Leukemia, Myeloid, AcutePhase 3MIRROSNCT02545283
A Study of Idasanutlin With Cytarabine Versus Cytarabine Plus Placebo in Participants With Relapsed or Refractory Acute Myeloid Leukemia (AML)
A Phase 3 study testing Cytarabine and Idasanutlin in people with Leukemia, Myeloid, Acute, run by Hoffmann-La Roche at 82 sites in 19 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Leukemia, Myeloid, Acute
- What is being tested?
- Cytarabine and Idasanutlin
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 447 participants
- Where
- 82 sitesin 19 countries
- Study dates
- 30 Dec 2015to 24 Apr 2020
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
Who cannot join
- 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
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- 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
Trial locations and contacts
82 sites in 19 countries.
82 sites in 19 countries
Italy14 sites
ASST PAPA GIOVANNI XXIII; Ematologia
Bergamo, Lombardy, 24127
Az. Osp. S. Orsola Malpighi; Istituto Di Oncologia Seragnoli
Bologna, Emilia-Romagna, 40138
Az. Osp. Di Careggi; Divisione Di Ematologia
Florence, Tuscany, 50135
IRCCS AOU S.Martino; Clinica Ematologica
Genoa, Liguria, 16132
Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST); Onco-Ematologia
Meldola, Emilia-Romagna, 47014
Ospedale San Raffaele, IRCCS
Milan, Lombardy, 20132
Asst Grande Ospedale Metropolitano Niguarda; Dipartimento Di Ematologia Ed Oncologia
Milan, Lombardy, 20162
Ospedale Cardarelli; Divisione Di Ematologia
Naples, Campania, 80131
A.O. Universitaria San Luigi Gonzaga di Orbassano; Ambulatorio per le Malattie Rare del Polmone
Orbassano (TO), Piedmont, 10043
Ospedale Santa Chiara; Unita Operativa Di Ematologia
Pisa, Tuscany, 56100
Az. Osp. S. Maria Delle Croci; U.O. Di Ematologia
Ravenna, Emilia-Romagna, 48100
Az. Osp. Uni Ria Policlinico Tor Vergata; Unita Di Ematologia
Rome, Lazio, 00133
A.O.U. Citta' Della Salute E Della Scienza-P.O. Molinette;S.C. Ematologia
Turin, Piedmont, 10126
A.O. Universitaria S. Maria Della Misericordia Di Udine; Oncologia; Clinica Ematologica
Udine, Friuli Venezia Giulia, 33100
France10 sites
Centre Hospitalier Uni Ire; Service Des Maladies Du Sang
Angers, 49933
Hopital Claude Huriez; Hematologie
Lille, 59037
Institut J Paoli I Calmettes; Onco Hematologie 2
Marseille, 13273
Hopital Hotel Dieu Et Hme;Hopital De Jour
Nantes, 44093
Hopital Saint Louis; Oncologie Medicale
Paris, 75475
HOPITAL SAINT ANTOINE;Hematologie Clinique
Paris, 75571
Hopital De Haut Leveque; Hematologie Clinique
Pessac, 33604
Centre Hospitalier Lyon Sud; Hematolgie
Pierre-Bénite, 69495
IUCT Oncopole; Hematologie
Toulouse, 31059
Hopitaux De Brabois; Hematologie Medecine Interne
Vandœuvre-lès-Nancy, 54511
Germany9 sites
Uniklinik RWTH Aachen; Klinik IV; Klinik Hämatologie, Onkologie, Hämostaseologie und Stamm.
