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 sponsor and potential other locations can be found on ClinicalTrials.gov for NCT03512197.
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.
Lead OrganizationNovartis Pharmaceuticals Corporation
