Clinical trial NCT00538980: Dasatinib in Polycythemia Vera
Official title: A Phase II, Non-Randomized Study of the Use of Desatinib (Sprycel) in Treating Patients With Polycythemia Vera (PV) BMS Protocol Number: CA180-104
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Polycythemia Vera
Keywords: Polycythemia Vera
PV
P Vera
Lead sponsor: Weill Medical College of Cornell University
Sponsor class: OTHER
Collaborators: name: Bristol-Myers Squibb
First posted: 2007-10-03
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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

Primary outcomes:
measure: Effect of Dasatinib on the Platelet Count and the Stabilization of Hematocrit When Restored by Phlebotomy to Normal Range
timeFrame: Lab tests will be performed weekly for the first month, then every 2 weeks for months 2 and 3 and monthly thereafter.
measure: Change in Performance Status and Development of Side Effects and Complications
timeFrame: Patients will evaluated weekly for the first month, then every two weeks forr months 2 and 3, and monthly thereafter.
Secondary outcomes:
measure: Changes in Marrow Cellularity, Reticulin and Fibrous Content
timeFrame: Bone marrow analysis will be performed at baseline and month 6.
measure: Change in Cytogenetics
timeFrame: Cytogenetics analysis will be performed at baseline and month 6.
measure: Change in JAK2 Allele Burden
timeFrame: JAK2 analysis will be performed at baseline and month 3.
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: Emory Winship Cancer Institute
state: Georgia
city: New City
country: United States
facility: Hematology/Oncology Associates of Rockland
state: New York
city: New York
country: United States
facility: Weill Cornell Medical College - New York Presbyterian Hospital
state: New York
city: Germantown
country: United States
facility: The Jones Clinic
state: Tennessee
Study officials:
affiliation: Weill Medical College of Cornell University
name: Richard T Slver, M.D.
role: PRINCIPAL_INVESTIGATOR
References: