment cycle length=28 days). After each cycle, for participants achieving CRp or complete remission with incomplete blood count recovery (CRi), up to 28 additional days are allowed for blood count recovery, if needed. |
| Measure Participants | 0 | 0 |
| Title | Half-Life (t 1/2) of Idasanutlin |
|---|---|
| Description | Half-Life (t 1/2) of Idasanutlin was planned as part of the PK analyses. The Independent Data Monitoring Committee recommended stopping the study for futility based on a lack of OS benefit due to Hazard Ratio (HR) being greater than 1. The benefit-risk profile of idasanutlin combined with 1g/m2 cytarabine in fit R/R AML was not positive, as the observed marginal benefit does not outweigh the risks of idasanutlin in the relapsed or refractory AML population. Therefore the study was prematurely terminated by the sponsor's decision and the result data did not derive. |
| Time Frame | Cycle 1: Predose (0 Hr), end of 1-3 Hr cytarabine infusion, 6 Hr postdose on Days 1, 5; Predose (0 Hr) on Day 2; at Days 8, 10; Cycle 2, 3: predose (0 Hr) on Days 2, 5 (predose/postdose: relative to idasanutlin morning dose; cycle length= 28 days) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Due to insufficient participant compliance the planned enrollment was observed, therefore result data were not collected. |
| Arm/Group Title | Placebo Plus Cytarabine | Idasanutlin Plus Cytarabine |
|---|---|---|
| Arm/Group Description | Participants received induction therapy idasanutlin matching placebo and cytarabine for 5 Days followed by 23 days of rest in Cycle 1 (treatment cycle length=28 days). Responding participants may continue with consolidation therapy for a maximum of 2 additional cycles including idasanutlin matching placebo and cytarabine for 5 days followed by 23 days of rest in each cycle (treatment cycle length=28 days). After each cycle, for participants achieving CRp or CRi, up to 28 additional days are allowed for blood count recovery, if needed. | Participants received induction therapy idasanutlin and cytarabine for 5 days followed by 23 days of rest in Cycle 1 (treatment cycle length=28 days). Responding participants may continue with consolidation therapy for a maximum of 2 additional cycles including idasanutlin and cytarabine for 5 days followed by 23 days of rest in each cycle (treatment cycle length=28 days). After each cycle, for participants achieving CRp or complete remission with incomplete blood count recovery (CRi), up to 28 additional days are allowed for blood count recovery, if needed. |
| Measure Participants | 0 | 0 |
| Title | Total Clearance (CL) of Cytarabine |
|---|---|
| Description | The Total Clearance (CL) of Cytarabine was planned as part of the PK analyses. The Independent Data Monitoring Committee recommended stopping the study for futility based on a lack of OS benefit due to Hazard Ratio (HR) being greater than 1. The benefit-risk profile of idasanutlin combined with 1g/m2 cytarabine in fit R/R AML was not positive, as the observed marginal benefit does not outweigh the risks of idasanutlin in the relapsed or refractory AML population. Therefore the study was prematurely terminated by the sponsor's decision and the result data did not derive. |
| Time Frame | Cycle 1: Within 2 Hr pre-cytarabine dose, end of 1-3 Hr cytarabine infusion, 6 Hr post idasanutlin morning dose on Days 1, 5; Within 2 Hr pre-cytarabine dose on Day 2; Cycle 2, 3: Within 2 Hr pre-cytarabine dose on Day 2 (Cycle length= 28 days) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Due to insufficient participant compliance the planned enrollment was observed, therefore result data were not collected. |
