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).

ClinicalTrials.gov Identifier: NCT03280030

Novartis Reference Number: CPKC412A2220

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All compounds are either investigational or being studied for (a) new use(s). Efficacy and safety have not been established. There is no guarantee that they will become commercially available for the use(s) under investigation. 

Study Description

This study will evaluate the efficacy and safety of 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).

Condition 
Acute Myeloid Leukemia
Phase 
Phase 2
Overall status 
Active, not recruiting
Enrollment count 
67 participants
Start date 
Oct 21, 2010
Completion date 
Nov 18, 2022
Gender 
All
Age(s)
18 Years - 70 Years (Adult, Older Adult)

Interventions

Drug
Midostaurin
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
Drug
Placebo
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.

Eligibility Criteria

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 Locations

Hong Kong
Novartis Investigative Site
-
Hong Kong,
-
Hong Kong
Japan
Novartis Investigative Site
-
Nagoya-city, 466-8650
Aichi
Japan
Novartis Investigative Site
-
Toyoake city, 470 1192
Aichi
Japan
Novartis Investigative Site
-
Kashiwa, 277 8577
Chiba
Japan
Novartis Investigative Site
-
Fukuoka city, 812-8582
Fukuoka
Japan
Novartis Investigative Site
-
Fukushima city, 960 1295
Fukushima
Japan
Novartis Investigative Site
-
Sapporo, 064 0804
Hokkaido
Japan
Novartis Investigative Site
-
Isehara, 259-1193
Kanagawa
Japan
Novartis Investigative Site
-
Kochi city, 781 8555
Kochi
Japan
Novartis Investigative Site
-
Sakyo Ku, 606 8507
Kyoto
Japan
Novartis Investigative Site
-
Nagasaki-city, 852-8501
Nagasaki
Japan
Novartis Investigative Site
-
Okayama city, 701-1192
Okayama
Japan
Novartis Investigative Site
-
Osaka Sayama, 589 8511
Osaka
Japan
Novartis Investigative Site
-
Osaka-city, 543-8555
Osaka
Japan
Novartis Investigative Site
-
Hamamatsu, 432-8580
Shizuoka
Japan
Novartis Investigative Site
-
Shimotsuke, 329-0498
Tochigi
Japan
Novartis Investigative Site
-
Bunkyo ku, 113-8677
Tokyo
Japan
Novartis Investigative Site
-
Bunkyo-ku, 113-8603
Tokyo
Japan
Novartis Investigative Site
-
Shinagawa ku, 141 8625
Tokyo
Japan
Novartis Investigative Site
-
Aomori, 030 8553
-
Japan
Novartis Investigative Site
-
Fukuoka, 810-8563
-
Japan
Novartis Investigative Site
-
Osaka, 534-0021
-
Japan
Novartis Investigative Site
-
Yamagata, 990 9585
-
Japan
Korea, Republic of
Novartis Investigative Site
-
Seoul, 06591
Seocho Gu
Korea, Republic of
Novartis Investigative Site
-
Seoul, 03722
-
Korea, Republic of
Novartis Investigative Site
-
Seoul, 06351
-
Korea, Republic of
Russian Federation
Novartis Investigative Site
-
Moscow, 123182
-
Russian Federation
Novartis Investigative Site
-
Moscow, 125284
-
Russian Federation
Novartis Investigative Site
-
St Petersburg, 194044
-
Russian Federation
Taiwan
Novartis Investigative Site
-
Putzu City, 61363
Chiayi Hsien
Taiwan
Novartis Investigative Site
-
Kaohsiung City, 83301
-
Taiwan
Novartis Investigative Site
-
Taipei, 10002
-
Taiwan
Novartis Investigative Site
-
Taoyuan, 33305
-
Taiwan
Vietnam
Novartis Investigative Site
-
Hanoi,
-
Vietnam

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