Dasatinib in Polycythemia Vera

A Phase II, Non-Randomized Study of the Use of Desatinib (Sprycel) in Treating Patients With Polycythemia Vera (PV) BMS Protocol Number: CA180-104

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.

Study Overview

• Status: Terminated
• Conditions: Polycythemia Vera
• Intervention / Treatment: Drug: Dasatinib

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory Winship Cancer Institute
  • New York
    • New City, New York, United States, 10956
      • Hematology/Oncology Associates of Rockland
    • New York, New York, United States, 10021
      • Weill Cornell Medical College - New York Presbyterian Hospital
  • Tennessee
    • Germantown, Tennessee, United States, 38138
      • The Jones Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

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).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Lab tests will be performed weekly for the first month, then every 2 weeks for months 2 and 3 and monthly thereafter.
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.	Patients will evaluated weekly for the first month, then every two weeks forr months 2 and 3, and monthly thereafter.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Bone marrow analysis will be performed at baseline and month 6.
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.	Cytogenetics analysis will be performed at baseline and month 6.
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.	JAK2 analysis will be performed at baseline and month 3.

Collaborators and Investigators

• Sponsor: Weill Medical College of Cornell University
• Collaborators: Bristol-Myers Squibb
• Investigators: Principal Investigator: Richard T Slver, M.D., Weill Medical College of Cornell University

Study record dates

Study Major Dates

• Study Start (Actual): April 30, 2007
• Primary Completion (Actual): August 25, 2010
• Study Completion (Actual): August 27, 2010

Study Registration Dates

• First Submitted: October 2, 2007
• First Submitted That Met QC Criteria: October 2, 2007
• First Posted (Estimate): October 3, 2007

Study Record Updates

• Last Update Posted (Actual): June 20, 2017
• Last Update Submitted That Met QC Criteria: May 23, 2017
• Last Verified: May 1, 2017

More Information

Terms related to this study

• Keywords: Polycythemia Vera; PV; P Vera
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Site; Bone Marrow Diseases; Hematologic Diseases; Myeloproliferative Disorders; Bone Marrow Neoplasms; Hematologic Neoplasms; Polycythemia Vera; Polycythemia; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Dasatinib
• Other Study ID Numbers: 0701008940; CA180-104