A Study of Midostaurin Efficacy and Safety in Newly Diagnosed Patients With FLT3-mutated AML

NCT03280030 | Completed Phase 2 Results DMC

• 1 other identifier: CPKC412A2220
• Study Type: interventional
• Target: 67
• Locations: 6 countries
• Sites: 34

Brief Summary

This study evaluated 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).

Conditions

Acute Myeloid Leukemia

Keywords

midostaurin; PKC412; cytarabine; daunorubicin; acute myeloid leukemia; combination treatment; FLT3; acute myeloid leukemia (AML); acute myelogenous leukemia (AML)

Outcome Measures

Primary Outcomes (2)

• Percentage of Safety Events (Part 1, Japan Only)

  Percentage 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 was determined by the Independent Safety Committee (ISC) to be definitely or probably related to midostaurin. Percentage was calculated based on the percentage of subjects with safety event out of 3 evaluable subjects in Part 1.

  up to Day 21 of the first Consolidation cycle; cycle = 28 days

• Event Free Survival (EFS) (Part 2 - Randomized, Controlled)

  Event Free survival is 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 complete remission (CR) within an induction 2, relapse after CR, or death due to any cause, whichever occurs first. The objective was to evaluate the efficacy based on EFS of midostaurin versus placebo in combination with daunorubicin/cytarabine induction, with high-dose cytarabine consolidation, and with midostaurin single agent continuation therapy in newly diagnosed patients with FLT3-mutated AML.

  up to 3 years after last patient started treatment

Secondary Outcomes (11)

• Overall Survival

  up to 3 years after last patient started treatment

• Percentage of Participants With Complete Remission (CR)

  up to 3 years after last patient started treatment

• Percentage of Participants With Cumulative Incidence of Relapse (CIR)

  up to 3 years after last patient started treatment

• Pharmakinetics (PK) for Midostaurin: AUClast & AUC0-t

  Induction Phase: Pre-dose and 1, 3, 6 and 12 hours post dose in Cycle 1 Day 8

• Pharmakinetics (PK) for Midostaurin: Cmax

  Induction Phase: Pre-dose and 1, 3, 6 and 12 hours post dose in Cycle 1 Day 8

Study Arms (2)

Midostaurin

EXPERIMENTAL

Patients took study drug on day 8-21 during induction and consolidation phase; then on days 1-28 for 12 cycles in the continuation (post consolidation) phase.

Drug: Midostaurin

Placebo

PLACEBO COMPARATOR

Patients took placebo on day 8-21 during induction and consolidation phase; then on days 1-28 for 12 cycles in the continuation (post consolidation) phase.

Drug: Placebo

Interventions

Midostaurin DRUG

Midostaurin 50 mg \[two 25 mg capsules\] were administered twice per day by mouth on day 8-21 during induction and consolidation phase; then on days 1-28 for 12 cycles in the continuation (post consolidation) phase.

Also known as: PKC412

Midostaurin

Placebo DRUG

Placebo, two capsules, were administered twice per day by mouth on day 8-21 during induction and consolidation phase; then on days 1-28 for 12 cycles in the continuation (post consolidation) phase.

Placebo

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (34)

Novartis Investigative Site

Pokfulam, Hong Kong

Location

Novartis Investigative Site

Nagoya, Aichi-ken, 466-8650, Japan

Location

Novartis Investigative Site

Toyoake, Aichi-ken, 470 1192, Japan

Location

Novartis Investigative Site

Kashiwa, Chiba, 277 8577, Japan

Location

Novartis Investigative Site

Fukuoka, Fukuoka, 812-8582, Japan

Location

Novartis Investigative Site

Fukushima, Fukushima, 960 1295, Japan

Location

Novartis Investigative Site

Sapporo, Hokkaido, 064 0804, Japan

Location

Novartis Investigative Site

Isehara, Kanagawa, 259-1193, Japan

Location

Novartis Investigative Site

Nagasaki, Nagasaki, 852-8501, Japan

Location

Novartis Investigative Site

Okayama, Okayama-ken, 701-1192, Japan

Location

Novartis Investigative Site

Osaka, Osaka, 543-8555, Japan

Location

Novartis Investigative Site

Ōsaka-sayama, Osaka, 589 8511, Japan

Location

Novartis Investigative Site

Hamamatsu, Shizuoka, 432-8580, Japan

Location

Novartis Investigative Site

Shimotsuke, Tochigi, 329-0498, Japan

Location

Novartis Investigative Site

Bunkyo Ku, Tokyo, 113-8677, Japan

Location

Novartis Investigative Site

Bunkyo-ku, Tokyo, 113-8603, Japan

Location

Novartis Investigative Site

Shinagawa Ku, Tokyo, 141 8625, Japan

Location

Novartis Investigative Site

Aomori, 030 8553, Japan

Location

Novartis Investigative Site

Fukuoka, 810-8563, Japan

Location

Novartis Investigative Site

Kochi, 781 8555, Japan

Location

Novartis Investigative Site

Kyoto, 606 8507, Japan

Location

Novartis Investigative Site

Osaka, 534-0021, Japan

Location

Novartis Investigative Site

Yamagata, 990 9585, Japan

Location

Novartis Investigative Site

Moscow, 123182, Russia

Location

Novartis Investigative Site

Moscow, 125284, Russia

Location

Novartis Investigative Site

Saint Petersburg, 197341, Russia

Location

Novartis Investigative Site

Seoul, Seocho Gu, 06591, South Korea

Location

Novartis Investigative Site

Seoul, 03722, South Korea

Location

Novartis Investigative Site

Seoul, 06351, South Korea

Location

Novartis Investigative Site

Putzu City, Chiayi Hsien, 61363, Taiwan

Location

Novartis Investigative Site

Kaohsiung City, 83301, Taiwan

Location

Novartis Investigative Site

Taipei, 10002, Taiwan

Location

Novartis Investigative Site

Taoyuan District, 33305, Taiwan

Location

Novartis Investigative Site

Hanoi, 100000, Vietnam

Location

Related Links

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

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

midostaurin

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

novartis.email@novartis.com

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 8, 2017
• First Posted: September 12, 2017
• Study Start: April 6, 2018
• Primary Completion: November 14, 2022
• Study Completion: November 14, 2022
• Last Updated: March 20, 2025
• Results First Posted: February 11, 2025

Record last verified: 2025-03

Locations

JP (22); RU (3); HK (1); VN (1); KR (3); TW (4)