A Study of Selinexor Monotherapy in Subjects With JAK Inhibitor (JAKi)-naïve Myelofibrosis and Moderate Thrombocytopenia
Myelofibrosis, Moderate Thrombocytopenia
About this trial
This is an interventional treatment trial for Myelofibrosis focused on measuring Myelofibrosis, Selinexor, Total Symptom Score, Myelofibrosis Symptom Assessment Form, Spleen Volume Reduction, TSS50, SVR35, JAK2, KPT-330, Pacritinib, Ruxolitinib, Thrombocytopenia
Eligibility Criteria
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 x 10^9/L to 100 x 10^9/L without platelet transfusion within 7 days prior to the first dose of the study drug. Absolute neutrophil count (ANC) >=1.0 × 10^9/L without need for growth factors within 7 days prior to the first dose of the study drug. 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 eligible 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 pulmonary hypertension. 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, and the option to continue thereafter.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Experimental
Experimental
Experimental
Experimental
Selinexor 60 mg (Arm 1)
Selinexor 40 mg (Arm 2)
Selinexor 60 mg (Optional Extension Arm)
Selinexor 40 mg (Optional Extension Arm)
Participants will receive selinexor 60 milligrams (mg) oral tablets once weekly (QW) (Days 1, 8, 15, and 22 of each 28-day cycle) until PD, intolerable toxicity, or until they meet the criteria for discontinuation of study treatment, death, or withdrawal of consent, whichever comes first.
Participants will receive selinexor 40 mg oral tablets QW (Days 1, 8, 15, and 22 of each 28-day cycle) until PD, intolerable toxicity, or until they meet the criteria for discontinuation of study treatment, death, or withdrawal of consent, whichever comes first.
Participants will receive selinexor 60 milligrams (mg) oral tablets once weekly (QW) (Days 1, 8, 15, and 22 of each 28-day cycle) until PD, intolerable toxicity, or until they meet the criteria for discontinuation of study treatment, death, or withdrawal of consent, whichever comes first. This arm may be initiated following a review of efficacy and safety data from the selinexor 60 mg treatment arm (Arm 1).
Participants will receive selinexor 40 milligrams (mg) oral tablets once weekly (QW) (Days 1, 8, 15, and 22 of each 28-day cycle) until PD, intolerable toxicity, or until they meet the criteria for discontinuation of study treatment, death, or withdrawal of consent, whichever comes first. This arm may be initiated following a review of efficacy and safety data from the selinexor 40 mg treatment arm (Arm 2).