Dasatinib in Relapsed Chronic Lymphocytic Leukemia

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00438854
Recruitment Status : Completed
First Posted : February 22, 2007
Results First Posted : October 12, 2012
Last Update Posted : December 13, 2017
Brigham and Women's Hospital
Dana-Farber Cancer Institute
Bristol-Myers Squibb
Information provided by (Responsible Party):
Philip C. Amrein, M.D., Massachusetts General Hospital

Brief Summary:
The purpose of this research study is to see if Dasatinib is effective and safe to give to people with relapsed chronic lymphocytic leukemia (CLL) and to determine the effects of the drug on LYN kinase activity in blood and bone marrow. Recent research shows that a key enzyme in CLL cells is responsible for cell survival. This enzyme is called LYN kinase. Laboratory studies show that inhibition of LYN kinase in CLL cells results in the death to CLL cells. Dasatinib has the ability to inhibit LYN kinase and, therefore, should have some effect on CLL cells.

Condition or disease Intervention/treatment Phase
Chronic Lymphocytic Leukemia Drug: Dasatinib Phase 2

Detailed Description:
  • After the screening procedures confirm that the participant is eligible and willing to participate in the research study, they will have the following tests and procedures.
  • Dasatinib is given orally once daily. Each participant will have a pill diary to record doses and any missed doses. All necessary drug refills will be given during clinic appointments, at which time the pill diary and any unused study drug will be returned.
  • During the first month of study treatment the participant will come to the clinic at the following intervals: Day 1: An EKG will be performed two hours after the first dose of medication; Days 3-8: Blood samples will be drawn once between days 3-8; Weeks 2-4: A physical examination, EKG and blood samples will be drawn once a week.
  • Beginning with the second month of study treatment, participants will come to the clinic monthly for up to two years. The following tests and procedures will be done; physical examination (monthly), blood work (monthly), pregnancy test (monthly), EKG (monthly for 6 months, then when medically indicated), CT of the neck, chest and abdomen (every 2 months for 6 months, then once every 6 months), at the end of month 2, additional blood will be drawn for research testing.
  • Participants can continue to take the study drug for up to two years as long as their disease does not progress and they are not experiencing any serious side effects.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 15 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Study of Dasatinib (BMS-354825) in Relapsed Chronic Lymphocytic Leukemia
Study Start Date : December 2006
Actual Primary Completion Date : October 2010
Actual Study Completion Date : March 2013

Arm Intervention/treatment
Experimental: Dasatinib treatment
All patients were treated with dasatinib pills by mouth as treatment.
Drug: Dasatinib
Taken orally once daily. Participants may continue on study treatment as long as there is no disease progression or serious side effects.

Primary Outcome Measures :
  1. Overall Objective Response [ Time Frame: 2 years ]

    Overall objective response rate in terms of complete response, nodular partial response, and partial response to treatment. Objective response is when a biopsy shows. In general response is defined as the following (not complete criteria):

    Complete response (CR) requires all of the following for a period of at least 2 months:

    • Absence of lymphadenopathy
    • No hepatomegaly or splenomegaly
    • Absence of constitutional symptoms
    • Normal complete blood count

    Nodular partial response (nPR): Met the criteria for CR, but had residual bone marrow biopsy nodules as the only evidence of disease

    Partial response (PR): requires at least the following:

    • 50% decrease in peripheral blood lymphocyte count
    • 50% reduction in lymphadenopathy
    • 50% reduction in the size of the liver and/or spleen

Secondary Outcome Measures :
  1. Complete Response Rate [ Time Frame: 1 year ]
    The number of participants with a 100% reduction in nodal mass.

  2. Median Time to Disease Progression [ Time Frame: 1 year ]
    The median time to disease progression, measured from the start of treatment.

  3. Median Overall Survival [ Time Frame: 3 years ]
    The median survival time, as measured from the start of treatment until death from any cause.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • 18 years of age or older
  • CLL/SLL with cells positive by flow cytometry (or immunostaining) for CD19, CD23 and CD. Patients may be CD23 negative as long as they are also cyclin D1 negative.
  • Must have failed at least 1 prior fludarabine containing regimen or have failed at least 2 non-fludarabine containing regimens or have a contraindication to fludarabine use
  • ECOG performance status of 2 or better
  • Adequate organ function to tolerate chemotherapy
  • Adequate method of contraception

Exclusion Criteria:

  • Pregnant or breast-feeding women
  • Uncontrolled angina within 3 months
  • Diagnosed or suspected congenital long QT syndrome
  • History of clinically significant ventricular arrhythmias
  • Prolonged QTc interval on pre-entry electrocardiogram
  • Uncontrolled hypertension
  • Drugs that are generally accepted to have a risk of causing Torsades de Pointes
  • Patient known to be HIV positive
  • Known significant bleeding disorder unrelated to CLL
  • Drugs that interfere with platelet function or coagulation must be stopped at least 7 days prior to entry

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00438854

United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02115
Sponsors and Collaborators
Massachusetts General Hospital
Brigham and Women's Hospital
Dana-Farber Cancer Institute
Bristol-Myers Squibb
Principal Investigator: Philip Amrein, MD Massachusetts General Hospital

Responsible Party: Philip C. Amrein, M.D., Assistant Professor of Medicine, Massachusetts General Hospital Identifier: NCT00438854     History of Changes
Other Study ID Numbers: 06-211
CA 180-045
First Posted: February 22, 2007    Key Record Dates
Results First Posted: October 12, 2012
Last Update Posted: December 13, 2017
Last Verified: November 2017

Keywords provided by Philip C. Amrein, M.D., Massachusetts General Hospital:
LYN kinase

Additional relevant MeSH terms:
Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Leukemia, B-Cell
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action