AN OPEN-LABEL, MULTICENTER, PHASE 3B STUDY TO ASSESS THE SAFETY AND EFFICACY
POSTER 47
OF MIDOSTAURIN IN PATIENTS AGED ≥18 YEARS WITH NEWLY DIAGNOSED FLT3-
MUTATED ACUTE MYELOID LEUKEMIA (AML) WHO ARE ELIGIBLE FOR 7+3 OR 5+2
CHEMOTHERAPY
Sejla S Hodzic,1 Pilar Hernández,2 Bourras-Rezki Bengoudifa,3 Ana Rita Ferreira,4 Geralyn Gilotti1
(1)Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, USA;
(2)ICON Clinical Research, Barcelona, Spain;
(3)Novartis Pharma AG, Basel, Switzerland
(4)Novartis Farma S.p.A., Origgio, Italy
Background: AML is the most common type of acute leukemia in adults with age-dependent
incidence increase, resulting in >50% of AML patients being >60 years old. FLT3-mutated AML,
presented in ≈30% of the patient population, is associated with poor prognosis. In the phase 3,
randomized, placebo-controlled RATIFY trial, midostaurin (a multikinase FLT3 inhibitor) plus
chemotherapy had significantly improved overall and event-free survival versus chemotherapy alone
in newly diagnosed FLT3-mutated AML, leading to the regulatory approval of this regimen in the
majority of countries worldwide. The chemotherapy regimen used in RATIFY was the historical
standard 7+3. Understanding the evolution of clinical practice, this trial allows the variation of the
7+3 regimen, substitution of daunorubicin with idarubicin, no upper age limit, and the 5+2
chemotherapy regimen (usually used in advanced age to prevent toxicity and/or increase
tolerability).
Objectives: The aim of this pan-European, multicenter trial is to investigate safety and efficacy of
midostaurin 50 mg BID in combination with variation chemotherapy regimens and as a single-agent
maintenance.
Methods: CPKC412A2408 (NCT03379727) is an open-label, single-arm, phase 3b trial enrolling adults
aged ≥18 years with newly diagnosed FLT3-mutated AML, fit for chemotherapy. Bone marrow
aspiration results must be available within 15 days and FLT3 mutation status prior to day 7 of the first
induction cycle (C1D1), respectively. Per investigator’s choice, enrolled patients can start 7+3
(cytarabine 100-200 mg/m2/day on Days 1-7 and daunorubicin 60-90 mg/m2/day or idarubicin 12
mg/m2/day on Days 1-3) or 5+2 (reduced doses of these agents) induction chemotherapy and cannot
switch regimens once started. Patients will receive midostaurin on Days 8-28 for 1-2 cycles of
induction; those who achieve complete remission (CR) or CR with incomplete hematologic recovery
(CRi) will proceed to consolidation with cytarabine (1-3 g/m2) plus midostaurin (Days 8-28) for ≤4
cycles. Patients who maintain CR/CRi after completing consolidation will receive continuous dosing
of midostaurin for ≤12 cycles of maintenance (Days 1-28). The primary endpoint is safety. The
secondary endpoint is the proportion of patients with CR/CRi in induction, consolidation, and
maintenance.
Results: The first patient enrolled in February 2018 in Norway. The trial is ongoing with expected
total enrollment of 300 patients.
Conclusion/Summary: This study assesses the safety and efficacy of midostaurin in combination with
7+3 and 5+2 chemotherapy in an extended patient population. We hypothesize similar benefits and
risks associated with midostaurin in the RATIFY study are replicated with alternative chemotherapy
regimens.
Clinical trial information: NCT03379727
SCIENTIFIC
PROGRAMME
RARE SUBSETS OF
ACUTE LEUKAEMIA
TRACKING LEUKAEMIC
STEM CELLS (LSCs)
ROUTINE DIAGNOSIS
GENE EXPRESSION
AND MUTATIONAL
PROFILING
DEBATE 1 – ALL
PATIENTS WITH
INTERMEDIATE-RISK
AML MUST BE
TRANSPLANTED
INTERACTIVE
CASES 1 – MUTATION-BASED
THERAPY
OFF-LABEL
ROUNDTABLE –
SHOULD WE REALLY
USE NEW TARGETED
INHIBITORS AS SINGLE
AGENTS ?
ADDITION OF A 3RD
AGENT TO FRONTLINE
7+3
ROUNDTABLE –
CURATIVE OPTIONS
FOR OLDER AML
INTERACTIVE CASES 2
DEBATE 2 - BEST
TREATMENT FOR
NPM1-MUTATED AML IN
THE NEXT FUTURE ?
ALLOGENEIC
HAEMATOPOIETIC
STEM CELL
TRANSPLANTATION
(HSCT)
IMMUNOTHERAPY FOR
ACUTE LEUKAEMIA
DEBATE 3 - T-ALL:
WHERE ARE WE GOING
NOW?
SELECTED ABSTRACTS
AND CLINICAL
CASES FOR AN ORAL
PRESENTATION
SELECTED ABSTRACTS
FOR A POSTER
PRESENTATION
DISCLOSURES