A Study of Selinexor Monotherapy in Subjects With JAK Inhibitor-naïve Myelofibrosis and Moderate Thrombocytopenia

Myelofibrosis Clinical Trial

— SENTRY-2  

Official title:

A Phase 2 Study to Evaluate the Efficacy and Safety of Selinexor Monotherapy in Subjects With JAK Inhibitor-naïve Myelofibrosis and Moderate Thrombocytopenia

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05980806
• Other study ID #: XPORT-MF-044
• Status: Recruiting
• Phase: Phase 2
• Start date: April 22, 2024
• Est. completion date: October 2028

Study information

• Verified date: June 2024
• Source: Karyopharm Therapeutics Inc
• Contact: Karyopharm Medical Information
• Phone: (888) 209-9326
• Email: clinicaltrials[@]karyopharm.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The main purpose of this study with corresponding optional expansion is to evaluate the efficacy of selinexor in JAKi-naïve participants with myelofibrosis (MF) and moderate thrombocytopenia based on spleen volume reduction (SVR). Additional efficacy and safety parameters will also be assessed during the study.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 118
• Est. completion date: October 2028
• Est. primary completion date: April 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Key Inclusion Criteria:

• A diagnosis of MF or post-ET or post-PV MF according to the 2016 World Health Organization (WHO) classification of MPN, confirmed by the most recent local pathology report.

• Measurable splenomegaly during the screening period as demonstrated by spleen volume of greater than equal to (>=) 450 cubic square centimeter (cm^3) by MRI or CT scan (results from MRI or CT imaging performed within 28 days prior to screening are acceptable).

• Participants with DIPSS risk category of intermediate-1 with symptoms, or intermediate-2, or high-risk.

• ECOG Performance Status less than or equal to (<=) 2.

• Platelet count of 50 to less than (<) 100 x 10^9/L without platelet transfusion within 7 days prior to the first dose of selinexor.

• Absolute neutrophil count (ANC) >=1.0 × 10^9/L without need for growth factors within 7 days prior to the first dose of selinexor.

• Adequate liver function as defined by the following: aspartate transaminase (AST) and alanine aminotransferase (ALT) <= 2.5 × upper limit normal (ULN) and serum total bilirubin <= 3×ULN.

• Calculated creatinine clearance (CrCl) greater than (>) 15 milliliter per minute (mL/min) based on the Cockcroft and Gault formula.

• Active symptoms of MF as determined by presence of at least 2 symptoms with a score >= 3 or total score of >= 10 at screening using the MFSAF V4.0.

• Participants must provide bone marrow biopsy samples (samples obtained up to 3 months prior to C1D1 are permitted) at screening and during the study.

• Participants currently not a candidate for stem cell transplantation.

• Participants must be willing to complete the MFSAF V4.0 daily during the study for evaluating the symptom response (i.e., TSS50).

Key Exclusion Criteria:

• More than 10% blasts in peripheral blood or bone marrow (accelerated or blast phase).

• Previous treatment with JAK inhibitors for MF.

• Previous treatment with selinexor or other XPO1 inhibitors.

• Female participants who are pregnant or lactating.

• Prior splenectomy, or splenic radiation within 6 months prior to C1D1.

• History of myocardial infarction, unstable angina, percutaneous transluminal coronary angioplasty (PTCA) or coronary artery bypass graft (CABG), cerebrovascular accident (stroke or transient ischemic attack [TIA]), ventricular arrhythmias, congestive heart failure New York Heart Association (NYHA) class > 2 within 6 months of C1D1.

• Participants unable to tolerate two forms of antiemetics prior to each dose for the first two cycles.

Related Conditions & MeSH terms

• Myelofibrosis
• Primary Myelofibrosis
• Thrombocytopenia

Intervention

Drug:
• Selinexor 60 mg
Participants will receive selinexor 60 mg oral tablets QW.
• Selinexor 40 mg
Participants will receive selinexor 40 mg oral tablets QW.
• Ruxolitinib
Participants will receive ruxolitinib 5 mg or 10 mg twice daily.
• Pacritinib
Participants will receive pacritinib 200 mg twice daily.
• Momelotinib
Participants will receive momelotinib 200 mg once daily.

