Last updated on October 2018

Selinexor (KPT-330) Plus FLAG-Ida for the Treatment of Relapsing/Refractory AML


Brief description of study

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 Study 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).

Clinical Study Identifier: NCT03661515

Contact Investigators or Research Sites near you

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Susana Vives, Dr

Hospital Germans Tries i Pujol, Badalona
Badalona, Spain
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Pilar Martinez-Sanchez, Dr

Hospital Universitario 12 de Octubre,
Madrid, Spain
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Pau Montesinos, Dr

Hospital la Fe
Valencia, Spain
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Juan Bergua, Dr

Hospital San Pedro de Alc ntara,
Cáceres, Spain
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