Selinexor in Myelofibrosis Refractory or Intolerant to JAK1/2 Inhibitors

Inclusion Criteria: * Male or female subject aged ≥ 18 years. * Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 * Diagnosis of primary myelofibrosis (PMF), post-essential thrombocytosis (PET-MF) or post-polycythemia vera (PPV-MF). * Life expectancy ≥ 6 months. * Prior treatment with ruxolitinib or any experimental JAK1/2 inhibitor with any one or more of the following: a. Inadequate response after being on ≥ 3 months of treatment defined by: i. Palpable spleen ≥ 10 cm below the left subcostal margin on physical examination at the screening visit OR ii. Palpable spleen ≥ 5cm below the left subcostal margin on physical examination at the screening visit AND active symptoms of MF at the screening visit defined presence of 1 symptom score of ≥ 5 or two symptom scores each of ≥ 3 using the Screening Symptoms Form (Appendix 6) b. Intolerant to ruxolitinib and/or other JAK1/2 inhibitors due to any grade ≥ 3 non-hematologic AEs of or any grade ≥ 2 AEs requiring treatment discontinuation AND palpable spleen ≥ 5cm below the left subcostal margin on physical examination at the screening visit. * Adequate organ function as defined as: * Hematologic (≤ 28 days prior to C1D1): * Total white blood cell (WBC) count ≥ 1000/mm3 * Absolute neutrophil count (ANC) ≥ 500/mm3 * Hemoglobin ≥ 7 g/dL * Platelet count ≥ 30,000/mm3 For patients receiving transfusion and growth factor support, the following delays must be observed between the last administration and hematologic laboratory screening assessments: • For hematopoietic growth factor support (including erythropoietin, darbepoetin, granulocyte-colony stimulating factor \[G-CSF\], granulocyte macrophage-colony stimulating factor \[GM-CSF\], and platelet stimulators \[e.g., eltrombopag, romiplostim, or interleukin-11\]): at least 2 weeks. Growth factor support, RBC and/or platelet transfusions are allowed as clinically indicated per institutional guidelines during the study. * Hepatic (≤ 28 days prior to C1D1): * Total bilirubin \< 1.5 × ULN except in patients with indirect hyperbilirubinemia due to hemolysis or with Gilbert's syndrome where total bilirubin should be \< 5 × ULN * Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \< 2.5 × ULN. * Renal (within 28 days prior to C1D1): * Estimated creatinine clearance (CrCl) ≥ 20 mL/min using the Cockcroft and Gault formula \[(140-Age) × Mass (kg)/(72 × creatinine mg/dL), multiply by 0.85 if the patient is female\] OR * Female patients of childbearing potential must have a negative serum pregnancy test (≤ 3 days prior to C1D1). * Female patients of childbearing potential must agree to use 2 methods of contraception throughout the study and for 3 months following the last dose of study treatment (including 1 highly effective and 1 effective method of contraception as defined in section 7.4) * Male patients must use an effective barrier method of contraception if sexually active with a female of childbearing potential. * Recovery to baseline or ≤ Grade 1 CTCAE v5.0 from toxicities related to any prior treatments including ruxolitinib or other experimental agents unless AE(s) are clinically nonsignificant and/or stable on supportive therapy. * Able to provide informed consent and willing to sign an approved consent form that conforms to federal and institutional guidelines. Exclusion Criteria: * Prior exposure to a SINE compound, including selinexor. * Patients who are below their ideal body weight and would be unduly impacted by changes in their weight, in the opinion of the investigator, will be excluded * Uncontrolled active infection requiring parenteral antibiotics, antivirals, or antifungals ≤ 1 week prior to C1D1. Patients on prophylactic antibiotics or with a controlled infection ≤ 1 week prior to C1D1 are acceptable. * Radiation, chemotherapy, immunotherapy, or any other anticancer therapy (including investigational therapies) ≤ 2 weeks. * Ruxolitinib or other JAK1/2 inhibitors ≤ at least 3 days or 5 half-lives prior to C1D1. * Major surgery ≤ 4 weeks prior to C1D1. * Known active hepatitis A, B, or C infection; or known to be positive for hepatitis C virus ribonucleic acid (RNA) or hepatitis B virus surface antigen. * Any active gastrointestinal dysfunction interfering with the patient's ability to swallow tablets, or any active gastrointestinal dysfunction that could interfere with absorption of study treatment. * Any life-threatening illness, organ system dysfunction, or serious psychiatric, medical, or other conditions/situations which, in the investigator's opinion, could compromise a patient's ability to give informed consent, safety, or compliance with the protocol. * Contraindication to any of the required concomitant drugs or supportive treatments. * Subjects taking prohibited medications as described in Section 6.3. Following discontinuation of prohibited medications, a washout period is required prior to initiating study treatment (the duration of the washout must be as clinically indicated, e.g. at least five half-lives). * Subjects who are breastfeeding and unwilling to stop while on study