Selinexor (KPT-330) Plus FLAG-Ida for the Treatment of Relapsing/Refractory AML
Condition: Acute Myeloid Leukemia
MeSH terms: Leukemia, Myeloid; Leukemia, Myeloid, Acute
Study type: Interventional
Phase: Phase 1

Summary: 
      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).
    

Detailed description: 
      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).
    

Intervention name(s): Selinexor; fludarabine; idarubicin; cytarabine; G-CSF
Intervention type(s): Drug; Drug; Drug; Drug; Drug
Intervention description(s): 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; 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
Intervention MeSH terms: Cytarabine; Fludarabine; Idarubicin
Intervention model: Sequential Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Acute Myeloid Leukemia; Relapsed; Refractory; Selinexor