| Arm/Group Title | Placebo Plus Cytarabine | Idasanutlin Plus Cytarabine |
|---|---|---|
| Arm/Group Description | Participants received induction therapy idasanutlin matching placebo and cytarabine for 5 Days followed by 23 days of rest in Cycle 1 (treatment cycle length=28 days). Responding participants may continue with consolidation therapy for a maximum of 2 additional cycles including idasanutlin matching placebo and cytarabine for 5 days followed by 23 days of rest in each cycle (treatment cycle length=28 days). After each cycle, for participants achieving CRp or CRi, up to 28 additional days are allowed for blood count recovery, if needed. | Participants received induction therapy idasanutlin and cytarabine for 5 days followed by 23 days of rest in Cycle 1 (treatment cycle length=28 days). Responding participants may continue with consolidation therapy for a maximum of 2 additional cycles including idasanutlin and cytarabine for 5 days followed by 23 days of rest in each cycle (treatment cycle length=28 days). After each cycle, for participants achieving CRp or complete remission with incomplete blood count recovery (CRi), up to 28 additional days are allowed for blood count recovery, if needed. |
| Measure Participants | 0 | 0 |
| Title | Volume of Distribution (Vd) of Cytarabine |
|---|---|
| Description | The Volume of Distribution (Vd) of Cytarabine was planned as part of the PK analyses. The Independent Data Monitoring Committee recommended stopping the study for futility based on a lack of OS benefit due to Hazard Ratio (HR) being greater than 1. The benefit-risk profile of idasanutlin combined with 1g/m2 cytarabine in fit R/R AML was not positive, as the observed marginal benefit does not outweigh the risks of idasanutlin in the relapsed or refractory AML population. Therefore the study was prematurely terminated by the sponsor's decision and the result data did not derive. |
| Time Frame | Cycle 1: Within 2 Hr pre-cytarabine dose, end of 1-3 Hr cytarabine infusion, 6 Hr post idasanutlin morning dose on Days 1, 5; Within 2 Hr pre-cytarabine dose on Day 2; Cycle 2, 3: Within 2 Hr pre-cytarabine dose on Day 2 (Cycle length= 28 days) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Due to insufficient participant compliance the planned enrollment was observed, therefore result data were not collected. |
| Arm/Group Title | Placebo Plus Cytarabine | Idasanutlin Plus Cytarabine |
|---|---|---|
| Arm/Group Description | Participants received induction therapy idasanutlin matching placebo and cytarabine for 5 Days followed by 23 days of rest in Cycle 1 (treatment cycle length=28 days). Responding participants may continue with consolidation therapy for a maximum of 2 additional cycles including idasanutlin matching placebo and cytarabine for 5 days followed by 23 days of rest in each cycle (treatment cycle length=28 days). After each cycle, for participants achieving CRp or CRi, up to 28 additional days are allowed for blood count recovery, if needed. | Participants received induction therapy idasanutlin and cytarabine for 5 days followed by 23 days of rest in Cycle 1 (treatment cycle length=28 days). Responding participants may continue with consolidation therapy for a maximum of 2 additional cycles including idasanutlin and cytarabine for 5 days followed by 23 days of rest in each cycle (treatment cycle length=28 days). After each cycle, for participants achieving CRp or complete remission with incomplete blood count recovery (CRi), up to 28 additional days are allowed for blood count recovery, if needed. |
