A Global Study of the Efficacy and Safety of Midostaurin + Chemotherapy in Newly Diagnosed Patients With FLT3 Mutation Negative (FLT3-MN) Acute Myeloid Leukemia (AML)

A Phase III, Randomized, Double-blind Study of Chemotherapy With Daunorubicin or Idarubicin and Cytarabine for Induction and Intermediate Dose Cytarabine for Consolidation Plus Midostaurin (PKC412) or Chemotherapy Plus Placebo in Newly Diagnosed Patients With FLT-3 Mutation Negative Acute Myeloid Leukemia (AML)

The purpose of this study was to confirm the preliminary evidence from early clinical trials that midostaurin may provide clinical benefit not only to AML patients with the FLT3-mutations but also in FLT3-MN (SR<0.05) AML (FLT3 mutant to wild type signal ratio below the 0.05 clinical cut-off).

This study evaluated the efficacy and safety of midostaurin in combination with daunorubicin or idarubicin and cytarabine for induction and intermediate-dose cytarabine for consolidation, and midostaurin single agent post-consolidation therapy in newly diagnosed patients with FLT3-MN (SR<0.05) AML.

Study Overview

• Status: Completed
• Conditions: Acute Myeloid Leukemia (AML)
• Intervention / Treatment: Drug: Midostaurin; Drug: Chemotherapy; Drug: Placebo

Detailed Description

This was a multi-center, multinational, randomized, double-blind Phase III study using a group sequential design. Subjects were stratified according to age (<60 vs. ≥ 60 years). Subjects within each stratum were randomized in a 1:1 ratio into one of two treatment arms: Midostaurin + chemotherapy 'or' Placebo + chemotherapy.

The study consisted of the following phases:

Screening/randomization phase: Subjects had to sign informed consent form before screening for enrollment. Subjects started chemotherapy at day 1 and were randomized at day 8.

Induction phase: All subjects received at least one cycle (28 days) of induction therapy with continuous infusion cytarabine (D1 - D7) and daunorubicin or idarubicin (D1 - D3) (induction 1). Subjects who did not achieve CR or CRi with adequate blood count recovery after Induction 1 received a second cycle with intermediate-dose cytarabine (D1 - D3) and daunorubicin or idarubicin (D1 - D3) (induction 2). Subjects who did not achieve CR or CRi with adequate blood recovery after induction 2 discontinued study treatment and were followed for survival.

Consolidation phase: Subjects who achieved CR or CRi with adequate blood count recovery after induction with one or two cycles of induction proceeded to consolidation therapy with either 3 or 4 cycles respectively of intermediate-dose cytarabine (D1 - D3), or to Hematopoietic Stem Cells Transplantation (HSCT) with or without preceding consolidation cycles.

Post-consolidation phase: Subjects who maintained CR or CRi with adequate blood count recovery at the end of the consolidation phase received 12 cycles (28 days/cycle) of continuous therapy with midostaurin or placebo twice daily at 50 mg. Subjects who underwent HSCT after achieving CR or CRi with adequate blood count recovery received midostaurin or placebo twice daily 50 mg post-transplant therapy, continuously, for up to 12 cycles (28 days/cycle). Post HSCT post-consolidation therapy began >30 days but not later than 100 days following HSCT.

Follow-up phase: All enrolled subjects were followed through the treatment period and until relapse/treatment failure, thereafter for start of new line of therapy and survival.

