Study Design:~This protocol corresponds to a multicenter, open-label, non-randomized, phase I study designed to determine the safety of the combination of selinexor with chemotherapy in young patients with relapsed or refractory AML.~The clinical trial is divided into pre-treatment, treatment (induction and consolidation cycles) and follow-up periods and consists of a phase I design in which es-calating doses of selinexor will be given to 3 groups, each with 3-6 patients until achieving the maximum tolerated dose (MTD).~Each cycle (second induction, consolidation or maintenance) of treatment will compromise 3 weeks of selinexor treatment, and at least one week off treatment. The new cycle will not start if there is an ongoing grade 3 or higher non-hematologic toxicity or persistent grade 3 neutropenia in patients achieving CR.~Study design allows a maximum of 18 patients.~Induction cycle (up to 2 cycles):~Treatment will consist of fludarabine 30 mg/m2/day intravenously on days 1 to 4, idarubicin 10 mg/m2/day intravenously on days 1 to 3, cytarabine 2 g/m2/day intravenously on days 1 to 4, G-CSF 300 mcg/m2/day subcutaneously from days -1 to 5. This schedule will be combined with oral selinexor (KPT-330) for three weeks at days and dose according to escalation level:~Level -1: Selinexor 40 mg/day, once weekly~Level 1: Selinexor 60 mg/day, once weekly~Level 2: Selinexor 80 mg/day, once weekly~Level 3: Selinexor 100 mg/day, once weekly If a partial response is obtained after the first cycle of treatment, an identical induction therapy will be administered.~If a patient achieves a complete remission after 1 or 2 cycles of FLAG-IDA plus selinexor, allogeneic stem cell transplantation (Allo-SCT) will be attempted. If Allo-SCT is not possible, this patient will receive consolidation treatment as described below.~Consolidation cycle (up to 2 cycles):~Treatment will consist of cytarabine 1 g/m2/day intravenously (3 hours) on days 1 to 6. This schedule will be combined with oral selinexor (the same dosage that was administered to the patient in the induction cycle).~At most, patients will receive up to 4 cycles of combined chemotherapy.~Maintenance cycle:~For patients in CR, and when an Allo-SCT is not feasible, a maintenance treatment with selinexor could be started for up to 6 cycles.~Selinexor will be given at the same level as during induction therapy in cycles of four weeks (3 weeks on selinexor and 1 week off).
This protocol corresponds to a multicenter, open-label, non-randomized, phase I study designed to determine the safety of the combination of selinexor with chemotherapy in young patients with relapsed or refractory AML.~The clinical trial is divided into pre-treatment, treatment (induction and consolidation cycles) and follow-up periods and consists of a phase I design in which es-calating doses of selinexor will be given to 3 groups, each with 3-6 patients until achieving the maximum tolerated dose (MTD).