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Dasatinib in Polycythemia Vera

Primary Purpose

Polycythemia Vera

Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Dasatinib
Sponsored by
Weill Medical College of Cornell University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Polycythemia Vera focused on measuring Polycythemia Vera, PV, P Vera

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Emory Winship Cancer Institute
  • Hematology/Oncology Associates of Rockland
  • Weill Cornell Medical College - New York Presbyterian Hospital
  • The Jones Clinic

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

All patients

Arm 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).

Outcomes

Primary Outcome Measures

Effect of Dasatinib on the Platelet Count and the Stabilization of Hematocrit When Restored by Phlebotomy to Normal Range
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). Analysis was not completed because the study was terminated early due to lack of efficacy.
Change in Performance Status and Development of Side Effects and Complications
To determine change in performance status and development of side effects and complications in patients treated under this protocol. Analysis was not completed because the study was terminated early due to lack of efficacy.

Secondary Outcome Measures

Changes in Marrow Cellularity, Reticulin and Fibrous Content
To determine changes in marrow cellularity, reticulin and fibrous content. Analysis was not completed because the study was terminated early due to lack of efficacy.
Change in Cytogenetics
To determine change in cytogenetics if initially abnormal. Analysis was not completed because the study was terminated early due to lack of efficacy.
Change in JAK2 Allele Burden
To determine if quantitative change in JAK2 expression occurs as measured by quantitative pyrosequencing. Analysis was not completed because the study was terminated early due to lack of efficacy.

Full Information

First Posted
October 2, 2007
Last Updated
May 23, 2017
Sponsor
Weill Medical College of Cornell University
Collaborators
Bristol-Myers Squibb
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1. Study Identification

Unique Protocol Identification Number
NCT00538980
Brief Title
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

2. Study Status

Record Verification Date
May 2017
Overall Recruitment Status
Terminated
Why Stopped
This study was terminated due to lack of efficacy.
Study Start Date
April 30, 2007 (Actual)
Primary Completion Date
August 25, 2010 (Actual)
Study Completion Date
August 27, 2010 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Weill Medical College of Cornell University
Collaborators
Bristol-Myers Squibb

4. Oversight

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Polycythemia Vera
Keywords
Polycythemia Vera, PV, P Vera

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
10 (Actual)

8. Arms, Groups, and Interventions

Arm Title
All patients
Arm Type
Experimental
Arm 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 Type
Drug
Intervention Name(s)
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).
Primary Outcome Measure Information:
Title
Effect of Dasatinib on the Platelet Count and the Stabilization of Hematocrit When Restored by Phlebotomy to Normal Range
Description
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). Analysis was not completed because the study was terminated early due to lack of efficacy.
Time Frame
Lab tests will be performed weekly for the first month, then every 2 weeks for months 2 and 3 and monthly thereafter.
Title
Change in Performance Status and Development of Side Effects and Complications
Description
To determine change in performance status and development of side effects and complications in patients treated under this protocol. Analysis was not completed because the study was terminated early due to lack of efficacy.
Time Frame
Patients will evaluated weekly for the first month, then every two weeks forr months 2 and 3, and monthly thereafter.
Secondary Outcome Measure Information:
Title
Changes in Marrow Cellularity, Reticulin and Fibrous Content
Description
To determine changes in marrow cellularity, reticulin and fibrous content. Analysis was not completed because the study was terminated early due to lack of efficacy.
Time Frame
Bone marrow analysis will be performed at baseline and month 6.
Title
Change in Cytogenetics
Description
To determine change in cytogenetics if initially abnormal. Analysis was not completed because the study was terminated early due to lack of efficacy.
Time Frame
Cytogenetics analysis will be performed at baseline and month 6.
Title
Change in JAK2 Allele Burden
Description
To determine if quantitative change in JAK2 expression occurs as measured by quantitative pyrosequencing. Analysis was not completed because the study was terminated early due to lack of efficacy.
Time Frame
JAK2 analysis will be performed at baseline and month 3.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients must be >= 18 years old Performance Status (ECOG) 0-3 Previous therapies limited to interferon-alpha, hydroxyurea, anagrelide, and imatinib 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. Patients may have newly diagnosed PV. Patients may have had inadequate phlebotomy control on hydroxyurea or imatinib. 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 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. 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 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. Signed written informed consent including HIPAA according to institutional guidelines Exclusion Criteria: Patients receiving busulfan within six weeks of Study Day 1. Patients receiving treatment with interferon-alpha within 4 weeks of Study Day 1. Patients receiving treatment with imatinib within 14 days of Study, Day 1. Patients with Grade 3 or 4 cardiac problems as defined by the New York Heart Association Criteria. Patients with a history of non-compliance to medical regimens or who are considered potentially unreliable. A malignancy [other than the one treated in this study], which required radiotherapy or systemic treatment within the past 5 years. 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) 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 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 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 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Richard T Slver, M.D.
Organizational Affiliation
Weill Medical College of Cornell University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Emory Winship Cancer Institute
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Facility Name
Hematology/Oncology Associates of Rockland
City
New City
State/Province
New York
ZIP/Postal Code
10956
Country
United States
Facility Name
Weill Cornell Medical College - New York Presbyterian Hospital
City
New York
State/Province
New York
ZIP/Postal Code
10021
Country
United States
Facility Name
The Jones Clinic
City
Germantown
State/Province
Tennessee
ZIP/Postal Code
38138
Country
United States

12. IPD Sharing Statement

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Dasatinib in Polycythemia Vera

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