• Study Type: Interventional
• Enrollment (Actual): 511
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires
    • Caba, Buenos Aires, Argentina, C1118AAT
      • Novartis Investigative Site
• Australia
  • New South Wales
    • Westmead, New South Wales, Australia, 2145
      • Novartis Investigative Site
  • Queensland
    • Woolloongabba, Queensland, Australia, 4102
      • Novartis Investigative Site
  • Victoria
    • Prahran, Victoria, Australia, 3181
      • Novartis Investigative Site
  • Western Australia
    • Murdoch, Western Australia, Australia, 6150
      • Novartis Investigative Site
• Austria
  • Linz, Austria, A-4010
    • Novartis Investigative Site
  • Vienna, Austria, 1140
    • Novartis Investigative Site
  • Wien, Austria, 1090
    • Novartis Investigative Site
• Belgium
  • Antwerpen, Belgium, 2060
    • Novartis Investigative Site
  • Brugge, Belgium, 8000
    • Novartis Investigative Site
  • Roeselare, Belgium, 8800
    • Novartis Investigative Site
• Brazil
  • Sao Paulo, Brazil, 01221 900
    • Novartis Investigative Site
  • RS
    • Porto Alegre, RS, Brazil, 90035-003
      • Novartis Investigative Site
  • SP
    • Sao Paulo, SP, Brazil, 04014-002
      • Novartis Investigative Site
• Bulgaria
  • Sofia, Bulgaria, 1756
    • Novartis Investigative Site
• Czechia
  • Brno - Bohunice, Czechia, 625 00
    • Novartis Investigative Site
  • Plzen-Bory, Czechia, 30599
    • Novartis Investigative Site
• France
  • Angers Cedex 1, France, 49033
    • Novartis Investigative Site
  • Avignon, France, 84000
    • Novartis Investigative Site
  • Dijon, France, 21034
    • Novartis Investigative Site
  • Lille Cedex, France, 59037
    • Novartis Investigative Site
  • Nantes Cedex 1, France, 44093
    • Novartis Investigative Site
  • Paris, France, 75012
    • Novartis Investigative Site
  • Pierre Benite, France, 69495
    • Novartis Investigative Site
  • Toulouse, France, 31059
    • Novartis Investigative Site
  • Bayonne Cedex
    • Bayonne, Bayonne Cedex, France, 64109
      • Novartis Investigative Site
• Germany
  • Bad Saarow, Germany, 15526
    • Novartis Investigative Site
  • Berlin, Germany, 13125
    • Novartis Investigative Site
  • Berlin, Germany, 10967
    • Novartis Investigative Site
  • Berlin, Germany, 13353
    • Novartis Investigative Site
  • Berlin, Germany, 12351
    • Novartis Investigative Site
  • Bochum, Germany, 44892
    • Novartis Investigative Site
  • Bonn, Germany, 53105
    • Novartis Investigative Site
  • Braunschweig, Germany, 38114
    • Novartis Investigative Site
  • Darmstadt, Germany, 64283
    • Novartis Investigative Site
  • Duesseldorf, Germany, 40225
    • Novartis Investigative Site
  • Duisburg, Germany, 47166
    • Novartis Investigative Site
  • Eschweiler, Germany, 52249
    • Novartis Investigative Site
  • Essen Werden, Germany, 45239
    • Novartis Investigative Site
  • Flensburg, Germany, 24939
    • Novartis Investigative Site
  • Giessen, Germany, 35392
    • Novartis Investigative Site
  • Gottingen, Germany, 37075
    • Novartis Investigative Site
  • Hamburg, Germany, 20246
    • Novartis Investigative Site
  • Hamburg, Germany, 20099
    • Novartis Investigative Site
  • Hannover, Germany, 30625
    • Novartis Investigative Site
  • Homburg, Germany, 66421
    • Novartis Investigative Site
  • Karlsruhe, Germany, 76133
    • Novartis Investigative Site
  • Kiel, Germany, 24116
    • Novartis Investigative Site
  • Leipzig, Germany, 04103
    • Novartis Investigative Site
  • Luebeck, Germany, 23538
    • Novartis Investigative Site
  • Magdeburg, Germany, 39120
    • Novartis Investigative Site
  • Mainz, Germany, 55131
    • Novartis Investigative Site
  • Muenchen, Germany, 80377
    • Novartis Investigative Site
  • Osnabrueck, Germany, 49076
    • Novartis Investigative Site
  • Paderborn, Germany, 33098
    • Novartis Investigative Site
  • Rostock, Germany, 18057
    • Novartis Investigative Site
  • Siegen, Germany, 57072
    • Novartis Investigative Site
  • Stuttgart, Germany, 70376
    • Novartis Investigative Site
  • Stuttgart, Germany, 70176
    • Novartis Investigative Site
  • Ulm, Germany, 89081
    • Novartis Investigative Site
  • Wuerzburg, Germany, 97080
    • Novartis Investigative Site
  • Zwickau, Germany, 08060
    • Novartis Investigative Site
  • Bavaria
    • Regensburg, Bavaria, Germany, 93053
      • Novartis Investigative Site
  • Brandenburg
    • Schwerin, Brandenburg, Germany, 19049
      • Novartis Investigative Site
• Israel
  • Haifa, Israel, 3109601
    • Novartis Investigative Site
  • Petach Tikva, Israel, 4941492
    • Novartis Investigative Site
  • Tel Aviv, Israel, 6423906
    • Novartis Investigative Site
• Italy
  • AL
    • Alessandria, AL, Italy, 15100
      • Novartis Investigative Site
  • AN
    • Ancona, AN, Italy, 60126
      • Novartis Investigative Site
  • BG
    • Bergamo, BG, Italy, 24127
      • Novartis Investigative Site
