Back to results

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

Primary Purpose

Myelodysplastic Syndrome

Status

Withdrawn

Phase

Phase 2

Locations

Study Type

Interventional

Intervention

Selinexor

About this trial

This is an interventional treatment trial for Myelodysplastic Syndrome focused on measuring KPT-330, Karyopharm, Selinexor, SIER, Myelodysplastic Syndrome (MDS), Erythropoietin (EPO), Refractory

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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.

Sites / Locations

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Selinexor

Arm Description

60 mg once weekly

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Overall response rate

Overall response is defined as complete remission (CR) or partial remission (PR).

Quality of Life (QOL-E) MDS Questionnaire)

Evaluate quality of life using the Quality of Life-E (QOL-E) MDS Questionnaire

Full Information

NCT ID

NCT02431351

First Posted

April 27, 2015

Last Updated

January 24, 2023

Sponsor

Karyopharm Therapeutics Inc

1. Study Identification

Unique Protocol Identification Number

NCT02431351

Brief Title

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

Acronym

SIER

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 Type

Interventional

2. Study Status

Record Verification Date

January 2023

Overall Recruitment Status

Withdrawn

Why Stopped

Trial never opened.

Study Start Date

November 2015 (undefined)

Primary Completion Date

December 2017 (Anticipated)

Study Completion Date

May 2019 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Karyopharm Therapeutics Inc

4. Oversight

Data Monitoring Committee

5. 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).

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Myelodysplastic Syndrome

Keywords

KPT-330, Karyopharm, Selinexor, SIER, Myelodysplastic Syndrome (MDS), Erythropoietin (EPO), Refractory

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

0 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Selinexor

Arm Type

Experimental

Arm Description

60 mg once weekly

Intervention Type

Drug

Intervention Name(s)

Selinexor

Other Intervention Name(s)

KPT-330

Intervention Description

60 mg on Day 1 of each week for a 4 week cycle, given for ≥6 cycles.

Primary Outcome Measure Information:

Title

Hematologic improvement (based on the 2006 International Working Group (IWG) response criteria)

Description

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

Time Frame

6 months

Secondary Outcome Measure Information:

Title

Overall response rate

Description

Overall response is defined as complete remission (CR) or partial remission (PR).

Time Frame

6 months

Title

Quality of Life (QOL-E) MDS Questionnaire)

Description

Evaluate quality of life using the Quality of Life-E (QOL-E) MDS Questionnaire

Time Frame

6 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

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.

12. IPD Sharing Statement

Learn more about this trial

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

We'll reach out to this number within 24 hrs