| Measure Participants | 0 | 0 |
| Title | Change From Baseline in European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Score |
|---|---|
| Description | The compliance rate (defined as the number of patients who completed as least 1 question on the measure) at baseline was 56% and 61% for the Idasanutlin arm and the placebo arm, respectively. This compliance rate remained the same post-baseline in both arms. Due to the low compliance rates in both arms during the entire treatment period, the planned analyses were not performed. |
| Time Frame | Cycle 1 Day 1 (Baseline), Days 8, 15, 28 of Cycle 1, Days 1, 8, 15, 28 of Cycles 2, 3, 28 days after last dose (last dose on Cycle 3 Day 5), thereafter every 3 months until relapse (maximum up to 3.5 years) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Due to insufficient participant compliance rate, an insufficient enrollment was observed and result data were not collected. |
| Arm/Group Title | Placebo Plus Cytarabine | Idasanutlin Plus Cytarabine |
|---|---|---|
| Arm/Group Description | Participants received induction therapy idasanutlin matching placebo and cytarabine for 5 Days followed by 23 days of rest in Cycle 1 (treatment cycle length=28 days). Responding participants may continue with consolidation therapy for a maximum of 2 additional cycles including idasanutlin matching placebo and cytarabine for 5 days followed by 23 days of rest in each cycle (treatment cycle length=28 days). After each cycle, for participants achieving CRp or CRi, up to 28 additional days are allowed for blood count recovery, if needed. | Participants received induction therapy idasanutlin and cytarabine for 5 days followed by 23 days of rest in Cycle 1 (treatment cycle length=28 days). Responding participants may continue with consolidation therapy for a maximum of 2 additional cycles including idasanutlin and cytarabine for 5 days followed by 23 days of rest in each cycle (treatment cycle length=28 days). After each cycle, for participants achieving CRp or complete remission with incomplete blood count recovery (CRi), up to 28 additional days are allowed for blood count recovery, if needed. |
| Measure Participants | 0 | 0 |
| Title | Change From Baseline in EuroQol 5 Dimension 5-Level (EQ-5D-5L) Questionnaire Score |
|---|---|
| Description | The compliance rate (defined as the number of patients who completed as least 1 question on the measure) at baseline was 56% and 61% for the Idasanutlin arm and the placebo arm, respectively. Compliance remained the same post-baseline in both arms Due to the low compliance rates in both arms during the entire treatment period, the planned analyses were not performed. |
| Time Frame | Cycle 1 Day 1 (Baseline), Days 8, 15, 28 of Cycle 1, Days 1, 8, 15, 28 of Cycles 2, 3, 28 days after last dose (last dose on Cycle 3 Day 5), thereafter every 3 months until relapse (maximum up to 3.5 years) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Due to insufficient participant compliance the planned enrollment was observed, therefore result data were not collected. |
| Arm/Group Title | Placebo Plus Cytarabine | Idasanutlin Plus Cytarabine |
|---|---|---|
