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Dasatinib in Polycythemia Vera

This study has been completed.
Sponsor:
Collaborator:
Bristol-Myers Squibb
Information provided by:
Weill Medical College of Cornell University
ClinicalTrials.gov Identifier:
NCT00538980
First received: October 2, 2007
Last updated: October 20, 2009
Last verified: October 2009
  Purpose

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.


Condition Intervention Phase
Polycythemia Vera
Drug: Dasatinib
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: The Use of Dasatinib (SPRYCEL) in Treating Patients With Polycythemia Vera (PV): A Phase II, Non-Randomized Study

Resource links provided by NLM:


Further study details as provided by Weill Medical College of Cornell University:

Primary Outcome Measures:
  • To evaluate the effect of dasatinib on the platelet count and the stabilization of hematocrit when restored by phlebotomy to normal range (HCT <45% for men, <42% for women). [ Time Frame: Lab tests will be performed weekly for the first month, then every 2 weeks for months 2 and 3 and monthly thereafter. ] [ Designated as safety issue: No ]
  • To determine change in performance status and development of side effects and complications in patients treated under this protocol. [ Time Frame: Patients will evaluated weekly for the first month, then every two weeks forr months 2 and 3, and monthly thereafter. ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • To determine changes in marrow cellularity, reticulin and fibrous content. [ Time Frame: Bone marrow analysis will be performed at baseline and month 6. ] [ Designated as safety issue: No ]
  • To determine change in cytogenetics if initially abnormal. [ Time Frame: Cytogenetics analysis will be performed at baseline and month 6. ] [ Designated as safety issue: No ]
  • To determine if quantitative change in JAK2 expression occurs as measured by quantitative pyrosequencing. [ Time Frame: JAK2 analysis will be performed at baseline and month 3. ] [ Designated as safety issue: No ]

Estimated Enrollment: 24
Study Start Date: April 2007
Primary Completion Date: October 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: All patients
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).
Drug: Dasatinib
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).

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00538980

Locations
United States, Georgia
Emory Winship Cancer Institute
Atlanta, Georgia, United States, 30322
United States, New York
Hematology/Oncology Associates of Rockland
New City, New York, United States, 10956
Weill Cornell Medical College - New York Presbyterian Hospital
New York, New York, United States, 10021
United States, Tennessee
The Jones Clinic
Germantown, Tennessee, United States, 38138
Sponsors and Collaborators
Weill Medical College of Cornell University
Bristol-Myers Squibb
Investigators
Principal Investigator: Richard T Slver, M.D. Weill Medical College of Cornell University
  More Information

No publications provided

Responsible Party: Richard Silver, M.D. / Professor of Medicine, Weill Medical College of Cornell University
ClinicalTrials.gov Identifier: NCT00538980     History of Changes
Other Study ID Numbers: CA180-104, 0701008940
Study First Received: October 2, 2007
Last Updated: October 20, 2009
Health Authority: United States: Institutional Review Board
United States: Food and Drug Administration

Keywords provided by Weill Medical College of Cornell University:
Polycythemia Vera
PV
P Vera

Additional relevant MeSH terms:
Polycythemia
Polycythemia Vera
Bone Marrow Diseases
Hematologic Diseases
Myeloproliferative Disorders
Dasatinib
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protein Kinase Inhibitors

ClinicalTrials.gov processed this record on November 24, 2014