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

Sponsor

Karyopharm Therapeutics Inc (Industry)

Overall Status

Withdrawn

CT.gov ID

NCT02431351

Collaborator

(none)

Enrollment

Arm

Duration (Months)

Study Details

Study Description

Brief Summary

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).

Condition or Disease	Intervention/Treatment	Phase
Myelodysplastic Syndrome	Drug: Selinexor	Phase 2

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 Design

Study Type:

Interventional

Actual Enrollment :

0 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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)

Study Start Date :

Nov 1, 2015

Anticipated Primary Completion Date :

Dec 1, 2017

Anticipated Study Completion Date :

May 1, 2019

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Hematologic improvement (based on the 2006 International Working Group (IWG) response criteria) [6 months]
Hematologic improvement in erythroid, platelet, and neutrophil counts, evaluated based on the 2006 International Working Group (IWG) response criteria for MDS.

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.