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Midostaurin

Protein Kinase Inhibitors

Enzyme Inhibitors

Patients must have an unequivocal diagnosis of de novo-CBFL, prior to start midostaurin, documented by rearrangement of Core Binding Factor (CBF) genes, namely AML1-ETO and CBFB-MYH11. The experimental arm involves the administration of Midostaurin orally 50 mg (two 25 mg tablets) twice a day, from the end of induction chemotherapy, for 14 days. Patients should take Midostaurin at approximately 12 hours intervals. During all consolidation cycles, Midostaurin 50 mg (two 25 mg tablets) is administered orally twice a day, on days 8-21. Patients in complete remission after 3 cycles of remission consolidation therapy, will receive Midostaurin continuation therapy for 12 months. Midostaurin 50 mg (two 25 mg tablets) will be given orally twice a day for 12 months.

Midostaurin associated with standard chemotherapy in patients with core-binding factor leukemia

Roberto Cairoli, MD

Eirika Ravelli, MD

Erika Ravelli, MD

The purpose of this single-arm, open label, phase-II trial, is to determine whether the association of Midostaurin to standard induction, consolidation therapy and in maintenance therapy as single agent, is effective in decrease relapse incidence, in patients with CBF-AML. The single-arm, open label, phase-II study is based on data obtained from previous clinical and pre-clinical studies, obtained by use of Midostaurin in patients with Acute Myeloid Leukemia (with or without FLT3 mutations) and in patients with Mast cell disorders (characterized by mutations in the C-KIT gene). The investigators believe that Midostaurin, associated with standard therapy Anthracycline/AraC Induction, to the consolidation regimen with high doses of araC and maintenance therapy to single agent in patients with acute myeloid leukemia core-binding factor can significantly reduce the incidence of recurrence of the disease, occurring in 40-50% of cases treated with standard therapy

In this prospective, Interventional, Single-Arm, Open-Label, Phase-II Trial aims at demonstrating a decrease in the 2-year Relapse Incidence (RI) and in the 2-year Cumulative Relapse Incidence among the Midostaurin-treated patients compared to a cohort of historical controls. The investigators established that a 20% net reduction in the 2-year RI may be a clinically significant goal. So the investigators set our RI objective at 28%. Furthermore, the investigators will assess if the experimental treatment may obtain an increased 5-years Overall, Disease-Free and Event free Survival. The safety profile of Midostaurin given in combination with induction and consolidation chemotherapy and as a single agent in maintenance in CBFL patients will also be assessed.

Core binding factor acute myeloid leukemia (CBF-AML) patients

Midostaurin Associated With Standard Chemotherapy in Patients With Core-binding Factor Leukemia

Prospective Evaluation of a Continuation Therapy With Midostaurin in Adult Patients With Core-binding Factor Leukemia and Integrated Genetic Analysis: a Multi-center Phase II Study

To show that the percentage of relapsed patients is 28% or below

To determine overall survival from achievement of first complete remission

Incidence of toxicity, defined as adverse events that are classified as either possibly, probably, or definitely related to study treatment per National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03. Frequency and severity of adverse events will be collected and summarized by descriptive statistics. The maximum grade for each type of toxicity will be recorded for each patient, and frequency tables will be reviewed to determine toxicity patterns. An adverse event is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.

To determine disease-free survival from achievement of first complete remission

To determine event-free survival from diagnosis

Spots Global Cancer Trial Database for minimal residual disease monitoring