| Arm/Group Description | Participants received induction therapy idasanutlin matching placebo and cytarabine for 5 Days followed by 23 days of rest in Cycle 1 (treatment cycle length=28 days). Responding participants may continue with consolidation therapy for a maximum of 2 additional cycles including idasanutlin matching placebo and cytarabine for 5 days followed by 23 days of rest in each cycle (treatment cycle length=28 days). After each cycle, for participants achieving CRp or CRi, up to 28 additional days are allowed for blood count recovery, if needed. | Participants received induction therapy idasanutlin and cytarabine for 5 days followed by 23 days of rest in Cycle 1 (treatment cycle length=28 days). Responding participants may continue with consolidation therapy for a maximum of 2 additional cycles including idasanutlin and cytarabine for 5 days followed by 23 days of rest in each cycle (treatment cycle length=28 days). After each cycle, for participants achieving CRp or complete remission with incomplete blood count recovery (CRi), up to 28 additional days are allowed for blood count recovery, if needed. |
| Measure Participants | 0 | 0 |
Adverse Events
| Time Frame | The timeframe was planned to be from the Baseline up to approximately 4.5 years. The study was pre-maturely terminated due to mild benefit by the sponsor's decision, therefore did not reach the planned end of study. | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | Reported: Safety Evaluable Population. During the Safety Follow-up Period, non-Serious Adverse Events occurred at the 5% frequency threshold. In Idasanutlin-Cytarabine Arm, total of 298 participants were enrolled of but 5 participants were not treated, 1 participant did not receive Idasanutlin and was moved to the Placebo Arm. In Placebo Arm, total 149 participants were enrolled,1 participant was not treated and 1 participant entered from the Idasanutlin Arm. | |||
| Arm/Group Title | Idasanutlin-Cytarabine | Placebo-Cytarabine | ||
| Arm/Group Description | Participants will receive induction therapy idasanutlin and cytarabine for 5 days followed by 23 days of rest in Cycle 1 (treatment cycle length=28 days). Responding participants may continue with consolidation therapy for a maximum of 2 additional cycles including idasanutlin and cytarabine for 5 days followed by 23 days of rest in each cycle (treatment cycle length=28 days). After each cycle, for participants achieving CRp or complete remission with incomplete blood count recovery (CRi), up to 28 additional days are allowed for blood count recovery, if needed | Participants will receive induction therapy idasanutlin matching placebo and cytarabine for 5 days followed by 23 days of rest in Cycle 1 (treatment cycle length=28 days). Responding participants may continue with consolidation therapy for a maximum of 2 additional cycles including idasanutlin matching placebo and cytarabine for 5 days followed by 23 days of rest in each cycle (treatment cycle length=28 days). After each cycle, for participants achieving CRp or CRi, up to 28 additional days are allowed for blood count recovery, if needed. | ||
All Cause Mortality |
||||
| Idasanutlin-Cytarabine | Placebo-Cytarabine | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 211/292 (72.3%) | 109/149 (73.2%) | ||
Serious Adverse Events |
||||
| Idasanutlin-Cytarabine | Placebo-Cytarabine | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 173/292 (59.2%) | 72/149 (48.3%) | ||
| Blood and lymphatic system disorders | ||||
| Cytopenia | 1/292 (0.3%) | 1 | 0/149 (0%) | 0 |
| Febrile bone marrow aplasia | 1/292 (0.3%) | 1 | 0/149 (0%) | 0 |
| Febrile neutropenia | 28/292 (9.6%) | 37 | 13/149 (8.7%) | 16 |
