NCT02403310

A Study of Selinexor in Combination With Daunorubicin and Cytarabine for Untreated AML

A Phase 1 Investigator Sponsored Study of Selinexor in Combination With Daunorubicin and Cytarabine in Patients With Previously Untreated Poor-Risk Acute Myeloid Leukemia

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 21 (actual)
• Sponsor: H. Lee Moffitt Cancer Center and Research Institute · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The main purpose of this study is to determine the safety of combining selinexor with daunorubicin and cytarabine. The maximal tolerated dose (MTD) of selinexor with daunorubicin and cytarabine will also be established.

Detailed description

Induction Therapy - Dose escalation of selinexor with Daunorubicin and cytarabine at fixed doses. Consolidation Phase - Patients who are in complete remission (CR) or complete remission with incomplete count recovery (CRi) by day ≤70 and have recovered from any previous non- hematologic toxicity to baseline or grade ≤1 by day ≤70 following induction chemotherapy may go on to receive consolidation therapy for up to 2 cycles. The consolidation treatment phase will include up to two courses of therapy (28 day cycles) as follows: Daunorubicin 45mg/m\^2/day (days 1-2) Cytarabine 100mg/m\^2/day (continuous infusion on days 1-5) Selinexor same dose as induction (days 1,3,8,10) unless dose limiting toxicity (DLT) dictates a dose reduction. Selinexor will be given 2 hours prior to daunorubicin on day 1. A second cycle of consolidation therapy using the same doses as above will be administered, at the investigators discretion, between 28 and 42 days following initiation of the first consolidation treatment, after peripheral blood counts have recovered to CR, CRi levels, and after recovery from any non-hematologic toxicity to baseline or grade ≤1. Dose escalation of Selinexor will not occur during the consolidation phase. Maintenance Phase - Patients who remain in CR, CRi after up to 2 cycles of consolidation and are not eligible for allogeneic stem cell transplant will be eligible for the maintenance phase of treatment after recovery from any previous non-hematologic toxicity to baseline or grade ≤1. Maintenance therapy will consist of: Selinexor at the same dose as induction on days 1 and 8 of a 21 day cycle. They will continue for a maximum of 12 months. Expansion Phase - Once the MTD has been established, there will be an expansion phase to enroll an additional 13 subjects at the MTD to better characterize the safety profile and tolerability.

Conditions

• Leukemia
• Acute Myeloid Leukemia
• AML

Interventions

Type	Name	Description
DRUG	Selinexor	Induction: Oral selinexor on days 1, 3, 8, 10, 15 and 17. * Dose Level 2: 80 mg twice weekly. * Dose Level 1 (starting dose): 60 mg twice weekly. * Dose Level -1: 40 mg twice weekly. Consolidation: Selinexor same dose as induction (days 1,3,8,10) unless dose limiting toxicity (DLT) dictates a dose reduction. Maintenance: Selinexor at the same dose as induction on days 1 and 8 a 21 day cycle. They will continue for a maximum of 12 months.
DRUG	Daunorubicin	Induction: Daunorubicin 60 mg/m\^2/day (days 1-3). Consolidation: Daunorubicin 45 mg/m\^2/day (days 1-2).
DRUG	Cytarabine	Induction: Cytarabine 100 mg/m\^2/day (days 1-7). Consolidation: Cytarabine 100 mg/m\^2/day (continuous infusion on days 1-5).

Timeline

• Start date: 2015-06-18
• Primary completion: 2016-09-13
• Completion: 2021-02-01
• First posted: 2015-03-31
• Last updated: 2022-10-03

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study