Clinical Trials /

Selinexor in Myelofibrosis Refractory or Intolerant to JAK1/2 Inhibitors

NCT03627403

Description:

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.

Related Conditions:
  • Myelofibrosis Transformation in Essential Thrombocythemia
  • Polycythemia Vera, Post-Polycythemic Myelofibrosis Phase
  • Primary Myelofibrosis
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: HCI114354
  • NCT ID: NCT03627403

Conditions

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

Interventions

DrugSynonymsArms
SelinexorSelinexor, all patients

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Selinexor, all patientsExperimentalSingle Arm Study, all patients will get selinexor
  • Selinexor

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 (≤ 7 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 Gilbert's syndrome who must
                  have a total bilirubin < 3 × ULN

               -  Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 2 × ULN.

          -  Renal (within 28 days prior to C1D1):

               -  Estimated creatinine clearance (CrCl) ≥ 20 mL/min using the Cockroft and Gault
                  formula [(140-Age) × Mass (kg)/(72 × creatinine mg/dL), multiply by 0.85 if the
                  patient is female] OR

               -  Measured CrCl ≥ 20 mL/min by 24-hour urine collection.

                    -  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 v5.04 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.

          -  BSA < 1.4 m2 at baseline, calculated by the Dubois or Mosteller methods.

          -  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 with circulating lymphocytes > 50,000/mm3 (50 G/L)

          -  Subjects who are breastfeeding and unwilling to stop while on study
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Change in spleen volume
Time Frame:Up to 6 months
Safety Issue:
Description: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. Change and percentage change in spleen volume from baseline to EOT as measured by MRI or CT (in applicable patients).

Secondary Outcome Measures

Measure:Adverse Events that Occur
Time Frame:Up to 6 months
Safety Issue:
Description: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).
Measure:Change in symptoms score
Time Frame:Up to 6 months
Safety Issue:
Description:Proportion of patients with ≥ 50% reduction of total symptoms score as measured by the MPN-Symptoms Assessment Form (MPN-SAF) from baseline to cycle 7 day 1. The score will be reported as one mean score of all of the questions in the questionnaire. The higher the score, the worse the symptom.
Measure:Overall response
Time Frame:Up to 6 months
Safety Issue:
Description:Overall response rate according to the 2013 IWG-MRT consensus criteria for treatment response in primary and secondary MF (post-PV and post-ET).
Measure:Overall Survival
Time Frame:Up to 24 months
Safety Issue:
Description:Overall survival from the initiation of study therapy to 24 months.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:University of Utah

Last Updated

January 24, 2020