Dasatinib in Polycythemia Vera

NCT00538980 | Terminated Phase 2 Results

• 2 other identifiers: 0701008940CA180-104
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 4

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.

Conditions

Polycythemia Vera

Keywords

Polycythemia Vera; PV; P Vera

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (3)

• Changes in Marrow Cellularity, Reticulin and Fibrous Content

  Bone marrow analysis will be performed at baseline and month 6.

• Change in Cytogenetics

  Cytogenetics analysis will be performed at baseline and month 6.

• Change in JAK2 Allele Burden

  JAK2 analysis will be performed at baseline and month 3.

Study Arms (1)

All patients

EXPERIMENTAL

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

Interventions

Dasatinib DRUG

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).

All patients

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Weill Medical College of Cornell University: lead
• Bristol-Myers Squibb: collaborator

Study Sites (4)

Emory Winship Cancer Institute

Atlanta, Georgia, 30322, United States

Location

Hematology/Oncology Associates of Rockland

New City, New York, 10956, United States

Location

Weill Cornell Medical College - New York Presbyterian Hospital

New York, New York, 10021, United States

Location

The Jones Clinic

Germantown, Tennessee, 38138, United States

Location

MeSH Terms

Conditions

Polycythemia Vera

Interventions

Dasatinib

Condition Hierarchy (Ancestors)

Bone Marrow Neoplasms; Hematologic Neoplasms; Neoplasms by Site; Neoplasms; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Myeloproliferative Disorders

Intervention Hierarchy (Ancestors)

Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines

Results Point of Contact

• Title: Richard T. Silver, MD
• Organization: Weill Cornell Medicine

rtsilve@med.cornell.edu

646-962-2273

Study Officials

• Richard T Slver, M.D.

  Weill Medical College of Cornell University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 2, 2007
• First Posted: October 3, 2007
• Study Start: April 30, 2007
• Primary Completion: August 25, 2010
• Study Completion: August 27, 2010
• Last Updated: June 20, 2017
• Results First Posted: June 20, 2017

Record last verified: 2017-05

Locations

US (4)