Selinexor and Pacritinib in JAK Inhibitor-naïve MF Patients With Cytopenias

Exclusion Criteria

• •Prior treatment with Janus kinase (JAK) inhibitors
• •Prior treatment with selinexor or other Exportin 1 (XPO1) inhibitors
• •Treatment with any MF-directed therapy (including investigational therapies and excluding hydroxyurea) within 2 weeks or 5.5 half-lives, whichever is shorter, of Cycle 1 Day 1
• •Completed hematopoietic cell transplant (HCT)
• •Prior splenectomy, splenic irradiation, or splenic artery embolization within 6 months of Cycle 1 Day 1
• •Impairment of gastrointestinal (GI) function or GI disease that could significantly alter the absorption of pacritinib or selinexor, including any unresolved nausea, vomiting, or diarrhea \> National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v6.0 Grade 1
• •Uncontrolled or currently progressing ocular toxicities
• •Moderate or severe cardiovascular disease meeting one or both of the below criteria:
• •* Presence of cardiac disease, including a myocardial infarction within 6 months prior to study entry, unstable angina pectoris, New York Heart Association Class III/IV congestive heart failure, or uncontrolled hypertension
• •* Documented major electrocardiogram (ECG) abnormalities (not responding to medical treatments)
• •Grade 2 or greater bleeding event within the past 6 months
• •QT corrected by the Fridericia method (QTcF) prolongation \> 480 ms or other factors that increase the risk for QT interval prolongation (eg, hypokalemia \[defined as serum potassium \< 3.0 mEq/L that is persistent and refractory to correction\], or history of long QT interval syndrome)
• •Recipient of organ transplant
• •History of major surgery or any planned surgical procedures within 28 days prior to Cycle 1 Day 1
• •Other malignancy within the last three years, other than curatively treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, organ-confined or treated non-metastatic prostate cancer with normal prostate-specific antigen, in situ breast carcinoma after complete surgical resection, or superficial/non-invasive transitional cell bladder carcinoma.
• •Presence of active serious infection
• •Use of any prohibited medications (5.8) within two weeks or five half-lives, whichever is longer, prior to Cycle 1 Day 1
• •Women who are pregnant or lactating
• •Any serious, unstable medical or psychiatric condition that would prevent (as judged by the Investigator) the subject from signing the informed consent form (ICF) or any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if they were to participate in the study or confounds the ability to interpret data from the study
• •Is or has an immediate family member (e.g., spouse, parent/legal guardian, sibling, or child) who is investigational site or sponsor staff directly involved with this trial, unless prospective IRB approval (by chair or designee) is given allowing exception to this criterion for a specific subject