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

Study Overview
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Brief Summary
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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).

Detailed Description
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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.

Official Title
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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)

Conditions
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Myelodysplastic Syndrome

Intervention / Treatment
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* Drug: Selinexor


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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KPT-330, Karyopharm, Selinexor, SIER, Myelodysplastic Syndrome (MDS), Erythropoietin (EPO), Refractory