- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03280030
A Study of Midostaurin Efficacy and Safety in Newly Diagnosed Patients With FLT3-mutated AML
A Phase II, Randomized, Double-blind, Multi-center, Placebo-controlled Study to Evaluate the Efficacy and Safety of Twice Daily Oral Midostaurin in Combination With Daunorubicin/Cytarabine Induction, High-dose Cytarabine Consolidation, and Midostaurin Single Agent Continuation Therapy in Newly Diagnosed Patients With FLT3-mutated Acute Myeloid Leukemia (AML).
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
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Hong Kong, Hong Kong
- Novartis Investigative Site
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Aomori, Japan, 030 8553
- Novartis Investigative Site
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Fukuoka, Japan, 810-8563
- Novartis Investigative Site
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Kyoto, Japan, 606 8507
- Novartis Investigative Site
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Osaka, Japan, 534-0021
- Novartis Investigative Site
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Yamagata, Japan, 990 9585
- Novartis Investigative Site
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Aichi
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Nagoya-city, Aichi, Japan, 466-8650
- Novartis Investigative Site
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Toyoake city, Aichi, Japan, 470 1192
- Novartis Investigative Site
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Chiba
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Kashiwa, Chiba, Japan, 277 8577
- Novartis Investigative Site
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Fukuoka
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Fukuoka city, Fukuoka, Japan, 812-8582
- Novartis Investigative Site
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Fukushima
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Fukushima city, Fukushima, Japan, 960 1295
- Novartis Investigative Site
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Hokkaido
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Sapporo, Hokkaido, Japan, 064 0804
- Novartis Investigative Site
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Kanagawa
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Isehara, Kanagawa, Japan, 259-1193
- Novartis Investigative Site
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Kochi
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Kochi city, Kochi, Japan, 781 8555
- Novartis Investigative Site
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Nagasaki
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Nagasaki-city, Nagasaki, Japan, 852-8501
- Novartis Investigative Site
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Okayama
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Okayama city, Okayama, Japan, 701-1192
- Novartis Investigative Site
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Osaka
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Osaka Sayama, Osaka, Japan, 589 8511
- Novartis Investigative Site
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Osaka-city, Osaka, Japan, 543-8555
- Novartis Investigative Site
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Shizuoka
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Hamamatsu, Shizuoka, Japan, 432-8580
- Novartis Investigative Site
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Tochigi
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Shimotsuke, Tochigi, Japan, 329-0498
- Novartis Investigative Site
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Tokyo
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Bunkyo ku, Tokyo, Japan, 113-8677
- Novartis Investigative Site
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Bunkyo-ku, Tokyo, Japan, 113-8603
- Novartis Investigative Site
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Shinagawa ku, Tokyo, Japan, 141 8625
- Novartis Investigative Site
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Seoul, Korea, Republic of, 06351
- Novartis Investigative Site
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Seoul, Korea, Republic of, 03722
- Novartis Investigative Site
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Seocho Gu
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Seoul, Seocho Gu, Korea, Republic of, 06591
- Novartis Investigative Site
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Kirov, Russian Federation, 610027
- Novartis Investigative Site
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Moscow, Russian Federation, 125284
- Novartis Investigative Site
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Moscow, Russian Federation, 123182
- Novartis Investigative Site
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Samara, Russian Federation, 443079
- Novartis Investigative Site
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St Petersburg, Russian Federation, 194044
- Novartis Investigative Site
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Kaohsiung City, Taiwan, 83301
- Novartis Investigative Site
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Taipei, Taiwan, 10002
- Novartis Investigative Site
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Taoyuan, Taiwan, 33305
- Novartis Investigative Site
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Chiayi Hsien
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Putzu City, Chiayi Hsien, Taiwan, 61363
- Novartis Investigative Site
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Bangkok, Thailand, 10700
- Novartis Investigative Site
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Hanoi, Vietnam, 100000
- Novartis Investigative Site
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Diagnosis of AML (≥ 20% blasts in the bone marrow based on WHO 2016 classification). Patients with APL (acute promyelocytic leukemia) with PML-RARA are not eligible
- Documented presence of an ITD and/or TKD activating mutation in the FLT3 gene, as determined by analysis in a Novartis designated laboratory An exception will be patients who are enrolled into the part 1 in Japan, who may be treated with midostaurin irrespective of AML FLT3 genotype.
Patients must meet the following laboratory value criteria that indicate adequate organ function at the screening visit:
- Estimated creatinine clearance ≥ 30 ml/min
- Total bilirubin ≤ 1.5 x ULN, except in the setting of isolated Gilbert syndrome
- Aspartate transaminase (AST) ≤ 3.0 x ULN
- Alanine transaminase (ALT) ≤ 3.0 x ULN
- Suitability for intensive chemotherapy in the judgment of the investigator
Exclusion Criteria:
- Neurologic symptoms suggestive of CNS leukemia unless CNS leukemia has been excluded by a lumbar puncture. Patients with CSF fluid positive for AML blasts are not eligible
- Developed therapy-related AML after prior radiotherapy (RT) or chemotherapy for another cancer or disorder
- Known hypersensitivity to midostaurin, cytarabine or daunorubicin or to any of the excipients of midostaurin/placebo, cytarabine or daunorubicin
- Abnormal chest X-ray unless the abnormality represents a non-active, or non-clinically significant finding, such as scarring (subjects with controlled non active lung infection are eligible)
- Known impairment of gastrointestinal (GI) function or GI disease that might alter significantly the absorption of midostaurin
- Cardiac or cardiac repolarization abnormality
- Pregnant or nursing (lactating) women
- Women of child-bearing potential, unless they are using highly effective methods of contraception during dosing and for 4 months after stopping medication Other protocol-defined Inclusion/Exclusion criteria may apply.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Single Group Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: Midostaurin
Patients will take study drug on day 8-21 during induction and consolidation phase; then continuously during continuation phase.