  • BS
    • Brescia, BS, Italy, 25123
      • Novartis Investigative Site
  • CT
    • Catania, CT, Italy, 95123
      • Novartis Investigative Site
  • MI
    • Milano, MI, Italy, 20162
      • Novartis Investigative Site
  • MO
    • Modena, MO, Italy, 41124
      • Novartis Investigative Site
  • PA
    • Palermo, PA, Italy, 90146
      • Novartis Investigative Site
  • PC
    • Piacenza, PC, Italy, 29100
      • Novartis Investigative Site
  • PE
    • Pescara, PE, Italy, 65124
      • Novartis Investigative Site
  • PG
    • Perugia, PG, Italy, 06129
      • Novartis Investigative Site
  • RC
    • Reggio Calabria, RC, Italy, 89124
      • Novartis Investigative Site
  • RM
    • Roma, RM, Italy, 00168
      • Novartis Investigative Site
    • Roma, RM, Italy, 00161
      • Novartis Investigative Site
    • Roma, RM, Italy, 00133
      • Novartis Investigative Site
  • TA
    • Taranto, TA, Italy, 74100
      • Novartis Investigative Site
  • TO
    • Torino, TO, Italy, 10126
      • Novartis Investigative Site
  • VI
    • Vicenza, VI, Italy, 36100
      • Novartis Investigative Site
• Japan
  • Aomori, Japan, 030 8553
    • Novartis Investigative Site
  • Kyoto, Japan, 606 8507
    • Novartis Investigative Site
  • Osaka, Japan, 534-0021
    • Novartis Investigative Site
  • Yamagata, Japan, 990 9585
    • Novartis Investigative Site
  • Aichi
    • Nagoya-city, Aichi, Japan, 466-8650
      • Novartis Investigative Site
  • Ehime
    • Matsuyama-city, Ehime, Japan, 790-8524
      • Novartis Investigative Site
  • Fukuoka
    • Fukuoka city, Fukuoka, Japan, 812-8582
      • Novartis Investigative Site
  • Fukushima
    • Fukushima city, Fukushima, Japan, 960 1295
      • Novartis Investigative Site
  • Gifu
    • Gifu shi, Gifu, Japan, 500 8513
      • Novartis Investigative Site
  • Hiroshima
    • Fukuyama, Hiroshima, Japan, 720-0001
      • Novartis Investigative Site
  • Ibaraki
    • Tsukuba city, Ibaraki, Japan, 305-8576
      • Novartis Investigative Site
  • Kanagawa
    • Isehara, Kanagawa, Japan, 259-1193
      • Novartis Investigative Site
  • Nagasaki
    • Nagasaki-city, Nagasaki, Japan, 852-8501
      • Novartis Investigative Site
  • Okayama
    • Okayama city, Okayama, Japan, 701-1192
      • Novartis Investigative Site
  • Osaka
    • Hirakata-city, Osaka, Japan, 573-1191
      • Novartis Investigative Site
    • Osaka Sayama, Osaka, Japan, 589 8511
      • Novartis Investigative Site
  • Shizuoka
    • Hamamatsu, Shizuoka, Japan, 432-8580
      • Novartis Investigative Site
  • Tochigi
    • Shimotsuke, Tochigi, Japan, 329-0498
      • Novartis Investigative Site
  • Tokyo
    • Bunkyo ku, Tokyo, Japan, 113-8677
      • Novartis Investigative Site
    • Bunkyo-ku, Tokyo, Japan, 113-8603
      • Novartis Investigative Site
• Norway
  • Bergen, Norway, NO-5021
    • Novartis Investigative Site
  • Oslo, Norway, 0424
    • Novartis Investigative Site
• Poland
  • Gdansk, Poland, 80 952
    • Novartis Investigative Site
• Portugal
  • Lisboa, Portugal, 1099 023
    • Novartis Investigative Site
  • Porto, Portugal, 4200-072
    • Novartis Investigative Site
• Spain
  • Barcelona, Spain, 08041
    • Novartis Investigative Site
  • Madrid, Spain, 28041
    • Novartis Investigative Site
  • Madrid, Spain, 28034
    • Novartis Investigative Site
  • Valencia, Spain, 46026
    • Novartis Investigative Site
  • Zaragoza, Spain, 50009
    • Novartis Investigative Site
  • Andalucia
    • Cordoba, Andalucia, Spain, 14004
      • Novartis Investigative Site
    • Sevilla, Andalucia, Spain, 41013
      • Novartis Investigative Site
  • Castilla Y Leon
    • Salamanca, Castilla Y Leon, Spain, 37007
      • Novartis Investigative Site
  • Catalunya
    • Hospitalet de LLobregat, Catalunya, Spain, 08907
      • Novartis Investigative Site
  • Extremadura
    • Caceres, Extremadura, Spain, 10003
      • Novartis Investigative Site
  • Pais Vasco
    • Barakaldo, Pais Vasco, Spain, 48903
      • Novartis Investigative Site
• Switzerland
  • Bern, Switzerland, 3010
    • Novartis Investigative Site
  • Zurich, Switzerland, 8091
    • Novartis Investigative Site
• Taiwan
  • Kaohsiung City, Taiwan, 83301
    • Novartis Investigative Site
  • Taipei, Taiwan, 10002
    • Novartis Investigative Site
  • Chiayi Hsien
    • Putzu City, Chiayi Hsien, Taiwan, 61363
      • Novartis Investigative Site
  • Taoyuan Taiwan ROC
    • Kuei Shan Chiang, Taoyuan Taiwan ROC, Taiwan, 33305
      • Novartis Investigative Site
• Turkey
  • Adana, Turkey, 01330
    • Novartis Investigative Site
  • Ankara, Turkey, 06100
    • Novartis Investigative Site
  • Aydin, Turkey, 09100
    • Novartis Investigative Site
• United States
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago Medical Center .
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Dana Farber Cancer Institute
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health and Science Univ

