A Global Study of the Efficacy and Safety of Midostaurin + Chemotherapy in Newly Diagnosed Patients With FLT3 Mutation Negative (FLT3-MN) Acute Myeloid Leukemia (AML)
Condition: Acute Myeloid Leukemia (AML)
MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute
Intervention: Midostaurin; Placebo; Chemotherapy
Intervention description: Midostaurin was provided as 25 mg capsules 8PC, was supplied as double-blind in blister packs and taken orally.; Placebo was provided as 25 mg soft gelatin capsules 8PC, was supplied as double-blind in blister packs and taken orally.; Along with the study drug/placebo, chemotherapy was given as well: either Daunorubicin or Idarubicin and Cytarabine - all taken by i.v.
Intervention MeSH terms: Midostaurin
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 511.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Newly diagnosed FLT3-mutation negative; PKC412; midostaurin; cytarabine; daunorubicin; idarubicin; acute myeloid leukemia; AML; FLT3-MN (SR<0.05); combination treatment; induction failure; event free survival; EFS; minimal residual disease

Summary:

      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.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Diagnosis of AML (≥20% blasts in the bone marrow based on WHO 2016 classification).
             Patients with APL with PML-RARA are not eligible.

          2. Suitability for intensive induction chemotherapy in the judgment of the investigator

          3. Documented absence of an ITD and TKD activating mutation at codons D835 and I836 in
             the FLT3 gene, as determined by analysis in a Novartis designated laboratory using a
             validated clinical trial assay with clinical cutoff of 0.05 mutant to wild type signal
             ratio

          4. Age ≥18 years

          5. Laboratory values that indicate adequate organ function assessed locally at the
             screening visit

        Exclusion Criteria:

          1. Central nervous system (CNS) leukemia

          2. Therapy-related secondary AML

          3. Isolated extramedullary leukemia

          4. Prior therapy for leukemia or myelodysplasia

          5. AML after antecedent myelodysplasia (MDS) with prior cytotoxic treatment (e.g.,
             azacytidine or decitabine)

          6. Prior treatment with a FLT3 inhibitor (e.g., midostaurin, quizartinib, sorafenib)