Dasatinib in Polycythemia Vera
Condition: Polycythemia Vera
MeSH terms: Polycythemia Vera; Polycythemia
Intervention: Dasatinib
Intervention description: Patients will receive a once-daily oral administration of dasatinib at a dose of 100 mg QD (two 50 mg tablets taken together each day) for the duration of the study with the modifications as indicated. If the platelet count remains above 600,000/microL or the spleen remains enlarged in the absence of leukopenia or other side effects, the dose of dasatinib may be escalated to 120 mg QD (two 50 mg tablets plus one 20 mg tablet taken together each day).
Intervention MeSH terms: Dasatinib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 10.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Polycythemia Vera; PV; P Vera

Summary:

      The purpose for conducting this research study is to determine the feasibility of using
      dasatinib as a treatment for polycythemia vera and to determine the optimum treatment
      regimen.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Patients must be >= 18 years old

          2. Performance Status (ECOG) 0-3

          3. Previous therapies limited to interferon-alpha, hydroxyurea, anagrelide, and imatinib

          4. Patients may have documented resistance or intolerance to interferon-alpha, imatinib,
             hydroxyurea, or anagrelide, but must have been demonstrated to be phlebotomy dependent
             requiring 6 or more phlebotomies per year to maintain the target HCT.

          5. Patients may have newly diagnosed PV.

          6. Patients may have had inadequate phlebotomy control on hydroxyurea or imatinib.

          7. Adequate Organ Function

               -  Total bilirubin < 2.0 times the institutional Upper Limit of Normal (ULN)

               -  Hepatic enzymes (AST, ALT ) ≤ 2.5 times the institutional ULN

               -  Serum Na, K+, Mg2+, Phosphate and Ca2+³ Lower Limit of Normal (LLN)

               -  Serum Creatinine < 1.5 time the institutional ULN

               -  Hemoglobin, Neutrophil count, Platelets, PT, PTT all Grade 0-1

          8. Ability to take oral medication: dasatinib tablets may be swallowed whole, or may be
             ingested as a solution. Dasatinib tablets can be dissolved in juice, and can then be
             administered through a nasogastric tube.

          9. Women of childbearing potential (WOCBP) must have:

               -  A negative serum or urine pregnancy test within 72 hours prior to the start of
                  study drug administration

         10. Persons of reproductive potential must agree to use an adequate method of
             contraception throughout treatment and for at least 4 weeks after study drug is
             stopped.

         11. Signed written informed consent including HIPAA according to institutional guidelines

        Exclusion Criteria:

          1. Patients receiving busulfan within six weeks of Study Day 1.

          2. Patients receiving treatment with interferon-alpha within 4 weeks of Study Day 1.

          3. Patients receiving treatment with imatinib within 14 days of Study, Day 1.

          4. Patients with Grade 3 or 4 cardiac problems as defined by the New York Heart
             Association Criteria.

          5. Patients with a history of non-compliance to medical regimens or who are considered
             potentially unreliable.

          6. A malignancy [other than the one treated in this study], which required radiotherapy
             or systemic treatment within the past 5 years.

          7. Concurrent medical condition which may increase the risk of toxicity, including:

               -  Pleural or pericardial effusion of any grade

               -  Clinically-significant coagulation or platelet function disorder (e.g. known von
                  Willebrand's disease)

          8. Cardiac Symptoms, consider the following:

               -  Uncontrolled angina, congestive heart failure or MI within (6 months)

               -  Diagnosed congenital long QT syndrome

               -  Any 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)

               -  Subjects with hypokalemia or hypomagnesemia if it cannot be corrected

          9. History of significant bleeding disorder unrelated to cancer, including:

               -  Diagnosed congenital bleeding disorders (e.g., von Willebrand's disease)

               -  Diagnosed acquired bleeding disorder within one year (e.g., acquired anti-factor
                  VIII antibodies)

               -  Ongoing or recent (≤ 3 months) significant gastrointestinal bleeding

         10. Concomitant Medications, consider the following prohibitions:

               -  Drugs that are generally expected to have a risk of causing Torsades de Pointes
                  including: (Patients must discontinue drug 7 days prior to starting dasatinib)

               -  The concomitant use of H2 blockers or proton pump inhibitors with dasatinib is
                  not recommended. The use of antacids should be considered in place of H2 blockers
                  or proton pump inhibitors in patients receiving dasatinib therapy.

               -  Patient agrees to discontinue St. Johns Wort while receiving dasatinib therapy

               -  Patient agrees that IV bisphosphonates will be withheld for the first 8 weeks of
                  dasatinib therapy due to risk of hypocalcemia.

               -  Patient may not be receiving any prohibited CYP3A4 inhibitors

         11. Women:

               -  Unwilling or unable to use an acceptable method to avoid pregnancy for the entire
                  study period and for at least 4 weeks after cessation of study drug, or

               -  Have a positive pregnancy test at baseline, or

               -  Are pregnant or breastfeeding