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Diagnosis of AML (≥20% blasts in the bone marrow based on WHO 2016 classification). Patients with APL with PML-RARA are not eligible.
2. Suitability for intensive induction chemotherapy in the judgment of the investigator
3. Documented absence of an ITD and TKD activating mutation at codons D835 and I836 in the FLT3 gene, as determined by analysis in a Novartis designated laboratory using a validated clinical trial assay with clinical cutoff of 0.05 mutant to wild type signal ratio
4. Age ≥18 years
5. Laboratory values that indicate adequate organ function assessed locally at the screening visit

Exclusion Criteria:

1. Central nervous system (CNS) leukemia
2. Therapy-related secondary AML
3. Isolated extramedullary leukemia
4. Prior therapy for leukemia or myelodysplasia
5. AML after antecedent myelodysplasia (MDS) with prior cytotoxic treatment (e.g., azacytidine or decitabine)
6. Prior treatment with a FLT3 inhibitor (e.g., midostaurin, quizartinib, sorafenib)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Midostaurin + chemotherapy; Participants received Midostaurin in Induction 50mg twice daily on Day 8 until 48 hrs before start of next cycle. During Induction 2 and consolidation 50mg twice daily on Day 4 until 48 hrs before start of next cycle. During post-consolidation 50mg twice daily for 28 consecutive days of each 28-day treatment cycle up to 12 cycles. For participants who could not tolerate the protocol-specified dosing schedule, dose interruptions and/or reductions were either recommended or mandated allowing participants to continue the study treatment. Chemotherapy consisted of daunorubicin or idarubicin and cytarabine for induction and intermediate dose cytarabine for consolidation.	Drug: Midostaurin; Midostaurin was provided as 25 mg capsules 8PC, was supplied as double-blind in blister packs and taken orally.; Other Names: PKC412; Drug: Chemotherapy; Along with the study drug/placebo, chemotherapy was given as well: either Daunorubicin or Idarubicin and Cytarabine - all taken by i.v.
Placebo Comparator: Placebo + chemotherapy; Participants received matching placebo to midostaurin with same dose, plus chemotherapy. Chemotherapy consisted of daunorubicin or idarubicin and cytarabine for induction and intermediate dose cytarabine for consolidation	Drug: Chemotherapy; Along with the study drug/placebo, chemotherapy was given as well: either Daunorubicin or Idarubicin and Cytarabine - all taken by i.v.; Drug: Placebo; Placebo was provided as 25 mg soft gelatin capsules 8PC, was supplied as double-blind in blister packs and taken orally.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Event Free Survival (EFS)	EFS was defined as the time from randomization to failure to obtain a complete remission (CR) or Complete remission with incomplete hematologic recovery (CRi) with adequate blood count recovery in induction, relapse after CR or CRi with adequate blood count recovery or death due to any cause, whichever occurred first as assessed by the investigator.	From date of Randomization up to approx. 30 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS) (Key Secondary)	OS was defined as the time from randomization to date of death due to any cause. Patients entered the survival follow-up phase once they completed the safety follow up period (30 days after the last dose of midostaurin/placebo) in case of induction failure or if they had relapsed during post-treatment follow-up. Patients were then contacted by telephone every 3 months +/- 2 weeks or had a visit to follow up on their survival status, per Kaplan-Meier estimates.	Between randomization to date of death up to approx. 30 months
Percentage of Participants With Complete Remission (CR) and Complete Remission With Incomplete Hematological Recovery (CRi) But With Adequate Blood Count Recovery Rate.	Assessment was based on the International Working Group (IWG) criteria for AML as per investigator assessment. CR: Bone marrow: < 5% blasts no blasts with Auer rods; Peripheral blood: neutrophils ≥ 1.0 x 109/L platelets ≥ 100 x 109/L, no blasts; No evidence of extramedullary disease (such as central nervous system (CNS) or soft tissue involvement); Transfusion independent. CRi with adequate blood count recovery is defined as the following: Bone marrow < 5% blasts no blasts with Auer rods Peripheral blood Neutrophils >= 1.0 x 109/L and 50 x 109/L <=platelets < 100 x 109/L no blasts No evidence of extramedullary disease (such as CNS or soft tissue involvement).	At maximum 93 days from induction therapy start
