Study of Oral Dasatinib in Subjects With Myelodysplastic Syndrome (MDS) and Excess Marrow Blasts

Inclusion Criteria

• Documented diagnosis of MDS or Myeloproliferative Disorders (MPS/MPD) with blast percentage > 10% in bone marrow, MDS/AML with 10% in bone marrow
• Chronic myelomonocytic leukemia (CMML) with blast percentage > 10% in bone marrow
• Myelodysplastic / Myeloproliferative (MDS/MPD) syndromes with blast percentage > 10% in bone marrow
• Acute myeloid leukemia with Multilineage Dysplasia (MDS/AML) with 50,000 off hydroxyurea for >72 hours
• Malignancy [other than the one treated in this study] requiring radiotherapy or systemic treatment within past 3 years
• Chemotherapy or any agent with activity in MDS or AML concurrent with the study.
• Chemotherapy for MDS or AML prior to enrollment not allowed other than Azacitidine or Decitabine >2 months prior to first dose
• Concurrent medical condition which may increase the risk of toxicity, including:
• Pleural or pericardial effusion
• Serious medical condition, unstable medical co-morbidity, psychiatric illness that will prevent subject from signing informed consent form or place them at unacceptable risk if they participate
• Cardiac Symptoms, including:
• Uncontrolled angina, congestive heart failure or myocardial infarction (MI) within 6 months
• Diagnosed congenital long QT syndrome
• History of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or Torsades de Pointes)
• Prolonged QTc interval on pre-entry electrocardiogram (> 450 msec)
• Hypokalemia or hypomagnesemia if cannot be corrected
• History of significant bleeding disorder unrelated to cancer, including:
• Congenital bleeding disorders
• Acquired bleeding disorder within 1 year
• Ongoing or recent (≤ 3 months) significant gastrointestinal bleeding
• Concomitant Medications, consider the following prohibitions:
• Drugs generally accepted to have risk of causing Torsades de Pointes(Must discontinue drug 7 days prior to starting dasatinib)
• Concomitant use of H2 blockers or proton pump inhibitors with dasatinib not recommended. Use of antacids should be considered in place of H2 blockers or proton pump inhibitors in patients receiving dasatinib therapy.
• On-going requirement for treatment with platelet function inhibitor or anti-coagulation.
• Must discontinue St. Johns Wort while receiving dasatinib therapy
• Must agree that intravenous (IV) bisphosphonates be withheld for first 8 weeks of Dasatinib therapy due to risk of hypocalcemia.
• May not be receiving any prohibited CYP3A4 inhibitors
• Women:
• Positive pregnancy test at baseline
• Pregnant or breastfeeding
• Prisoners or patients who are compulsorily detained for treatment of either psychiatric or physical (e.g., infectious) illness