| Leukopenia | 1/292 (0.3%) | 1 | 0/149 (0%) | 0 |
| Neutropenia | 3/292 (1%) | 3 | 0/149 (0%) | 0 |
| Pancytopenia | 2/292 (0.7%) | 2 | 0/149 (0%) | 0 |
| Thrombocytopenia | 4/292 (1.4%) | 4 | 2/149 (1.3%) | 2 |
| Cardiac disorders | ||||
| Acute coronary syndrome | 1/292 (0.3%) | 1 | 0/149 (0%) | 0 |
| Atrial fibrillation | 1/292 (0.3%) | 1 | 0/149 (0%) | 0 |
| Bundle branch block right | 0/292 (0%) | 0 | 1/149 (0.7%) | 1 |
| Cardiac arrest | 1/292 (0.3%) | 1 | 0/149 (0%) | 0 |
| Cardiac tamponade | 1/292 (0.3%) | 1 | 0/149 (0%) | 0 |
| Myocardial infarction | 1/292 (0.3%) | 1 | 1/149 (0.7%) | 1 |
| Myocarditis | 0/292 (0%) | 0 | 2/149 (1.3%) | 2 |
| Pericardial effusion | 1/292 (0.3%) | 1 | 0/149 (0%) | 0 |
| Pericarditis | 2/292 (0.7%) | 2 | 0/149 (0%) | 0 |
| Sinus bradycardia | 1/292 (0.3%) | 1 | 0/149 (0%) | 0 |
| Sinus tachycardia | 1/292 (0.3%) | 1 | 0/149 (0%) | 0 |
| Gastrointestinal disorders | ||||
| Colitis | 1/292 (0.3%) | 1 | 0/149 (0%) | 0 |
| Colitis ischaemic | 1/292 (0.3%) | 1 | 0/149 (0%) | 0 |
| Diarrhoea | 8/292 (2.7%) | 8 | 1/149 (0.7%) | 1 |
| Gastric haemorrhage | 1/292 (0.3%) | 1 | 0/149 (0%) | 0 |
| Ileus paralytic | 1/292 (0.3%) | 1 | 0/149 (0%) | 0 |
| Intestinal haemorrhage | 1/292 (0.3%) | 1 | 1/149 (0.7%) | 1 |
| Large intestinal obstruction | 1/292 (0.3%) | 1 | 0/149 (0%) | 0 |
| Melaena | 1/292 (0.3%) | 1 | 0/149 (0%) | 0 |
| Pancreatitis | 2/292 (0.7%) | 2 | 0/149 (0%) | 0 |
| Small intestinal obstruction | 1/292 (0.3%) | 1 | 0/149 (0%) | 0 |
| Tongue haematoma | 1/292 (0.3%) | 1 | 0/149 (0%) | 0 |
| Vomiting | 1/292 (0.3%) | 1 | 0/149 (0%) | 0 |
| General disorders | ||||
| Death | 6/292 (2.1%) | 6 | 1/149 (0.7%) | 1 |
| General physical health deterioration | 1/292 (0.3%) | 1 | 0/149 (0%) | 0 |
| Injection site extravasation | 0/292 (0%) | 0 | 1/149 (0.7%) | 1 |
| Multiple organ dysfunction syndrome | 6/292 (2.1%) | 6 | 2/149 (1.3%) | 2 |
| Pyrexia | 6/292 (2.1%) | 7 | 1/149 (0.7%) | 1 |
| Hepatobiliary disorders | ||||
| Cholecystitis | 1/292 (0.3%) | 1 | 0/149 (0%) | 0 |
| Cholecystitis acute | 0/292 (0%) | 0 | 1/149 (0.7%) | 1 |
| Hepatic failure | 1/292 (0.3%) | 1 | 1/149 (0.7%) | 1 |
| Hepatitis acute | 0/292 (0%) | 0 | 1/149 (0.7%) | 1 |
| Hepatocellular injury | 1/292 (0.3%) | 1 | 0/149 (0%) | 0 |
| Hepatotoxicity | 1/292 (0.3%) | 1 | 0/149 (0%) | 0 |
| Hyperbilirubinaemia | 6/292 (2.1%) | 6 | 1/149 (0.7%) | 1 |
| Ocular icterus | 1/292 (0.3%) | 1 | 0/149 (0%) | 0 |
| Venoocclusive liver disease | 1/292 (0.3%) | 1 | 0/149 (0%) | 0 |
| Immune system disorders | ||||
| Acute graft versus host disease | 1/292 (0.3%) | 1 | 0/149 (0%) | 0 |
| Acute graft versus host disease in intestine | 0/292 (0%) | 0 | 1/149 (0.7%) | 1 |
| Anaphylactic shock | 1/292 (0.3%) | 1 | 0/149 (0%) | 0 |
| Chronic graft versus host disease | 1/292 (0.3%) | 1 | 1/149 (0.7%) | 1 |
| Graft versus host disease | 4/292 (1.4%) | 4 | 1/149 (0.7%) | 1 |
| Graft versus host disease in gastrointestinal tract | 3/292 (1%) | 3 | 1/149 (0.7%) | 1 |
| Haemophagocytic lymphohistiocytosis | 1/292 (0.3%) | 1 | 0/149 (0%) | 0 |
| Infections and infestations | ||||
| Anal abscess | 1/292 (0.3%) | 1 | 0/149 (0%) | 0 |
| Anal infection | 2/292 (0.7%) | 3 | 0/149 (0%) | 0 |
| Appendicitis | 0/292 (0%) | 0 | 1/149 (0.7%) | 1 |
| Aspergillus infection | 1/292 (0.3%) | 1 | 0/149 (0%) | 0 |
| Bacteraemia | 4/292 (1.4%) | 5 | 1/149 (0.7%) | 1 |
| Bacterial infection | 1/292 (0.3%) | 1 | 1/149 (0.7%) | 1 |
| Bacterial sepsis | 2/292 (0.7%) | 2 | 1/149 (0.7%) | 1 |
