Dasatinib in Relapsed Chronic Lymphocytic Leukemia

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Chronic Lymphocytic Leukemia

Intervention / Treatment
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* Drug: Dasatinib


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CLL, SLL, dasatinib, BMS-354825, LYN kinase