Dasatinib in Relapsed Chronic Lymphocytic Leukemia

This study has been completed.
Sponsor:
Collaborators:
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
ClinicalTrials.gov Identifier:
NCT00438854
First received: February 20, 2007
Last updated: April 23, 2013
Last verified: April 2013
  Purpose

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 Intervention Phase
Chronic Lymphocytic Leukemia
Drug: Dasatinib
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Study of Dasatinib (BMS-354825) in Relapsed Chronic Lymphocytic Leukemia

Resource links provided by NLM:


Further study details as provided by Massachusetts General Hospital:

Primary Outcome Measures:
  • Overall Objective Response Rate in Terms of Complete Response, Nodular Partial Response, and Partial Response to Treatment With Dasatinib for Patients With CLL/SLL (Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma). [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • The Complete Response Rate Will Also be Evaluated [ Time Frame: TBD ] [ Designated as safety issue: No ]
  • Duration of Overall Response for All Patients [ Time Frame: TBD ] [ Designated as safety issue: No ]
  • to Determine the Progression-free Survival and Overall Survival [ Time Frame: TBD ] [ Designated as safety issue: No ]
  • to Define the Spectrum of Toxicities of This Treatment in This Patient Population [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
  • and to Correlate LYN Kinase Activity With Response in Study Subjects. [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Enrollment: 15
Study Start Date: December 2006
Study Completion Date: March 2013
Primary Completion Date: October 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

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.
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00438854

Locations
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
Investigators
Principal Investigator: Philip Amrein, MD Massachusetts General Hospital
  More Information

No publications provided

Responsible Party: Philip C. Amrein, M.D., Assistant Professor of Medicine, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT00438854     History of Changes
Other Study ID Numbers: 06-211, CA 180-045
Study First Received: February 20, 2007
Results First Received: April 25, 2012
Last Updated: April 23, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Massachusetts General Hospital:
dasatinib
BMS-354825
CLL
SLL
LYN kinase

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

ClinicalTrials.gov processed this record on September 18, 2014