Selinexor in Myelofibrosis Refractory or Intolerant to JAK1/2 Inhibitors (ESSENTIAL)

A Phase II Study to Evaluate the Efficacy and Safety of Selinexor in Patients With Myelofibrosis Refractory or Intolerant to JAK1/2 Inhibitors

This is a phase II, open label, prospective, single-arm study evaluating the efficacy and safety of selinexor in patients with PMF or secondary MF (PPV-MF or PET-MF) who are refractory or intolerant to ruxolitinib and/or any other experimental JAK1/2 inhibitors.

Study Overview

• Status: Terminated
• Conditions: Primary Myelofibrosis; Post-polycythemia Vera Myelofibrosis; Post-essential Thrombocythemia Myelofibrosis
• Intervention / Treatment: Drug: Selinexor

• Study Type: Interventional
• Enrollment (Actual): 17
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • Huntsman Cancer Institute/University of Utah

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Selinexor, all patients; Single Arm Study, all patients will get selinexor

Drug: Selinexor; Selinexor will be administered orally at a dose of 80 mg once weekly until IWG-MR disease progression, intolerable toxicity, or no clinical benefit per treating physician's discretion whichever occurs first. For patients enrolled after Protocol v7, Selinexor will be administered by oral route beginning at 40mg once weekly. Prior to protocol version 7, the starting dose of sSelinexor was 60 mg and 80 mg once weekly.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Count of Participants With Reduction in Spleen Volume	To assess the efficacy of selinexor on spleen volume reduction in subjects with myelofibrosis (PMF, PET-MF, or PPV-MF) refractory or intolerant to ruxolitinib and/or any other experimental JAK1/2 inhibitors. This outcome will report the number of subjects with ≥ 35% reduction in spleen volume as measured by MRI or CT abdomen from baseline to after six cycles of treatment or end of treatment. Patients who did not complete six cycles of treatment received an MRI at discontinuation of therapy. Patients who died prior to completing six cycles of treatment or a follow-up scan were considered non-responders.	Up to 5.5 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival	Overall survival at 24 months from the initiation of study therapy.	Up to 24 months
Adverse Events That Occur	To assess the safety/tolerability and further characterize the safety profile of selinexor in PMF, PET-MF, or PPV-MF patients refractory or intolerant to ruxolitinib and/or any other experimental JAK1/2 inhibitors. Secondary Endpoints: rate of adverse events (AEs) and serious adverse events (SAEs).	Up to 24 months
Percent Change of Spleen Volume	To further assess the efficacy and clinical activity of selinexor (by means of overall response) in subjects with myelofibrosis (PMF, PET-MF, or PPV-MF) refractory or intolerant to ruxolitinib and/or any other experimental JAK1/2 inhibitors. This outcome will report the mean percent change of spleen volume as measured by MRI or CT abdomen from baseline to after six cycles of treatment or end of treatment. Patients who did not complete six cycles of treatment received an MRI at discontinuation of therapy. Patients who died prior to completing six cycles of treatment or a follow-up scan were not included in this endpoint. The mean and standard will be reported for the change in spleen volume.	Up to 5.5 months
Change in Symptoms Score	To further assess the efficacy and clinical activity of selinexor (by means of reduction in symptoms) in subjects with myelofibrosis (PMF, PET-MF, or PPV-MF) refractory or intolerant to ruxolitinib and/or any other experimental JAK1/2 inhibitors. This outcome reports the count of patients with ≥ 50% reduction of total symptoms scores as measured by the Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF) from baseline after 6 cycles of treatment. Patients who did not complete 6 cycles of treatment will receive the MPN-SAF assessment at discontinuation of therapy. The MPN-SAF is a symptom assessment completed by the patients including fatigue, concentration, early satiety, inactivity, night sweats, itching, bone pain, abdominal discomfort, weight loss, and fevers. Scoring is from 0 (absent/as good as it can be) to 10 (worst imaginable/as bad as it can be) for each item. The MPN-SAF TSS is the sum of all the individual scores (0-100 scale).	Up to 5.5 months
Overall Response	To further assess the efficacy and clinical activity of selinexor (by means of overall response) in subjects with myelofibrosis (PMF, PET-MF, or PPV-MF) refractory or intolerant to ruxolitinib and/or any other experimental JAK1/2 inhibitors. Overall response according to the 2013 International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) consensus criteria for treatment response in primary and secondary MF (post-PV and post-ET). The IWG-MRT response categories are CR (Complete Response), PR (Partial Response), CI (Clinical Improvement), Anemia Response, Spleen Response, Symptoms Response, Progressive Disease, Stable Disease, Relapse.	Up to 24 months

Collaborators and Investigators

• Sponsor: University of Utah
• Collaborators: Karyopharm Therapeutics Inc
• Investigators: Principal Investigator: Srinivas Tantravahi, MD, University of Utah

Study record dates

Study Major Dates

• Study Start (Actual): May 10, 2019
• Primary Completion (Actual): August 16, 2023
• Study Completion (Actual): March 5, 2025

Study Registration Dates

• First Submitted: August 7, 2018
• First Submitted That Met QC Criteria: August 8, 2018
• First Posted (Actual): August 13, 2018

Study Record Updates

• Last Update Posted (Actual): June 19, 2025
• Last Update Submitted That Met QC Criteria: June 11, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Hematologic Diseases; Blood Coagulation Disorders; Bone Marrow Diseases; Hemorrhagic Disorders; Blood Platelet Disorders; Myeloproliferative Disorders; Bone Marrow Neoplasms; Hematologic Neoplasms; Thrombocytosis; Thrombocythemia, Essential; Polycythemia Vera; Polycythemia; Primary Myelofibrosis
• Other Study ID Numbers: HCI114354

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No