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
