Dasatinib in Relapsed Chronic Lymphocytic Leukemia

Phase II Study of Dasatinib (BMS-354825) in Relapsed Chronic Lymphocytic Leukemia

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.

Study Overview

• Status: Completed
• Conditions: Chronic Lymphocytic Leukemia
• Intervention / Treatment: Drug: Dasatinib

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
• Enrollment (Actual): 15
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Dana-Farber Cancer Institute
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital

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:

• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Objective Response	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	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete Response Rate	The number of participants with a 100% reduction in nodal mass.	1 year
Median Time to Disease Progression	The median time to disease progression, measured from the start of treatment.	1 year
Median Overall Survival	The median survival time, as measured from the start of treatment until death from any cause.	3 years

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital
• Collaborators: Bristol-Myers Squibb; Dana-Farber Cancer Institute; Brigham and Women's Hospital
• Investigators: Principal Investigator: Philip Amrein, MD, Massachusetts General Hospital

Study record dates

Study Major Dates

• Study Start: December 1, 2006
• Primary Completion (Actual): October 1, 2010
• Study Completion (Actual): March 1, 2013

Study Registration Dates

• First Submitted: February 20, 2007
• First Submitted That Met QC Criteria: February 20, 2007
• First Posted (Estimate): February 22, 2007

Study Record Updates

• Last Update Posted (Actual): December 13, 2017
• Last Update Submitted That Met QC Criteria: November 15, 2017
• Last Verified: November 1, 2017

More Information

Terms related to this study

• Keywords: CLL; dasatinib; SLL; BMS-354825; LYN kinase
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Leukemia, B-Cell; Leukemia; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Lymphoid; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Dasatinib
• Other Study ID Numbers: 06-211; CA 180-045