Selective Inhibitor of Nuclear Export (SINE) Selinexor (KPT-330) in Patients With Myelodysplastic Syndromes
Condition: Myelodysplastic Syndromes
MeSH terms: Preleukemia; Myelodysplastic Syndromes; Syndrome
Intervention: selinexor (KPT-330)
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 25.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Selinexor (KPT-330); Selective Inhibitor of Nuclear Export (SINE); 14-005

Summary:

      The purpose of this study is to see if selinexor will improve the blood counts and bone
      marrow function in people with your type of MDS.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Written informed consent in accordance with federal, local, and institutional
             guidelines

          -  Age ≥18 years

          -  Patients with Myelodysplastic Syndromes refractory (primary or acquired resistance) to
             hypomethylating agents(decitabine or 5-azacytidine). At least 4 1- month cycles of
             prior decitabine or SGI-110 OR 6 1-month cycles of 5-azacytidine (IV, subcutaneous, or
             oral is required unless the patient has progressive disease prior to completing the
             required number of cycles.

          -  Histologically confirmed diagnosis of a Myelodysplastic Syndrome, meeting criteria for
             any subtype in the FAB or WHO classification systems with any IPSS score.

          -  Patients with MDS who relapse after allogeneic stem cell transplant are eligible if
             they received standard dose decitabine or 5-azacytidine prior to or after stem cell
             transplant as defined in inclusion criteria 3.

          -  If patient has undergone prior allogeneic stem cell transplant, they must be greater
             than 100 days post transplant and have ≤ grade 2 graft-versus-host disease

          -  There is no upper limit on the number of prior treatments provided all
             inclusion/exclusion criteria are met.

          -  Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2

          -  Patients receiving erythropoietin (darbepoetin, epoetin alfa) must be on a stable dose
             and with stable transfusion requirement or hemoglobin level during the 8 weeks prior
             to study entry.

          -  Adequate hepatic function within 21 days prior to C1D1: total bilirubin <2 times the
             upper limit of normal (ULN), asparate aminotransferase (AST) <2.5 times ULN and
             alanine aminotransferase (ALT) <2.5 times ULN.

          -  Adequate renal function within 21 days prior to C1D1: estimated creatinine clearance
             of ≥ 30 mL/min, calculated using the formula of Cockcroft and Gault.

          -  Female patients of child-bearing potential must agree to use dual methods of
             contraception and have a negative serum pregnancy test at screening, and male patients
             must use an effective barrier method of contraception if sexually active with a female
             of child-bearing potential. Acceptable methods of contraception are condoms with
             contraceptive foam, oral, implantable or injectable contraceptives, contraceptive
             patch, intrauterine device, diaphragm with spermicidal gel, or a sexual partner who is
             surgically sterilized or post-menopausal. For both male and female patients, effective
             methods of contraception must be used throughout the study and for three months
             following the last dose.

        Exclusion Criteria:

          -  Patients who are pregnant or lactating;

          -  Chemotherapy or immunotherapy or any other anticancer therapy ≤3 weeks prior to cycle
             1 day 1. Hydroxyurea may be continued until 72 hours prior to first dose and at least
             24 hours before the baseline bone marrow aspiration is performed;

          -  Major surgery within four weeks before Day 1;

          -  Unstable cardiovascular function defined as symptomatic ischemia, uncontrolled
             clinically significant conduction abnormalities (ie: ventricular tachycardia on
             antiarrhythmics are excluded and 1st degree AV block or asymptomatic LAFB/RBBB will
             not be excluded), congestive heart failure (CHF) of NYHA Class ≥3, or myocardial
             infarction (MI) within 3 months;

          -  Uncontrolled active infection requiring systemic antibiotics, antivirals, or
             antifungals within one week prior to first dose; Prophylactic antimicrobials are
             permitted.

          -  Known to be HIV seropositive;

          -  Known active hepatitis A, B, or C infection; or known to be positive for HCV RNA or
             HBsAg (HBV surface antigen);

          -  Patients with another active malignancy. Asymptomatic sites of disease are not
             considered active. Treated or untreated sites of disease may be considered inactive if
             they are stable for at least 2 months and are not expected to require therapy for 4
             months.

          -  Patients with significantly diseased or obstructed gastrointestinal tract or
             uncontrolled vomiting or diarrhea.

          -  Grade ≥2 peripheral neuropathy at baseline (within 21 days prior to cycle 1 day 1).

          -  History of seizures, movement disorders or cerebrovascular accident within the past 1
             years prior to cycle 1 day 1.

          -  Patients with macular degeneration with markedly decreased visual acuity, patients
             with markedly decreased visual acuity (no specific etiology) or uncontrolled glaucoma.

          -  Patients who are significantly below their ideal body weight (BMI < 17)..

          -  Serious psychiatric or medical conditions that could interfere with treatment.