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Midostaurin 50 mg [two 25 mg capsules] will be administered twice per day by mouth on day 8-21 during induction and consolidation phase; then continuously during continuation phase
Other Names:
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Placebo Comparator: Placebo
Patients will take placebo on day 8-21 during induction and consolidation phase; then continuously during continuation phase.
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Placebo two capsules will be administered twice per day by mouth on day 8-21 during induction and consolidation phase ; then continuously during continuation phase.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Incidence of Safety Events (Part 1, Japan only)
Time Frame: Day 21 of the first Consolidation cycle
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Incidence and severity of Safety Events, defined as death or serious adverse event leading to treatment discontinuation that occurs on or before Day 21 of the first Consolidation cycle.
This is is determined by the Independent Safety Committee to be definitely or probably related to midostaurin.
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Day 21 of the first Consolidation cycle
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Event Free Survival (Part 2 - randomized, controlled)
Time Frame: up to 3 years after last patient started treatment
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Event Free survival defined as the time from the date of randomization until an EFS event is observed.
An EFS event is defined as a failure to obtain a CR within an induction 2, relapse after CR, or death due to any cause, whichever occurs first.
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up to 3 years after last patient started treatment
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Overall Survival
Time Frame: up to 3 years after last patient started treatment
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Overall survival defined as the time from the date of randomization to date of death due to any cause
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up to 3 years after last patient started treatment
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Complete Remission
Time Frame: up to 3 years after last patient started treatment
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Complete Remission defined as the proportion of patients with a CR according to Chelson Criteria, at various timepoints
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up to 3 years after last patient started treatment
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Cumulative incidence of relapse (CIR)
Time Frame: up to 3 years after last patient started treatment
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CIR (only for patients who have achieved CR after study treatment initiation), is measured from the date of first CR to relapse or death due to AML, whichever occurs first.
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up to 3 years after last patient started treatment
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Metabolite CGP52421
Time Frame: Induction 1 Cycle 1 Day 8, Day 11, Day 15, Day 18 and Day 21, Consolidation Cycle 1 Day 8, Day 21, Cycle 3 Day 8, Day 21 Prior to first cycle of continuation cycle 1, Continuation Cycle 5, Continuation Cycle 9 and Completion Cycle 12
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Evaluate the pharmacokinetic of major metabolite of midostaurin CGP52421
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Induction 1 Cycle 1 Day 8, Day 11, Day 15, Day 18 and Day 21, Consolidation Cycle 1 Day 8, Day 21, Cycle 3 Day 8, Day 21 Prior to first cycle of continuation cycle 1, Continuation Cycle 5, Continuation Cycle 9 and Completion Cycle 12
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Metabolite CGP62221
Time Frame: Induction 1 Cycle 1 Day 8, Day 11, Day 15, Day 18 and Day 21, Consolidation Cycle 1 Day 8, Day 21, Cycle 3 Day 8, Day 21 Prior to first cycle of continuation cycle 1, Continuation Cycle 5, Continuation Cycle 9 and Completion Cycle 12
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Evaluate the pharmacokinetic of major metabolite of Midostaurin CGP62221.
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Induction 1 Cycle 1 Day 8, Day 11, Day 15, Day 18 and Day 21, Consolidation Cycle 1 Day 8, Day 21, Cycle 3 Day 8, Day 21 Prior to first cycle of continuation cycle 1, Continuation Cycle 5, Continuation Cycle 9 and Completion Cycle 12
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Quality of life (QoL) per European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30
Time Frame: Screening, D21 of each cycle of Induction and Consolidation; D1 of each cycle of Continuation, at end of treatment and during the post treatment follow up every 4 months during the first year
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EORTC)QLQ-C30 total score and functional scales scores as determined by the score and absolute change from baseline at each scheduled assessment.
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Screening, D21 of each cycle of Induction and Consolidation; D1 of each cycle of Continuation, at end of treatment and during the post treatment follow up every 4 months during the first year
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Quality of life (QoL) per Patient Global Impression of Change (PGIC)
Time Frame: D21 of each cycle of Induction and Consolidation; D1 of each cycle of Continuation, at end of treatment and during the post treatment follow up every 4 months during the first year
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PGIC score determined frequencies and percentages by scheduled timepoint.
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D21 of each cycle of Induction and Consolidation; D1 of each cycle of Continuation, at end of treatment and during the post treatment follow up every 4 months during the first year
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Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- CPKC412A2220
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
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 review 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 availability is according to the criteria and process described on www.clinicalstudydatarequest.com
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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