Selinexor in Myelofibrosis Refractory or Intolerant to JAK1/2 Inhibitors

NCT03627403 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: HCI114354
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

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.

Conditions

Primary Myelofibrosis; Post-essential Thrombocythemia Myelofibrosis; Post-polycythemia Vera Myelofibrosis

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• Adverse Events That Occur

  Up to 24 months

• Percent Change of Spleen Volume

  Up to 5.5 months

• Change in Symptoms Score

  Up to 5.5 months

• Overall Response

  Up to 24 months

• Overall Survival

  Up to 24 months

Study Arms (1)

Selinexor, all patients

EXPERIMENTAL

Single Arm Study, all patients will get selinexor

Drug: Selinexor

Interventions

Selinexor DRUG

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.

Selinexor, all patients

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Utah: lead
• Karyopharm Therapeutics Inc: collaborator

Study Sites (1)

Huntsman Cancer Institute/University of Utah

Salt Lake City, Utah, 84112, United States

Location

MeSH Terms

Conditions

Primary Myelofibrosis

Interventions

selinexor

Condition Hierarchy (Ancestors)

Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases

Results Point of Contact

• Title: IIT Data Management Team
• Organization: Research Compliance Office, Huntsman Cancer Institute

IITDataManagement@hci.utah.edu

801-213-6215

Study Officials

• Srinivas Tantravahi, MD

  University of Utah

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Open label, non-randomized, prospective, single-arm study

Study Record Dates

• First Submitted: August 7, 2018
• First Posted: August 13, 2018
• Study Start: May 10, 2019
• Primary Completion: August 16, 2023
• Study Completion: March 5, 2025
• Last Updated: June 19, 2025
• Results First Posted: October 9, 2024

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)