Efficacy & Safety Study of KPT-330 in Erythropoietin-Refractory Lower-Risk Myelodysplastic Syndrome Patients (SIER)

A Phase 2, Open-Label, Single Arm Study Evaluating the Efficacy and Safety of the Selective Inhibitor of Nuclear Export (SINE) Selinexor (KPT-330) in Patients With Erythropoietin (EPO)-Refractory Lower-Risk Myelodysplastic Syndrome (MDS)

This is an open-label study designed to evaluate the safety and efficacy of the selective inhibitor of nuclear export (SINE) compound, Selinexor given orally to patients with transfusion-dependent, EPO-refractory lower-risk MDS (Low risk and Intermediate-1 as defined by IPSS).

Study Overview

• Status: Withdrawn
• Conditions: Myelodysplastic Syndrome
• Intervention / Treatment: Drug: Selinexor

Detailed Description

This is a single-arm, open-label, study designed to evaluate the safety and efficacy of the selective inhibitor of nuclear export (SINE) compound, Selinexor given orally to patients with transfusion-dependent, EPO-refractory lower-risk MDS (Low risk and Intermediate-1 as defined by IPSS). Patients will be dosed at the clinic on clinic visit days and received Selinexor for dosing at home on additional days.

Patients will be evaluated for disease response according to the 2006 IWG response criteria for MDS. This includes evaluation for altering the natural history of disease, cytogenic response hematologic improvement, and quality of life.

• Study Type: Interventional
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Diagnosis of Low risk or Intermediate-1 risk MDS with any cytogenetic abnormalities (according to the IPSS criteria); patients must have bone marrow biopsy/aspiration or tumor tissue available from within 1 month prior to first dose or collected during the Screening period.
• Patients >18 years at Screening who are not candidates for hematopoietic cell transplantation.
• Received 1 prior line of treatment; typically erythroid-stimulating agents (ESAs).
• Red blood cell (RBC) transfusion-dependent anemia while treated with or after discontinuation of EPO. Transfusion dependence is defined as the requirement for at least 2 units of RBCs transfused during the 8 weeks prior to study initiation.

Exclusion Criteria:

• Use of recombinant EPO within 8 weeks prior to screening.
• Patient has a concurrent active malignancy or prior history of malignancy other than MDS (except basal cell or squamous cell carcinoma of the skin and in situ of the cervix) unless free of disease for at least 1 year.

• Unstable cardiovascular function:

  • Symptomatic ischemia,
  • Uncontrolled clinically significant conduction abnormalities (i.e., ventricular tachycardia on anti-arrhythmic agents are excluded; 1st degree atrioventricular (AV) block or asymptomatic Left anterior fascicular block/Right bundle branch block (LAFB/RBBB) will not be excluded), or
  • Congestive heart failure (CHF) New York Heart Association (NYHA) Class ≥3, or myocardial infarction (MI) within 3 months.
• Uncontrolled infection requiring parenteral antibiotics, antivirals, or antifungals within 1 week prior to first dose. Infections controlled on concurrent anti-microbial agents are acceptable, and anti-microbial prophylaxis per institutional guidelines is acceptable.
• Active bleeding Grade 3-4, in the last 4 weeks prior to enrollment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Selinexor; 60 mg once weekly	Drug: Selinexor; 60 mg on Day 1 of each week for a 4 week cycle, given for ≥6 cycles.; Other Names: KPT-330

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hematologic improvement (based on the 2006 International Working Group (IWG) response criteria)	Hematologic improvement in erythroid, platelet, and neutrophil counts, evaluated based on the 2006 International Working Group (IWG) response criteria for MDS.	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall response rate	Overall response is defined as complete remission (CR) or partial remission (PR).	6 months
Quality of Life (QOL-E) MDS Questionnaire)	Evaluate quality of life using the Quality of Life-E (QOL-E) MDS Questionnaire	6 months

Collaborators and Investigators

• Sponsor: Karyopharm Therapeutics Inc

Study record dates

Study Major Dates

• Study Start: November 1, 2015
• Primary Completion (Anticipated): December 1, 2017
• Study Completion (Anticipated): May 1, 2019

Study Registration Dates

• First Submitted: April 27, 2015
• First Submitted That Met QC Criteria: April 30, 2015
• First Posted (Estimate): May 1, 2015

Study Record Updates

• Last Update Posted (Estimate): January 26, 2023
• Last Update Submitted That Met QC Criteria: January 24, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Keywords: Refractory; Myelodysplastic Syndrome (MDS); Karyopharm; KPT-330; Selinexor; Erythropoietin (EPO); SIER
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Disease; Bone Marrow Diseases; Hematologic Diseases; Precancerous Conditions; Syndrome; Myelodysplastic Syndromes; Preleukemia
• Other Study ID Numbers: KCP-330-014