Percentage of Participants With Minimal Residual Disease (MRD) Negative Status	MRD- rate was defined as the rate of participants reaching MRD at any timepoint. Participants with leukemic blasts below 0.1% were considered as MRD-negative based on leukemia-associated immunophenotype (LAIP). MRD was derived from bone marrow and blood data using cellular and molecular technologies and MRD status was measured using the flow cytometry assessments for LAIP irrespective of the investigator's overall clinical response assessment.	from start of treatment up to end of post-consolidation (approximately 17 months)
Percentage of Participants With Minimal Residual Disease (MRD) Negative Status During Post-consolidation Phase	MRD- rate was defined as the rate of participants reaching MRD at any timepoint during Post-consolidation phase. Participants with leukemic blasts below 0.1% were considered as MRD-negative based on leukemia-associated immunophenotype (LAIP). MRD was derived from bone marrow and blood data using cellular and molecular technologies and MRD status was measured using the flow cytometry assessments for LAIP irrespective of the investigator's overall clinical response assessment.	from start of post-consolidation to end of post-consolidation phase (up to 12 months)
Time to Measurable Residual Disease (MRD) Negativity by Flow Cytometry	Time to MRD- is defined as time from randomization to first occurrence of MRD-. Participants with leukemic blasts below 0.1% were considered as MRD-negative based on leukemia-associated immunophenotype (LAIP). MRD was derived from bone marrow and blood data using cellular and molecular technologies and MRD status was measured using the flow cytometry assessments for LAIP irrespective of the investigator's overall clinical response assessment.	From date of Randomization up to approx. 17 months
Disease-free Survival (DFS)	DFS as measured from the date of first CR or CRi with adequate blood count recovery to relapse or death due to any cause, whichever occurred first. Participants who did not relapse nor die were censored at the last adequate response assessment. Assessment was based on the IWG criteria for AML as per investigator assessment	From date of CR or CRi with adequate blood count recovery up to approx. 30 months
Cumulative Incidence of Relapse (CIR)	Cumulative Incidence of Relapse (CIR) was defined for participants with CR or CRi with adequate blood count recovery and was the time from achieving the CR or CRi with adequate blood count recovery until the onset of relapse from CR or CRi with adequate blood recovery. Participants without relapse were censored at the last adequate response assessment. Participants who died without relapse were counted as a competing cause of failure.	From date of CR or CRi with adequate blood count recovery up to approx. 30 months
Cumulative Incidence of Death (CID)	Cumulative Incidence of Death (CID) was defined for all participants achieving CR or CRi with adequate blood count recovery measured from the date of achievement of CR or CRi until the date of death due to any reason. Participants not known to have died were censored on the last contact date. Participants who experienced relapse were counted as a competing cause of failure.	From date of CR or CRi with adequate blood count recovery up to approx. 30 months
Time to CR or CRi With Adequate Blood Count Recovery	Time to CR or CRi with adequate blood count recovery was defined as the time from randomization to CR or CRi with adequate blood count recovery whichever occurred first	At maximum 93 days from induction therapy start
Time to Partial and Full Neutrophil Recovery	The time to neutrophil recovery was assessed for the following criteria: Partial neutrophil recovery: Number of days from start of treatment to the first day neutrophils ≥0.5 x 10^9/L. Full neutrophil recovery: Number of days from start of treatment to the first day neutrophils ≥1.0 x 10^9/L	At maximum 93 days from induction therapy start
