Selinexor in Treating Patients with Myelofibrosis Intolerant or Resistant 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: * Inadequate response after being on >= 3 months of treatment defined by: ** Palpable spleen >= 10 cm below the left subcostal margin on physical examination at the screening visit OR ** Palpable spleen >= 5 cm 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 * Intolerant to ruxolitinib and/or other JAK1/2 inhibitors due to any grade >= 3 non-hematologic adverse events (AEs) of or any grade >= 2 AEs requiring treatment discontinuation AND palpable spleen >= 5 cm below the left subcostal margin on physical examination at the screening visit.
• Total white blood cell (WBC) count >= 1000/mm^3 (=< 28 days prior to cycle 1 day 1 [C1D1]).
• Absolute neutrophil count (ANC) >= 500/mm^3 (=< 28 days prior to C1D1).
• Hemoglobin >= 7 g/dL (=< 28 days prior to C1D1).
• Platelet count >= 30,000/mm^3 (=< 28 days prior to C1D1).
• 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, red blood cells (RBC) and/or platelet transfusions are allowed as clinically indicated per institutional guidelines during the study.
• Total bilirubin < 1.5 x upper limit of normal (ULN) except in patients with indirect hyperbilirubinemia due to hemolysis or Gilbert’s syndrome where total bilirubin should be < 5 ULN (=< 28 days prior to C1D1).
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 2.5 x ULN (=< 28 days prior to C1D1).
• Estimated creatinine clearance (CrCl) >= 20 mL/min using the Cockcroft and Gault formula (=< 28 days prior to C1D1).
• 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).
• 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 Common Terminology for Adverse Events (CTCAE) version (v) 5.0 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 selective inhibitor of nuclear export (SINE) compound, including selinexor.
• Body surface area (BSA) < 1.4 m^2 at baseline, calculated by the Dubois or Mosteller methods.
• 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. 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.