Locations

Country	Name	City	State
United States	Cleveland Clinic	Cleveland	Ohio
United States	Maryland Oncology Hematology - Independent of SCRI/ US Oncology	Columbia	Maryland
United States	City of Hope - Duarte Main Site	Duarte	California

Sponsors (1)

Lead Sponsor	Collaborator
Karyopharm Therapeutics Inc

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of Participants with Spleen Volume Reduction 35 (SVR35) at Week 24.	Measured by Magnetic Resonance Imaging (MRI) or Computed Tomography (CT) Scan	At Week 24
Secondary	Number of Participants with Treatment-emergent Adverse Events (TEAEs), Severity of TEAEs, Treatment Related Adverse Events (TRAEs) and Serious Adverse Events (SAEs)		From start of drug administration up to 30 days after the last dose of study treatment (approximately 48 months)
Secondary	Proportion of Participants with Total Symptom Score 50 (TSS50) at Week 24.	Measured by the Myelofibrosis Symptom Assessment Form (MFSAF) V4.0. A higher Total Symptom Score (TSS) indicates a higher disease burden and thus a worse outcome.	At Week 24
Secondary	Proportion of Participants with Anemia Response at Week 24 as per the International Working Group Myeloproliferative Neoplasms Research and Treatment and European Leukemia Network (IWG-MRT and ELN) Criteria		At Week 24
Secondary	Overall Survival (OS)		From date of randomization to the date of death due to any cause or EoS (assessed at approximately 48 months)
Secondary	Overall Response Rate (ORR) as per IWG MRT and ELN Criteria		From Cycle 1 Day 1 (28-day cycle) up to EoS (approximately 48 months)
Secondary	Proportion of Participants with SVR35 at Any Time Point.	Measured by MRI or CT Scan.	From Baseline to EoS (approximately 48 months)
Secondary	Proportion of Participants with TSS50 at Any Time.	Measured by the MFSAF V4.0. A higher Total Symptom Score (TSS) indicates a higher disease burden and thus a worse outcome.	From Baseline to EoS (approximately 48 months)
Secondary	SVR35 Response in Pre-specified MF Participant Subgroups (Including by Gender, Age, and Geographic Region)		From Baseline up to EoS (approximately 48 months)
Secondary	TSS50 Response in Pre-specified MF Participant Subgroups (Including by Gender, Age, and Geographic Region)		From Baseline up to EoS (approximately 48 months)
Secondary	Anemia Response in Pre-specified MF Participant Subgroups (Including by Gender, Age, and Geographic Region)		From Baseline up to EoS (approximately 48 months)
Secondary	SVR35 Response in Participants who Receive as add-on Treatments (Ruxolitinib or Pacritinib or Momelotinib) to Selinexor and Single-agent Selinexor Only		At Week 24
Secondary	TSS50 Response in Participants who Receive as add-on Treatments (Ruxolitinib or Pacritinib or Momelotinib) to Selinexor and Single-agent Selinexor Only		At Week 24
Secondary	Anemia Response in Participants who Receive as add-on Treatments (Ruxolitinib or Pacritinib or Momelotinib) to Selinexor and Single-agent Selinexor Only		At Week 24
Secondary	Number of Participants with TEAEs, Severity of TEAEs, TRAEs and SAEs in Participants who Receive as add-on Treatments (Ruxolitinib or Pacritinib or Momelotinib) to Selinexor and Single-agent Selinexor Only		From start of drug administration up to 30 days after the last dose of study treatment (approximately 48 months)
Secondary	Area Under the Concentration-time Curve (AUC) of Selinexor		Pre-dose, 0.5, 1, 2, 4, 6, and 24 hours post-dose on Cycle 1 Day 15 and 2 hours post-dose on Cycle 2 Day 15 (28-day cycle)
Secondary	Maximum Plasma Concentration (Cmax) of Selinexor		Pre-dose, 0.5, 1, 2, 4, 6, and 24 hours post-dose on Cycle 1 Day 15 and 2 hours post-dose on Cycle 2 Day 15 (28-day cycle)
Secondary	Time at Which Cmax is Achieved (Tmax) of Selinexor		Pre-dose, 0.5, 1, 2, 4, 6, and 24 hours post-dose on Cycle 1 Day 15 and 2 hours post-dose on Cycle 2 Day 15 (28-day cycle)
Secondary	Duration of Receptor Occupancy or Exportin 1 (XPO1) mRNA Induction		From Baseline up to EoS (approximately 48 months)
Secondary	Proportion of Participants with Post-treatment Changes in Bone Marrow		From Baseline up to EoS (approximately 48 months)