Dasatinib in Polycythemia Vera

Polycythemia Vera Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00538980
• Other study ID #: 0701008940
• Secondary ID: CA180-104
• Status: Completed
• Phase: Phase 2
• First received: October 2, 2007
• Last updated: March 2, 2017
• Start date: April 30, 2007
• Est. completion date: August 27, 2010

Study information

• Verified date: March 2017
• Source: Weill Medical College of Cornell University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 10
• Est. completion date: August 27, 2010
• Est. primary completion date: August 25, 2010
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Polycythemia
• Polycythemia Vera

Intervention

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).

Locations

Country	Name	City	State
United States	Emory Winship Cancer Institute	Atlanta	Georgia
United States	The Jones Clinic	Germantown	Tennessee
United States	Hematology/Oncology Associates of Rockland	New City	New York
United States	Weill Cornell Medical College - New York Presbyterian Hospital	New York	New York

Sponsors (2)

Lead Sponsor	Collaborator
Weill Medical College of Cornell University	Bristol-Myers Squibb

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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).		Lab tests will be performed weekly for the first month, then every 2 weeks for months 2 and 3 and monthly thereafter.
Primary	To determine change in performance status and development of side effects and complications in patients treated under this protocol.		Patients will evaluated weekly for the first month, then every two weeks forr months 2 and 3, and monthly thereafter.
Secondary	To determine changes in marrow cellularity, reticulin and fibrous content.		Bone marrow analysis will be performed at baseline and month 6.
Secondary	To determine change in cytogenetics if initially abnormal.		Cytogenetics analysis will be performed at baseline and month 6.
Secondary	To determine if quantitative change in JAK2 expression occurs as measured by quantitative pyrosequencing.		JAK2 analysis will be performed at baseline and month 3.