Aachen, 52074
Universitätsklinikum Bonn; Med. Klinik und Poliklinik III; Hämatologie, Onkologie und Rheumatologie
Bonn, 53127
Klinikum Braunschweig; Medizinische Klinik III; Klinik für Hämatologie und Onkologie
Braunschweig, 38114
Klinikum Chemnitz gGmbH Krankenhaus Küchwald Klinik f.Innere Medizin III
Chemnitz, 09113
Klinik der Uni zu Köln; I. Med. Klinik
Cologne, 50937
Universitätsklinikum "Carl Gustav Carus"; Medizinische Klinik und Poliklinik I
Dresden, 01307
Medizinische Hochschule Hannover; Zentrum Innere Medizin; Abt. Hämatologie u. Onkologie
Hanover, 30625
Uni. der Johannes Gutenberg-Universitaet Mainz; III. Medizinische Klinik und Poliklinik
Mainz, 55131
Universitätsklinikum Marburg Zentrum f. Innere Medizin
Marburg, 35043
United States7 sites
Baylor University Medical Center
Dallas, Texas, 75204
Northwell Health
Great Neck, New York, 11021
New York Medical College
Hawthorne, New York, 10532
M.D. Anderson Cancer Center; Department of Hematology
Houston, Texas, 77030
Ichan School of Medicine at Mount Sinai
New York, New York, 10029
Abramson Cancer Center; Univ of Pennsylvania
Philadelphia, Pennsylvania, 19104
Thomas Jefferson University
Philadelphia, Pennsylvania, 19107
Australia5 sites
Royal Adelaide Hospital; Haematology Clinical Trials
Adelaide, South Australia, 5000
Canberra Hospital; Haematology Department
Canberra, Australian Capital Territory, 2605
Geelong Hospital; Andrew Love Cancer Centre
Geelong, Victoria, 3220
Alfred Hospital; Clinical Haematology and Bone Marrow Transplantation
Melbourne, Victoria, 3004
Concord Repatriation General Hospital; Haematology
Sydney, New South Wales, 2139
South Korea5 sites
Pusan National University Hospital
Busan, 49241
Chonnam National University Hwasun Hospital
Jeollanam-do, 58128
Seoul National University Hospital
Seoul, 03080
Samsung Medical Center
Seoul, 06351
Seoul St Mary's Hospital
Seoul, 06591
Spain5 sites
Hospital de la Santa Creu i Sant Pau; Servicio de Hematologia
Barcelona, 08025
Hospital Clínic i Provincial; Servicio de Hematología y Oncología
Barcelona, 08036
Hospital Univ. 12 de Octubre; Servicio de Hematologia
Madrid, 28041
Hospital Universitario Virgen del Rocio
Seville, 41013
Hospital Universitario la Fe; Servicio de Hematologia
Valencia, 46026
United Kingdom5 sites
Birmingham Heartlands Hospital
Birmingham, B9 5SS
University Hospital of Wales
Cardiff, CF14 4XW
St Bartholomew's Hospital
London, EC1M 6BQ
Christie Hospital NHS Trust
Manchester, M20 4BX
Royal Marsden NHS Foundation Trust
Sutton, SM2 5PT
Israel4 sites
Shaare Zedek Medical Center; Hematology Dept.
Jerusalem, 9103102
Hadassah Ein Karem Hospital; Haematology
Jerusalem, 9112001
Rabin Medical Center-Beilinson Campus;Hematology-Oncology
Petah Tikva, 4941492
Ichilov Sourasky Medical Center; Heamatology
Tel Aviv, 6423906
Belgium3 sites
CH Jolimont - Lobbes (Jolimont)
Haine-Saint-Paul, 7100
CHU Sart-Tilman
Liège, 4000
AZ Delta (Campus Rumbeke)
Roeselare, 8800
Russia3 sites
"Hematological Scientific Center
Moscow, 125167
St. Petersburg State Medical University n.a. I.P. Pavlov; Hematology, transfusiology and transplanta
Saint Petersburg, 197022
FGBU "Federal Medical and Research Center named after V.A.Almazov" Russian Ministry of Health
Saint Petersburg, 197341
Finland2 sites
Helsinki University Central Hospital; Hematology
Helsinki, 00290
Tampere University Hospital; Hematology
Tampere, 33521
Netherlands2 sites
Academisch Medisch Centrum; Hematologie
Amsterdam, 1105 AZ
Academisch Ziekenhuis Maastricht
Maastricht, 6202 AZ
Norway2 sites
Haukeland Universitetssjukehus; Klinisk forskningspost
Bergen, 5021
Oslo Universitetssykehus HF, Rikshospitalet
Oslo, 0372
Switzerland2 sites
Universitätsspital Basel; Hämatologie
Basel, 4031
Universitätsspital Zürich Medizin Hämatologie; Klinik für Hämatologie
Zurich, 8091
Canada1 site
Juravinski Cancer Clinic; Clinical Trials Department
Hamilton, Ontario, L8V 5C2
New Zealand1 site
Auckland city hospital; Auckland Regional Cancer Centre and Blood Service
Auckland, 1023
Panama1 site
Complejo Hospitalario Arnulfo Arias Madrid; Servicio de Hematología
Panama City, 0824
About this study
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)
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.
