SX-682 Treatment in Subjects With Myelodysplastic Syndrome Who Had Disease Progression or Are Intolerant to Prior Therapy

Inclusion Criteria:

• Diagnosis of MDS by World Health Organization criteria, and either

  1. International Prognostic Scoring System (IPSS) low risk or intermediate-1 risk without 5q deletion and failed treatment (no response, loss of response, progressive disease/treatment intolerance) following:

     i. 4 cycles hypomethylating agent; or ii. 4 cycles hypomethylating agent, or lenalidomide or erythropoietin stimulating agent (ESA).

  2. IPSS low risk or intermediate-1 risk with 5q deletion and failed treatment following:

     i. 4 cycles of lenalidomide and hypomethylating agent; or ii. 4 cycles of lenalidomide.

  3. IPSS intermediate-2 risk or high risk and failed treatment following 4 cycles hypomethylating agent.
• Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 2

• Screening laboratory values:

  1. Renal glomerular filtration rate (GFR) ≥ 30 ml/min;
  2. Aspartate aminotransferase (AST) / Alanine aminotransferase (ALT) ≤ 3.0 times upper limit of normal;
  3. Bilirubin < 1.5 times upper limit of normal;
  4. No history of HIV being HIV positive;
  5. No active Hepatitis B or Hepatitis C infection.
• Life expectancy ≥ 12 weeks.
• Women of childbearing potential (WOCBP) must use study specified contraception.
• WOCBP demonstrate negative pregnancy test.
• Not breastfeeding.
• Men sexually active must use study specified contraception.

Exclusion Criteria:

• Use of chemotherapeutic agents or experimental agents for MDS within 14 days of the first day of study drug treatment.
• Use of erythroid stimulating agents, Granulocyte-colony stimulating factor (G-CSF), or Granulocyte-macrophage colony-stimulating factor (GM-CSF) within 14 days of the first day of study drug treatment, or during the study.
• Mean triplicate heart rate-corrected QT interval (QTc) > 500 msec.

• Any of the following cardiac abnormalities:

  1. QT interval > 480 msec corrected using Fridericia's formula;
  2. Risk factors for Torsade de Pointes;
  3. Use of medication that prolongs the QT interval;
  4. Myocardial infarction ≤ 6 months prior to first day of study drug treatment;
  5. Unstable angina pectoris or serious uncontrolled cardiac arrhythmia.
• Any serious or uncontrolled medical disorder.
• Prior malignancy within the previous 3 years except for local cancers that have been cured.
• Subjects with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids, and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
• Use of other investigational drugs within 30 days of study drug administration.
• Major surgery within 4 weeks of study drug administration.
• Live-virus vaccination within 30 days of study drug administration.
• Allergy to study drug component.