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.
- 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.
- 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
- 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
- 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