Chronic Lymphocytic Leukemia
Conditions
Keywords
dasatinib, BMS-354825, CLL, SLL, LYN kinase
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.
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.
Interventions
DRUGDasatinib
Taken orally once daily. Participants may continue on study treatment as long as there is no disease progression or serious side effects.
Sponsors
Brigham and Women's Hospital
Dana-Farber Cancer Institute
Bristol-Myers Squibb
Massachusetts General Hospital
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Objective Response | 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
| Measure | Time frame | Description |
|---|---|---|
| Complete Response Rate | 1 year | The number of participants with a 100% reduction in nodal mass. |
| Median Time to Disease Progression | 1 year | The median time to disease progression, measured from the start of treatment. |
| Median Overall Survival | 3 years | The median survival time, as measured from the start of treatment until death from any cause. |
Countries
United States
Participant flow
Recruitment details
Started recruitment 12/2006 and ended recruitment 12/2008. Patients were recruited from the clinics of the Massachusetts General Hospital and the Dana Farber Cancer Institute.
Pre-assignment details
Patients signing the consent form were screened for eligibility. If eligible, they were started on protocol. This is a single-arm protocol.
Participants by arm
| Arm | Count |
|---|---|
| Dasatinib Treatment All patients were treated with Dasatinib pills by mouth as treatment.
Dasatinib: Taken orally once daily. Participants may continue on study treatment as long as there is no disease progression or serious side effects. | 15 |
| Total | 15 |
Baseline characteristics
| Characteristic | Dasatinib Treatment |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 6 Participants |
| Age, Categorical Between 18 and 65 years | 9 Participants |
| Age, Continuous | 60.67 years STANDARD_DEVIATION 12 |
| Region of Enrollment United States | 15 participants |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 2 / 15 |
| other Total, other adverse events | 15 / 15 |
| serious Total, serious adverse events | 10 / 15 |
Outcome results
Primary
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
Time frame: 2 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dasatinib Treatment | Overall Objective Response | 3 participants who responded |
Comparison: The primary measures of efficacy of tumor response were: complete remission (CR), nodular partial remission (nPR), or partial remission (PR), as per NCI-WG criteria. The true ORR is reported as percentage and 90% CI calculated using the binomial exact test. Time to treatment failure (TTF) was defined from the date on study to date of progression, death in remission, initiation of non-protocol therapy in the absence of progression, or censored on the last visit.
Secondary
Complete Response Rate
The number of participants with a 100% reduction in nodal mass.
Time frame: 1 year
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Dasatinib Treatment | Complete Response Rate | 0 Participants |
Secondary
Median Overall Survival
The median survival time, as measured from the start of treatment until death from any cause.
Time frame: 3 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Dasatinib Treatment | Median Overall Survival | 27 Months |
Secondary
Median Time to Disease Progression
The median time to disease progression, measured from the start of treatment.
Time frame: 1 year
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Dasatinib Treatment | Median Time to Disease Progression | 7.5 Months |