NCT03661515

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

An Investigator Sponsored Phase I Trial of Selinexor (KPT-330) Plus FLAG-Ida for the Treatment of Relapsing/Refractory AML

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 16 (actual)
• Sponsor: PETHEMA Foundation · Academic / Other
• Sex: All
• Age: 18 Years – 65 Years
• Healthy volunteers: Not accepted

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).

Conditions

• Acute Myeloid Leukemia

Interventions

Type	Name	Description
DRUG	Selinexor	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
DRUG	fludarabine	fludarabine 30 mg/m2/day intravenously on days 1 to 4
DRUG	idarubicin	idarubicin 10 mg/m2/day intravenously on days 1 to 3
DRUG	cytarabine	cytarabine 2 g/m2/day intravenously on days 1 to 4
DRUG	G-CSF	G-CSF 300 mcg/m2/day subcutaneously from days -1 to 5

Timeline

• Start date: 2018-07-17
• Primary completion: 2019-07-15
• Completion: 2019-10-15
• First posted: 2018-09-07
• Last updated: 2020-05-20

Locations

4 sites across 1 country: Spain