- Conditions
- Leukemia, Myeloid, Acute
- Being tested
- Cytarabine, Idasanutlin, Placebo
- Medical subject headings
- Leukemia, Myeloid, Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CytarabineDrug
Participants will receive cytarabine 1 gram per square meter (g/m^2) intravenous (IV) infusion for 5 days of every treatment cycle.
IdasanutlinDrug
Also called RG7388
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.
PlaceboOther
Participants will receive idasanutlin matching placebo PO BID or QD for 5 days of every treatment cycle.
| Study group | Role | What they receive |
|---|---|---|
| Idasanutlin plus Cytarabine | Experimental | 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. Receives: Drug: Cytarabine; Drug: Idasanutlin |
| Placebo plus Cytarabine | Placebo comparator | 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. Receives: Drug: Cytarabine; Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Survival in TP53 WT Population
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.
Measured: From randomization to death from any cause (up to approximately 4.5 years)
Secondary outcomes (34)
Percentage of Participants in Complete Response (CR) at the End of Induction According to Hematologic Malignancy Response Assessment (HMRA) in TP53 WT Population
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.
Measured: At the end of induction (up to Day 56)
Event-Free Survival (EFS) According to HMRA in TP53 WT Population
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.
Measured: From randomization up to treatment failure, relapse, or death from any cause (up to approximately 4.5 years)
Percentage of Participants With Overall Remission (CR, CRp, and CRi) at the End of Induction According to HMRA in TP53 WT Population
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.
Measured: At the end of induction (up to Day 56)
Duration of Remission Following CR (DOR) in TP53 WT Population
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.
Measured: From achieving CR until relapse or death from any cause (up to approximately 4.5 years)
Percentage of Participants Undergoing HSCT Following Complete Response (CR), in TP53 WT Population
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.
Measured: Baseline up to approximately 4.5 years
Percentage of Participants With Complete Response (CR) in Clinically Actionable Mutation-Defined Subpopulation (FLT3, IDH1 and IDH2) in TP53 WT Population
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.
Measured: At the end of induction (up to Day 56)
Overall Survival in Clinically Actionable Mutation-Defined Subpopulation (FLT3, IDH1 and IDH2) in TP53 WT Population
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.
Measured: From randomization to death from any cause (up to approximately 4.5 years)
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)
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.
Measured: Baseline up to approximately 4.5 years
Number of Participants With Adverse Events Leading to Discontinuation
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.
Measured: Baseline up to approximately 4.5 years
Number of Participants With Adverse Events Leading to Death up to Day 30
The number of participants with AE resulted by death within 30 days from dosing is reported
Measured: Up to Day 30
Number of Participants With Adverse Events Leading to Death up to Day 60
The number of participants with AE resulted by death within 60 days from dosing is reported
Measured: Up to Day 60
Number of Participants With Clinical Laboratory Abnormalities in Biochemistry Tests at the Greatest Severity, According to NCI-CTCAE v4.03
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.
Measured: Up to Approximately 4.5 Years
Number of Participants With Clinical Laboratory Abnormalities in Hematology Tests at the Greatest Severity, According to NCI-CTCAE v4.03
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.
Measured: Up to Approximately 4.5 Years
Change From Baseline in Body Temperature Over Time
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.
Measured: 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)
Change From Baseline in Systolic Blood Pressure Over Time
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.
Measured: 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)
Change From Baseline in Diastolic Blood Pressure Over Time
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.
Measured: 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)
Change From Baseline in Pulse Rate Over Time
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.
Measured: 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)
Change From Baseline in Respiratory Rate Over Time
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.
Measured: Up to Approximately 4.5 Years
Change From Baseline in Heart Rate, as Measured by Electrocardiogram
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.
Measured: 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
Change From Baseline in Electrocardiogram Parameters: PQ, PR, RR, QRS, QT and QTcF Intervals
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.
Measured: 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)
Total Duration of Study Treatment
Participants were planned to be treated up to 3 Cycles.
Measured: Up to 3 cycles (1 cycle is 28 days)
Number of Treatment Cycles Started
Participants who started the study treatment cycles are reported.
