Clinical Trial Finder

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.

Arms

Experimental: Phase 1a: Cohort 1: Selinexor 40 mg and Ruxolitinib 15/20 mg

Participants with MF will receive a dose of 40 milligrams (mg) of selinexor oral tablets once weekly (QW) on Days 1, 8, 15, and 22 of each 28-day cycle and ruxolitinib oral tablets 15 or 20 mg twice a day (BID).

Experimental: Phase 1a: Cohort 2: Selinexor 60 mg and Ruxolitinib 15/20 mg

Participants with MF will receive a dose of 60 mg of selinexor oral tablets QW on Days 1, 8, 15, and 22 of each 28-day cycle and ruxolitinib oral tablets 15 or 20 mg BID.

Experimental: Phase 1a: Cohort -1: Selinexor 20 mg and Ruxolitinib 15/20 mg

Participants with MF will receive a dose of 20 mg of selinexor oral tablet twice weekly (BIW) of each 28-day cycle and ruxolitinib oral tablets 15 or 20 mg BID.

Experimental: Phase 1b: RP2D: Selinexor and Ruxolitinib 15/20 mg

Participants with MF will receive recommended safe dose (estimated in Phase 1a) of selinexor oral tablets on Days 1, 8, 15, and 22 of each 28-day cycle and ruxolitinib oral tablets 15 or 20 mg BID.

Experimental: Phase 2: Selinexor RP2D and Ruxolitinib 15/20 mg

Participants with MF will receive recommended safe dose (estimated in Phase 1b) of selinexor oral tablets QW on Days 1, 8, 15, and 22 of each 28-day cycle and ruxolitinib oral tablets 15 or 20 mg BID.

Active Comparator: Phase 2: Ruxolitinib 15/20 mg

Participants with MF will receive ruxolitinib oral tablets 15 or 20 mg BID.

Interventions

Drug: - Selinexor

Formulation: 20 mg Tablet; Dose: 20, 40 (2 tablets of 20 mg), 60 mg (3 tablets of 20 mg); Route of Administration: Oral

Drug: - Ruxolitinib

Formulation: 5, 10 mg Tablet; Dose: 15, 20 mg; Route of Administration: Oral