Therapy of Chronic Lymphocytic Leukemia With Dasatinib (BMS-354825)
Therapy of Chronic Lymphocytic Leukemia With Dasatinib (BMS-354825)
The goal of this clinical research study is to learn if dasatinib can help to control Chronic
 Lymphocytic Leukemia (CLL). The safety of the drug will also be studied.

 Optional Procedures: You will be asked to have additional blood samples drawn. These samples
 will be used to see how the disease is responding to the drug.
Dasatinib is designed to interfere with a type of protein that appears to be important for
 the survival of CLL cells.

 If you are found to be eligible to take part in this study, you will take dasatinib by mouth
 twice a day. You will be instructed to take dasatinib in the morning and in the evening.

 You will have an electrocardiogram (ECG-a test of the electrical activity of your heart) and
 a physical exam once every 3 months while on study. Blood (about 2-3 teaspoons) will be drawn
 for routine tests once a week for 1 month and then once a month for the rest of your
 treatment on this study. A bone marrow biopsy and aspiration will be performed, as needed, to
 check the status of the disease. To collect a bone marrow aspirate and biopsy, an area of the
 hip or chest bone is numbed with anesthetic, and a small amount of bone marrow and bone is
 withdrawn through a large needle.

 Dasatinib will be given for as long as you are responding. You will be taken off study if the
 disease gets worse or intolerable side effects occur.

 This is an investigational study. Dasatinib is not FDA-approved for CLL, and it has been
 authorized for use in research only. Up to 25 patients will take part in this multicenter
 study. Up to 25 will be enrolled at M. D. Anderson.

 Optional Procedures: If you agree, blood samples (about 2 tablespoons each time) will be
 collected before therapy starts, at 3-4 hours after the first dose, and at 3 months on
 therapy. These blood draws will be done when other routine tests are done. No additional
 needle sticks will be needed. The blood will be used to see how the disease is responding to
 the drug.

 You do not have to agree to take part in the optional procedures in order to receive
 treatment on this study.
Inclusion Criteria:

 1. Diagnosis of CLL, Small lymphocytic lymphoma (SLL), or -cell prolymphocytic leukemia
 (T-PLL).

 2. Previously treated with chemotherapy or monoclonal antibodies.

 3. All patients with Rai stage III-IV are eligible. - OR - Patients with Rai stage 0-II
 who meet one or more indication for treatment as defined by the NCI-sponsored Working
 Group are eligible:Massive or progressive splenomegaly; Massive lymph nodes, nodal
 clusters, or progressive lymphadenopathy; Grade 2 or 3 fatigue, fever >/= 100.5
 degrees F, night sweats for > 2 weeks w/o documented infection, presence of weight
 loss >/= 10% over the preceding 6 months; Progressive lymphocytosis with increase in
 lymphocyte count of >/= 50% over a 2-month period or an anticipated doubling time of <
 6 months.

 4. Serum bilirubin less than 2mg/dL, serum creatinine less than 2mg/dL unless abnormality
 is considered due to CLL by investigator.

 5. The Eastern Cooperative Oncology Group (ECOG) Performance Status < 3.

 6. Patients must sign an informed consent indicating they are aware of the
 investigational nature of this study, in keeping with the policies of the hospital.

 7. Sexually active women of childbearing potential must use birth control during study in
 manner that risk of failure is minimized. Prior to study enrollment women of
 childbearing potential must be advised of importance of avoiding pregnancy during
 trial and potential risk factors for unintentional pregnancy. MUST have negative
 pregnancy test. If pregnancy test is positive patient must not receive investigational
 product and must not be enrolled in study. Men enrolled on study should understand
 risks to sexual partner of childbearing potential and practice effective birth
 control.

 8. Inclusion of women and minorities: As per NIH policy, women and members of minorities
 will be included in this protocol as they are referred in the relevant populations.
 There are no exclusions of women or minorities based on the study objectives.

 9. New York Heart Association (NYHA) Class < 3

 10. Patients must sign informed consent.

 Exclusion Criteria:

 1. Pregnant or breast-feeding women are excluded.

 2. Patients may not receive concurrent chemotherapy, radiotherapy, or immunotherapy.
 Localized radiotherapy to an area not compromising bone marrow function does not
 apply, nor do hematopoietic growth factors such as erythropoietin, G-CSF, GM-CSF etc.

 3. Patients must not have untreated or uncontrolled life-threatening infection.

 4. Uncontrolled angina within 3 months; diagnosed or suspected congenital long QT
 syndrome; any history of clinically significant ventricular arrhythmias; prolonged QTc
 interval (> 450 msec); uncontrolled hypertension; significant bleeding disorder
 unrelated to cancer; patients currently taking drugs that are generally accepted to
 have a risk of causing Torsades de Pointes.

 5. Medications that inhibit platelet function (i.e., aspirin, dipyridamole, epoprostenol,
 eptifibatide, clopidogrel, cilostazol, abciximab, ticlopidine, and any non-steroidal
 anti-inflammatory drug) or Anticoagulants (warfarin, heparin/low molecular weight
 heparin [e.g., danaparoid, dalteparin, tinzaparin, enoxaparin]).