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

University of Utah1 site in 1 country17 target enrollmentMay 10, 2019

ConditionsPrimary Myelofibrosis Post-essential Thrombocythemia Myelofibrosis Post-polycythemia Vera Myelofibrosis

InterventionsSelinexor

DrugsSelinexor

Overview

Phase: Phase 2
Intervention: Selinexor
Conditions: Primary Myelofibrosis
Sponsor: University of Utah
Enrollment: 17
Locations: 1
Primary Endpoint: Count of Participants With Reduction in Spleen Volume
Status: Terminated
Last Updated: 10 months ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

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.

Registry

clinicaltrials.gov

Start Date

May 10, 2019

End Date

March 5, 2025

Last Updated

10 months ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

University of Utah

Responsible Party

Sponsor

Eligibility Criteria

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

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 C1D
•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 C1D
•Major surgery ≤ 4 weeks prior to C1D
•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.

Arms & Interventions

Selinexor, all patients

Single Arm Study, all patients will get selinexor

Intervention: Selinexor

Outcomes

Primary Outcomes

Count of Participants With Reduction in Spleen Volume

Time Frame: Up to 5.5 months

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.