Time to Partial and Full Platelet Recovery	Time to platelet recovery was assessed for the following criteria: Partial platelet recovery: Number of days from start of treatment to the first day platelets ≥50 x 10^9/L. Full platelet recovery: Number of days from start of treatment to the first day platelets ≥100 x 10^9/L.	At maximum 93 days from induction therapy start
Plasma Concentrations for Midostaurin and Its Metabolites: CGP52421 and CGP62221 for Non-poor Metabolizers	Serial pharmacokinetics (PK) samples were collected in Non-poor metabolizer participants to assess the plasma concentrations of midostaurin, CGP52421 and CGP62221.	from Induction (IND) phase 0hr (predose) to Post-consolidation phase (POSTCONS) 12hr
AUC0-t: Pharmacokinetic (PK) Parameter for Midostaurin and Its Metabolites: CGP52421 and CGP62221 at Cycle 1, Day 8	The AUC from time zero to a measurable concentration sampling time (t) (mass x time x volume-1). Note: as the last sampling time was at 12 h, AUC0-12h was determined after the first dose, reported at Cycle 1, Day 8	0 - 12 hrs
AUClast: Pharmacokinetic (PK) Parameter for Midostaurin and Its Metabolites: CGP52421 and CGP62221 at Cycle 1, Day 8	The AUC from time zero to the last measurable concentration sampling time after the first dose reported at Cycle 1, Day 8	0 - 12 hrs
Cmax: Pharmacokinetic (PK) Parameter for Midostaurin and Its Metabolites: CGP52421 and CGP62221 at Cycle 1, Day 8	The maximum (peak) observed plasma drug concentration after the first dose administration reported at Cycle 1, Day 8	0 - 12 hrs
Tmax: Pharmacokinetic (PK) Parameter for Midostaurin and Its Metabolites: CGP52421 and CGP62221 at Cycle 1, Day 8	The time to reach maximum (peak) plasma, blood, serum, or other body fluid drug concentration after single dose administration reported at Cycle 1, Day 8	0 - 12 hrs
Total Score for Each Time Point for the Functional Assessment of Cancer Therapy-Leukemia (FACT-Leu)	The total FACT-Leu score consists of 44 items with total scores ranging from 0 to 176. Higher scores indicate better health-related quality of life ( HRQoL). Negative changes from baseline indicate a worsening of HRQoL while positive changes indicate an improvement in HRQoL.	From date of Randomization up to approx. 18 months
Scores for Each Time Point for the EQ5D-5L (a Visual Analogue Scale (VAS))	The EQ5D-5L questionnaire assesses 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 response options (no problems, slight problems, moderate problems, severe problems and extreme problems) that reflect increasing levels of difficulty. The patient is asked to indicate his/her current health state by selecting the most appropriate level in each of the 5 dimensions. The questionnaire also included a Visual Analogue Scale (VAS), where the patient is asked to rate current health status on a scale of 0 to 100, with 0 being the worst imaginable health state.	From date of Randomization up to approx. 18 months

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals
• Investigators: Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Publications and helpful links

Helpful Links

• A Plain Language Trial Summary is available on novctrd.com

Study record dates

Study Major Dates

• Study Start (Actual): July 20, 2018
• Primary Completion (Actual): February 12, 2021
• Study Completion (Actual): February 12, 2021

Study Registration Dates

• First Submitted: March 26, 2018
• First Submitted That Met QC Criteria: April 18, 2018
• First Posted (Actual): April 30, 2018

Study Record Updates

• Last Update Posted (Actual): August 21, 2023
• Last Update Submitted That Met QC Criteria: August 16, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: idarubicin; AML; minimal residual disease; acute myeloid leukemia; cytarabine; combination treatment; PKC412; midostaurin; EFS; daunorubicin; Newly diagnosed FLT3-mutation negative; FLT3-MN (SR<0.05); induction failure; event free survival
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Midostaurin
• Other Study ID Numbers: CPKC412E2301; 2017-003540-21 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent expert panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data is currently available according to the process described on www.clinicalstudydatarequest.com.

Drug and device information, study documents

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