A Study to Evaluate Safety and Efficacy of Selinexor in Combination With Ruxolitinib in Participants With Myelofibrosis

Inclusion Criteria:

Diagnosis of primary MF or post-essential thrombocythemic or post-polycythemia 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 ≥450 cubic centimeter (cm^3) by MRI or CT-scan.
Participants with dynamic international prognostic scoring system (DIPSS) risk category of intermediate-1, intermediate-2, or high-risk.
Participants ≥18 years of age.
Eastern Cooperative Oncology Group (ECOG) performance status of less than or equal to (≤) 2.
Platelet count ≥100 * 10^9/Liter (L).
Absolute neutrophil count (ANC) ≥1.5 * 10^9/L.
Serum direct bilirubin ≤1.5 * upper limit of normal (ULN); Aspartate transaminase (AST) and alanine transaminase (ALT) ≤2.5 * ULN.
Creatinine clearance (CrCl) greater than (>) 15 milliliters per minute (mL/min) based on the Cockcroft and Gault formula.
Participants with active hepatitis B virus (HBV) are eligible if antiviral therapy for hepatitis B has been given for >8 weeks and viral load is less than (<) 100 international units/milliliter (IU/mL).
Participants with untreated hepatitis C virus (HCV) are eligible there is documentation of negative viral load per institutional standard.
Participants with history of human immunodeficiency virus (HIV), are eligible if participants have cluster of differentiation 4 (CD4)+ T-cell counts ≥350 cells/microliter, negative viral load per institutional standard, and no history of acquired immunodeficiency syndrome (AIDS)-defining opportunistic infections in the last year.
Female participants of childbearing potential must have a negative serum pregnancy test at screening and agree to use highly effective methods of contraception throughout the study and for one month following the last dose of study treatment. Childbearing potential excludes: Age >50 years and naturally amenorrhoeic for >1 year, or previous bilateral salpingo-oophorectomy, or hysterectomy.
Male participants who are sexually active must use highly effective methods of contraception throughout the study and for one month following the last dose of study treatment. Must agree not to donate sperm during the study treatment period.
Participants must sign the written informed consent in accordance with federal, local and institutional guidelines.

Exclusion Criteria:

>5% blasts in peripheral blood or >10% blasts in bone marrow (accelerated phase).
Received previous treatment with Janus kinase (JAK) inhibitors for MF (treatment with hydroxyurea for up to 2 weeks is allowed).
Previous treatment with selinexor or other exportin-1 (XPO1) inhibitors.
Impairment of gastrointestinal (GI) function or GI disease that could significantly alter the absorption of selinexor.
Received strong cytochrome P450 3A (CYP3A) inhibitors ≤7 days prior to selinexor dosing or strong CYP3A inducers ≤14 days prior to selinexor dosing.
Major surgery <28 days prior to cycle 1 day 1 (C1D1).
Uncontrolled (i.e. clinically unstable) infection requiring parenteral antibiotics, antivirals, or antifungals within 7 days prior to first dose of study treatment; however, prophylactic use of these agents is acceptable (including parenteral).
Any life-threatening illness, medical condition, or organ system dysfunction which, in the Investigator's opinion, could compromise the patient's safety, prevent the patient from giving informed consent, or being compliant with the study procedures.
Female participants who are pregnant or lactating.