Measured: Up to 3 cycles (1 cycle is 28 days)
Cumulative Dose of Idasanutlin and Cytarabine
The cumulative doses of idasanutlin and cytaradine are reported.
Measured: Up to 3 cycles (1 cycle is 28 days)
Apparent Clearance (CL/F) of Idasanutlin
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.
Measured: 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 Volume of Distribution (Vd/F) of Idasanutlin
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.
Measured: 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
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.
Measured: 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
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.
Measured: 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
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.
Measured: 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
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.
Measured: 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
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.
Measured: 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)
Total Clearance (CL) of Cytarabine
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.
Measured: 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)
Volume of Distribution (Vd) of Cytarabine
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.
Measured: 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)
Change From Baseline in European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Score
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.
Measured: 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)
Change From Baseline in EuroQol 5 Dimension 5-Level (EQ-5D-5L) Questionnaire Score
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.
Measured: 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)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Sep 2015 (estimated)
- Study start30 Dec 2015
- Primary completion24 Apr 2020
- Study completion24 Apr 2020
Why it stopped: The study was stopped for futility based on efficacy results at the interim analysis; no unexpected safety findings were observed.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Leukemia, Myeloid, AcuteStudies of the same condition, open and under way.
- More trials run by Hoffmann-La RocheThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 447 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hoffmann-La Roche
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Trials, Study director, Hoffmann-La Roche
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02545283
- Sponsor's protocol ID
- WO29519
- Other IDs
- 2014-003065-15, 2014
- Acronym
- MIRROS
- Status last verified
- Dec 2021
- First submitted
- 31 Aug 2015
- Last updated
- 11 Jan 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Montesinos P, Beckermann BM, Catalani O, Esteve J, Gamel K, Konopleva MY, Martinelli G, Monnet A, Papayannidis C, Park A, Recher C, Rodriguez-Veiga R, Rollig C, Vey N, Wei AH, Yoon SS, Fenaux P. MIRROS: a randomized, placebo-controlled, Phase III trial of cytarabine +/- idasanutlin in relapsed or refractory acute myeloid leukemia. Future Oncol. 2020 May;16(13):807-815. doi: 10.2217/fon-2020-0044. Epub 2020 Mar 13.
PubMed 32167393
Study at a glance
From the registry record, last updated by the sponsor on 11 Jan 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT02545283
- Acronym / sponsor ID
- MIRROS / WO29519
- Conditions
- Leukemia, Myeloid, Acute
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The study was stopped for futility based on efficacy results at the interim analysis; no unexpected safety findings were observed.
- Enrolment
- 447 participants (actual)
- Lead sponsor
- Hoffmann-La RocheIndustry (pharma, biotech, devices)
- Study start
- 30 Dec 2015 (actual)
- Primary completion
- 24 Apr 2020 (actual)
- Study completion
- 24 Apr 2020 (actual)
- First posted
- 9 Sep 2015 (estimated)
- Results
- Posted 14 Sep 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Idasanutlin plus Cytarabine | Experimental | Drug: Cytarabine, Drug: IdasanutlinParticipants 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. |
| Placebo plus Cytarabine | Placebo comparator | Drug: Cytarabine, Other: PlaceboParticipants 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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)
Key exclusion criteria (12 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CytarabineParticipants will receive cytarabine 1 gram per square meter (g/m^2) intravenous (IV) infusion for 5 days of every treatment cycle. | Drug | Idasanutlin plus Cytarabine, Placebo plus Cytarabine |
| IdasanutlinAlso: RG7388Participants 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. | Drug | Idasanutlin plus Cytarabine |
| PlaceboParticipants will receive idasanutlin matching placebo PO BID or QD for 5 days of every treatment cycle. | Other | Placebo plus Cytarabine |
Primary outcome
Overall Survival in TP53 WT Population
Time frame: 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.