| Bronchopulmonary aspergillosis | 1/292 (0.3%) | 1 | 0/149 (0%) | 0 |
| Clostridium difficile infection | 2/292 (0.7%) | 2 | 0/149 (0%) | 0 |
| Device related infection | 2/292 (0.7%) | 2 | 1/149 (0.7%) | 1 |
| Device related sepsis | 1/292 (0.3%) | 1 | 0/149 (0%) | 0 |
| Diverticulitis | 1/292 (0.3%) | 1 | 0/149 (0%) | 0 |
| Encephalitis | 1/292 (0.3%) | 1 | 0/149 (0%) | 0 |
| Endocarditis | 2/292 (0.7%) | 2 | 0/149 (0%) | 0 |
| Enterobacter sepsis | 1/292 (0.3%) | 1 | 0/149 (0%) | 0 |
| Enterococcal sepsis | 0/292 (0%) | 0 | 1/149 (0.7%) | 1 |
| Enterocolitis infectious | 1/292 (0.3%) | 1 | 0/149 (0%) | 0 |
| Escherichia bacteraemia | 1/292 (0.3%) | 1 | 0/149 (0%) | 0 |
| Escherichia sepsis | 1/292 (0.3%) | 1 | 1/149 (0.7%) | 1 |
| Fusobacterium infection | 0/292 (0%) | 0 | 1/149 (0.7%) | 1 |
| Gingivitis | 1/292 (0.3%) | 1 | 0/149 (0%) | 0 |
| Herpes simplex | 1/292 (0.3%) | 1 | 0/149 (0%) | 0 |
| Infection | 1/292 (0.3%) | 1 | 0/149 (0%) | 0 |
| Klebsiella infection | 0/292 (0%) | 0 | 1/149 (0.7%) | 1 |
| Klebsiella sepsis | 1/292 (0.3%) | 1 | 0/149 (0%) | 0 |
| Lower respiratory tract infection | 1/292 (0.3%) | 1 | 0/149 (0%) | 0 |
| Neutropenic infection | 1/292 (0.3%) | 2 | 0/149 (0%) | 0 |
| Neutropenic sepsis | 5/292 (1.7%) | 6 | 2/149 (1.3%) | 2 |
| Periorbital cellulitis | 2/292 (0.7%) | 2 | 0/149 (0%) | 0 |
| Pneumonia | 21/292 (7.2%) | 21 | 13/149 (8.7%) | 13 |
| Pseudomonas infection | 1/292 (0.3%) | 1 | 0/149 (0%) | 0 |
| Pulmonary sepsis | 2/292 (0.7%) | 2 | 0/149 (0%) | 0 |
| Respiratory syncytial virus infection | 1/292 (0.3%) | 1 | 0/149 (0%) | 0 |
| Respiratory tract infection | 1/292 (0.3%) | 1 | 0/149 (0%) | 0 |
| Sepsis | 34/292 (11.6%) | 34 | 8/149 (5.4%) | 8 |
| Septic shock | 11/292 (3.8%) | 11 | 8/149 (5.4%) | 8 |
| Soft tissue infection | 1/292 (0.3%) | 1 | 0/149 (0%) | 0 |
| Staphylococcal sepsis | 2/292 (0.7%) | 2 | 0/149 (0%) | 0 |
| Streptococcal bacteraemia | 2/292 (0.7%) | 2 | 0/149 (0%) | 0 |
| Systemic candida | 1/292 (0.3%) | 1 | 0/149 (0%) | 0 |
| Upper respiratory tract infection | 2/292 (0.7%) | 2 | 1/149 (0.7%) | 1 |
| Vascular device infection | 0/292 (0%) | 0 | 1/149 (0.7%) | 1 |
| Viral infection | 1/292 (0.3%) | 1 | 0/149 (0%) | 0 |
| Vulvovaginitis | 1/292 (0.3%) | 1 | 0/149 (0%) | 0 |
| Injury, poisoning and procedural complications | ||||
| Anaphylactic transfusion reaction | 1/292 (0.3%) | 1 | 0/149 (0%) | 0 |
| Lower limb fracture | 0/292 (0%) | 0 | 1/149 (0.7%) | 1 |
| Subdural haematoma | 1/292 (0.3%) | 1 | 0/149 (0%) | 0 |
| Subdural haemorrhage | 1/292 (0.3%) | 1 | 0/149 (0%) | 0 |
| Traumatic intracranial haemorrhage | 0/292 (0%) | 0 | 1/149 (0.7%) | 1 |
| Wrist fracture | 0/292 (0%) | 0 | 1/149 (0.7%) | 1 |
| Investigations | ||||
| Alanine aminotransferase increased | 0/292 (0%) | 0 | 1/149 (0.7%) | 1 |
| Aspartate aminotransferase increased | 1/292 (0.3%) | 1 | 0/149 (0%) | 0 |
| Atypical mycobacterium test positive | 1/292 (0.3%) | 1 | 0/149 (0%) | 0 |
| Blood creatinine increased | 1/292 (0.3%) | 1 | 0/149 (0%) | 0 |
| Transaminases increased | 2/292 (0.7%) | 2 | 0/149 (0%) | 0 |
| Metabolism and nutrition disorders | ||||
| Electrolyte imbalance | 1/292 (0.3%) | 1 | 0/149 (0%) | 0 |
| Hypernatraemia | 1/292 (0.3%) | 1 | 0/149 (0%) | 0 |
| Hypokalaemia | 2/292 (0.7%) | 2 | 0/149 (0%) | 0 |
| Tumour lysis syndrome | 2/292 (0.7%) | 2 | 1/149 (0.7%) | 1 |
| Musculoskeletal and connective tissue disorders | ||||
| Back pain | 1/292 (0.3%) | 1 | 0/149 (0%) | 0 |
| Bone pain | 0/292 (0%) | 0 | 1/149 (0.7%) | 1 |