34 secondary outcomes
Percentage of Participants in Complete Response (CR) at the End of Induction According to Hematologic Malignancy Response Assessment (HMRA) in TP53 WT Population
Time frame: At the end of induction (up to Day 56)
Event-Free Survival (EFS) According to HMRA in TP53 WT Population
Time frame: From randomization up to treatment failure, relapse, or death from any cause (up to approximately 4.5 years)
Percentage of Participants With Overall Remission (CR, CRp, and CRi) at the End of Induction According to HMRA in TP53 WT Population
Time frame: At the end of induction (up to Day 56)
Duration of Remission Following CR (DOR) in TP53 WT Population
Time frame: From achieving CR until relapse or death from any cause (up to approximately 4.5 years)
Percentage of Participants Undergoing HSCT Following Complete Response (CR), in TP53 WT Population
Time frame: Baseline up to approximately 4.5 years
Percentage of Participants With Complete Response (CR) in Clinically Actionable Mutation-Defined Subpopulation (FLT3, IDH1 and IDH2) in TP53 WT Population
Time frame: At the end of induction (up to Day 56)
Overall Survival in Clinically Actionable Mutation-Defined Subpopulation (FLT3, IDH1 and IDH2) in TP53 WT Population
Time frame: From randomization to death from any cause (up to approximately 4.5 years)
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)
Time frame: Baseline up to approximately 4.5 years
Number of Participants With Adverse Events Leading to Discontinuation
Time frame: Baseline up to approximately 4.5 years
Number of Participants With Adverse Events Leading to Death up to Day 30
Time frame: Up to Day 30
Number of Participants With Adverse Events Leading to Death up to Day 60
Time frame: Up to Day 60
Number of Participants With Clinical Laboratory Abnormalities in Biochemistry Tests at the Greatest Severity, According to NCI-CTCAE v4.03
Time frame: Up to Approximately 4.5 Years
Number of Participants With Clinical Laboratory Abnormalities in Hematology Tests at the Greatest Severity, According to NCI-CTCAE v4.03
Time frame: Up to Approximately 4.5 Years
Change From Baseline in Body Temperature Over Time
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)
Change From Baseline in Systolic Blood Pressure Over Time
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)
Change From Baseline in Diastolic Blood Pressure Over Time
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)
Change From Baseline in Pulse Rate Over Time
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)
Change From Baseline in Respiratory Rate Over Time
Time frame: Up to Approximately 4.5 Years
Change From Baseline in Heart Rate, as Measured by Electrocardiogram
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
Change From Baseline in Electrocardiogram Parameters: PQ, PR, RR, QRS, QT and QTcF Intervals
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)
Total Duration of Study Treatment
Time frame: Up to 3 cycles (1 cycle is 28 days)
Number of Treatment Cycles Started
Time frame: Up to 3 cycles (1 cycle is 28 days)
Cumulative Dose of Idasanutlin and Cytarabine
Time frame: Up to 3 cycles (1 cycle is 28 days)
Apparent Clearance (CL/F) of Idasanutlin
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)
Apparent Volume of Distribution (Vd/F) of Idasanutlin
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)
Maximum Concentration Observed (Cmax) of Idasanutlin
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)
Steady-State Concentration (Ctrough) of Idasanutlin
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)
Area Under the Concentration-Time Curve (AUC) During One Dosing Interval (AUCtau) of Idasanutlin
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)
AUC From Time Zero to 24 Hours Post Dose (AUC0-24) of Idasanutlin
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)
Half-Life (t 1/2) of Idasanutlin
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)
Total Clearance (CL) of Cytarabine
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)
Volume of Distribution (Vd) of Cytarabine
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)
Change From Baseline in European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Score
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)
Change From Baseline in EuroQol 5 Dimension 5-Level (EQ-5D-5L) Questionnaire Score
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)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Jan 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 32167393Montesinos P, Beckermann BM, Catalani O, Esteve J, Gamel K, Konopleva MY, Martinelli G, Monnet A, Papayannidis C, Park A, Recher C, Rodriguez-Veiga R, Rollig C, Vey N, Wei AH, Yoon SS, Fenaux P. MIRROS: a randomized, placebo-controlled, Phase III trial of cytarabine +/- idasanutlin in relapsed or refractory acute myeloid leukemia. Future Oncol. 2020 May;16(13):807-815. doi: 10.2217/fon-2020-0044. Epub 2020 Mar 13.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Clinical Trials study director
Hoffmann-La Roche
82 sites in 19 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Cytarabine and Idasanutlin in people with Leukemia, Myeloid, Acute, run by Hoffmann-La Roche at 82 sites in 19 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 11 Jan 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 82 sites in Italy, France, Germany, United States, Australia and 14 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 14 Sep 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall Survival in TP53 WT Population (time frame: From randomization to death from any cause (up to approximately 4.5 years)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02545283, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Jan 2022.