| Soft tissue necrosis | 0/292 (0%) | 0 | 1/149 (0.7%) | 1 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
| Adenocarcinoma gastric | 0/292 (0%) | 0 | 1/149 (0.7%) | 1 |
| Metastatic malignant melanoma | 1/292 (0.3%) | 1 | 0/149 (0%) | 0 |
| Nervous system disorders | ||||
| Ataxia | 1/292 (0.3%) | 1 | 0/149 (0%) | 0 |
| Central nervous system haemorrhage | 1/292 (0.3%) | 1 | 0/149 (0%) | 0 |
| Cerebral haemorrhage | 2/292 (0.7%) | 2 | 2/149 (1.3%) | 2 |
| Cerebrovascular accident | 2/292 (0.7%) | 2 | 0/149 (0%) | 0 |
| Coma | 1/292 (0.3%) | 1 | 0/149 (0%) | 0 |
| Encephalopathy | 1/292 (0.3%) | 1 | 0/149 (0%) | 0 |
| Epilepsy | 2/292 (0.7%) | 2 | 0/149 (0%) | 0 |
| Haemorrhagic stroke | 0/292 (0%) | 0 | 1/149 (0.7%) | 1 |
| Hepatic encephalopathy | 1/292 (0.3%) | 1 | 0/149 (0%) | 0 |
| Intracranial mass | 1/292 (0.3%) | 1 | 0/149 (0%) | 0 |
| Ischaemic stroke | 1/292 (0.3%) | 1 | 0/149 (0%) | 0 |
| Neuropathy peripheral | 1/292 (0.3%) | 1 | 0/149 (0%) | 0 |
| Seizure | 1/292 (0.3%) | 1 | 0/149 (0%) | 0 |
| Subarachnoid haemorrhage | 1/292 (0.3%) | 1 | 0/149 (0%) | 0 |
| Syncope | 1/292 (0.3%) | 1 | 1/149 (0.7%) | 1 |
| Renal and urinary disorders | ||||
| Acute kidney injury | 3/292 (1%) | 3 | 1/149 (0.7%) | 1 |
| Renal failure | 3/292 (1%) | 3 | 0/149 (0%) | 0 |
| Renal tubular acidosis | 1/292 (0.3%) | 1 | 0/149 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||
| Acute respiratory distress syndrome | 1/292 (0.3%) | 1 | 0/149 (0%) | 0 |
| Aspiration | 1/292 (0.3%) | 1 | 0/149 (0%) | 0 |
| Dyspnoea | 1/292 (0.3%) | 1 | 1/149 (0.7%) | 1 |
| Epistaxis | 1/292 (0.3%) | 1 | 1/149 (0.7%) | 1 |
| Pleural effusion | 0/292 (0%) | 0 | 1/149 (0.7%) | 1 |
| Pulmonary embolism | 1/292 (0.3%) | 1 | 0/149 (0%) | 0 |
| Pulmonary haemorrhage | 1/292 (0.3%) | 1 | 0/149 (0%) | 0 |
| Pulmonary oedema | 0/292 (0%) | 0 | 1/149 (0.7%) | 1 |
| Respiratory distress | 0/292 (0%) | 0 | 1/149 (0.7%) | 1 |
| Respiratory failure | 4/292 (1.4%) | 4 | 2/149 (1.3%) | 2 |
| Skin and subcutaneous tissue disorders | ||||
| Erythema | 0/292 (0%) | 0 | 1/149 (0.7%) | 1 |
| Pruritus | 1/292 (0.3%) | 1 | 0/149 (0%) | 0 |
| Rash maculo-papular | 2/292 (0.7%) | 2 | 1/149 (0.7%) | 1 |
| Vascular disorders | ||||
| Embolism | 1/292 (0.3%) | 1 | 1/149 (0.7%) | 1 |
| Hypotension | 5/292 (1.7%) | 7 | 0/149 (0%) | 0 |
| Peripheral artery thrombosis | 1/292 (0.3%) | 1 | 0/149 (0%) | 0 |
| Venoocclusive disease | 1/292 (0.3%) | 1 | 0/149 (0%) | 0 |
Other (Not Including Serious) Adverse Events |
||||
| Idasanutlin-Cytarabine | Placebo-Cytarabine | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 290/292 (99.3%) | 147/149 (98.7%) | ||
| Blood and lymphatic system disorders | ||||
| Anaemia | 79/292 (27.1%) | 131 | 49/149 (32.9%) | 71 |
| Febrile neutropenia | 136/292 (46.6%) | 178 | 63/149 (42.3%) | 79 |
| Neutropenia | 35/292 (12%) | 36 | 13/149 (8.7%) | 19 |
| Thrombocytopenia | 120/292 (41.1%) | 175 | 69/149 (46.3%) | 104 |
| Cardiac disorders | ||||
| Atrial fibrillation | 15/292 (5.1%) | 20 | 6/149 (4%) | 8 |
| Tachycardia | 16/292 (5.5%) | 17 | 3/149 (2%) | 3 |
| Gastrointestinal disorders | ||||
| Abdominal pain | 54/292 (18.5%) | 68 | 18/149 (12.1%) | 19 |
| Abdominal pain upper | 24/292 (8.2%) | 28 | 6/149 (4%) | 6 |
| Constipation | 53/292 (18.2%) | 76 | 76/149 (51%) | 99 |
| Diarrhoea | 251/292 (86%) | 404 | 49/149 (32.9%) | 65 |
| Dry mouth | 15/292 (5.1%) | 15 | 3/149 (2%) | 3 |
| Dyspepsia | 15/292 (5.1%) | 19 | 10/149 (6.7%) | 12 |
| Haemorrhoids | 18/292 (6.2%) | 22 | 8/149 (5.4%) | 8 |
| Nausea | 153/292 (52.4%) | 227 | 47/149 (31.5%) | 56 |
| Stomatitis | 24/292 (8.2%) | 24 | 6/149 (4%) | 8 |
| Vomiting | 89/292 (30.5%) | 145 | 27/149 (18.1%) | 30 |
| General disorders | ||||
| Asthenia | 56/292 (19.2%) | 70 | 19/149 (12.8%) | 24 |
| Chest pain | 19/292 (6.5%) | 25 | 9/149 (6%) | 9 |
| Fatigue | 28/292 (9.6%) | 30 | 13/149 (8.7%) | 15 |
| Mucosal inflammation | 46/292 (15.8%) | 50 | 10/149 (6.7%) | 11 |
| Oedema | 22/292 (7.5%) | 24 | 5/149 (3.4%) | 6 |
| Oedema peripheral | 65/292 (22.3%) | 88 | 26/149 (17.4%) | 34 |
| Pyrexia | 108/292 (37%) | 174 | 49/149 (32.9%) | 67 |
| Hepatobiliary disorders | ||||
| Hyperbilirubinaemia | 52/292 (17.8%) | 56 | 12/149 (8.1%) | 15 |
| Infections and infestations | ||||
| Bacteraemia | 15/292 (5.1%) | 15 | 2/149 (1.3%) | 2 |
| Device related infection | 16/292 (5.5%) | 16 | 8/149 (5.4%) | 8 |
| Oral herpes | 22/292 (7.5%) | 23 | 11/149 (7.4%) | 11 |
| Pneumonia | 18/292 (6.2%) | 18 | 7/149 (4.7%) | 7 |
| Injury, poisoning and procedural complications | ||||
| Fall | 14/292 (4.8%) | 21 | 10/149 (6.7%) | 11 |
| Investigations | ||||
| Alanine aminotransferase increased | 15/292 (5.1%) | 20 | 12/149 (8.1%) | 12 |
| Blood creatinine increased | 10/292 (3.4%) | 12 | 9/149 (6%) | 10 |
| Gamma-glutamyltransferase increased | 15/292 (5.1%) | 16 | 9/149 (6%) | 9 |
| Weight increased | 16/292 (5.5%) | 16 | 6/149 (4%) | 7 |
| Metabolism and nutrition disorders | ||||
| Decreased appetite | 54/292 (18.5%) | 58 | 14/149 (9.4%) | 14 |
| Hyperglycaemia | 17/292 (5.8%) | 23 | 9/149 (6%) | 9 |
| Hypoalbuminaemia | 20/292 (6.8%) | 23 | 4/149 (2.7%) | 4 |
| Hypocalcaemia | 35/292 (12%) | 42 | 7/149 (4.7%) | 9 |
| Hypokalaemia | 129/292 (44.2%) | 207 | 48/149 (32.2%) | 65 |
| Hypomagnesaemia | 51/292 (17.5%) | 72 | 12/149 (8.1%) | 12 |
| Hypophosphataemia | 30/292 (10.3%) | 43 | 11/149 (7.4%) | 15 |
| Musculoskeletal and connective tissue disorders | ||||
| Back pain | 27/292 (9.2%) | 28 | 13/149 (8.7%) | 15 |
| Bone pain | 3/292 (1%) | 3 | 9/149 (6%) | 10 |
| Nervous system disorders | ||||
| Dizziness | 17/292 (5.8%) | 19 | 5/149 (3.4%) | 6 |
| Headache | 49/292 (16.8%) | 67 | 33/149 (22.1%) | 39 |
| Psychiatric disorders | ||||
| Insomnia | 24/292 (8.2%) | 24 | 24/149 (16.1%) | 26 |
| Renal and urinary disorders | ||||
| Haematuria | 17/292 (5.8%) | 26 | 2/149 (1.3%) | 2 |
| Respiratory, thoracic and mediastinal disorders | ||||
| Cough | 40/292 (13.7%) | 45 | 12/149 (8.1%) | 13 |
| Dyspnoea | 28/292 (9.6%) | 34 | 7/149 (4.7%) | 8 |
| Epistaxis | 29/292 (9.9%) | 39 | 26/149 (17.4%) | 37 |
| Hiccups | 15/292 (5.1%) | 17 | 6/149 (4%) | 6 |
| Skin and subcutaneous tissue disorders | ||||
| Erythema | 38/292 (13%) | 44 | 8/149 (5.4%) | 9 |
| Petechiae | 17/292 (5.8%) | 21 | 7/149 (4.7%) | 8 |
| Rash | 55/292 (18.8%) | 62 | 24/149 (16.1%) | 32 |
| Rash maculo-papular | 14/292 (4.8%) | 15 | 8/149 (5.4%) | 9 |
| Vascular disorders | ||||
| Hypertension | 26/292 (8.9%) | 34 | 12/149 (8.1%) | 12 |
| Hypotension | 44/292 (15.1%) | 53 | 16/149 (10.7%) | 16 |
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
Results Point of Contact
| Name/Title | Reference Study ID Number: WO29519 |
|---|---|
| Organization | www.roche.com/about_roche/roche_worldwide.htm |
| Phone | 888-662-6728 (U.S. Only) |
| global-roche-genentech-trials@gene.com |
Responsible Party:
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT02545283
Other Study ID Numbers:
- WO29519
- 2014-003065-15
First Posted:
Sep 9, 2015
Last Update Posted:
Jan 11, 2022
Last Verified:
Dec 1, 2021