A Phase II Study of Dasatinib in Chronic Lymphocytic Leukemia in Patients Who Exhibit in Vitro Dasatinib Sensitivity

Inclusion Criteria:

- Written informed consent and Health Insurance Portability and Accountability
Act(HIPAA)

- Age >18 years old

- Eastern Cooperative Oncology Group(ECOG) ≤2

- In vitro dasatinib sensitivity (IC 50 ≤10 nm per MTS assay); samples obtained on eIRB
4422 may be used

- Diagnosis of CLL and must meet one of the following:

- Relapsed CLL in all patients who have failed at least one prior treatment,
regardless of risk group OR

- De novo (treatment-naïve) patients age ≥65 who are not candidates for or do not
want to pursue aggressive chemotherapy treatment.

- Have indications for treatment or evidence of progressive disease(1996 NCI working
group); Massive or progressive splenomegaly, Massive lymph nodes (≥10cm), nodal
clusters (≥10 cm), or progressive lymphadenopathy, Symptomatic anemia and/or
thrombocytopenia (Rai stages III or IV disease, Autoimmune hemolytic anemia and/or
thrombocytopenia that are poorly responsive to corticosteroid therapy, Progressive
lymphocytosis with increase in lymphocyte count of >/= 50% over a 2-month period or
an anticipated doubling time of <6 months, Repeated episodes of infection

- Have not received CLL treatment within the past 2 weeks

- Have adequate organ function: Total bilirubin <2.0 x Upper Limit of Normal (ULN),
Aspartate aminotransferase (AST) ≤2.5 x ULN, Alanine aminotransferase (ALT) ≤2.5 x
ULN, Serum creatinine <2.0 x ULN, International Normalized Ratio(INR) ≤1.2,
Platelet(Plt) count > 30,000

- Ability to take oral medication (dasatinib must be swallowed whole)

- No clinically significant infections as determined by the investigator

- Normal QTc interval (<450 msec)

- Serum potassium and magnesium are within normal limits

- Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy
test (sensitivity =<25 IU HCG/L) within 72 hours prior to the start of study drug
administration.

- Persons of reproductive potential must agree to use an adequate method of
contraception throughout treatment and for at least 4 weeks after study drug is
stopped prior to study enrollment.

- After consent, discontinuation ("washout period") of any medications known to
contribute significantly to the risk of QT prolongation or interfere with Cytochrome
P(CYP3A4) mediated drug metabolism.

- Patient agrees to discontinue St. Johns Wort while receiving dasatinib therapy

- Patient agrees that IV bisphosphonates will be withheld for the first eight weeks of
dasatinib therapy

- Patient agrees to discontinue anti-coagulants and anti-platelet drugs.

Exclusion Criteria:

- Patients may not receive concurrent chemotherapy, radiotherapy, or immunotherapy.

- Pleural or pericardial effusion of any grade

- Uncontrolled angina, >NYHA class III congestive heart failure or MI within 6 months
prior to study enrollment

- Diagnosed congenital long QT syndrome

- Any history of clinically significant ventricular arrhythmias

- Prolonged QTc interval on pre-entry electrocardiogram (>450 msec)

- Subjects who are detained or imprisoned are not eligible

- History of significant bleeding disorder unrelated to cancer

- May not take concomitant medications that are generally accepted to have a risk of
causing Torsades de Pointes including: (Patients must discontinue drug 7 days prior
to starting dasatinib)quinidine, procainamide, disopyramide, amiodarone, sotalol,
ibutilide, dofetilide, erythromycin, clarithromycin, chlorpromazine, haloperidol,
mesoridazine, thioridazine, pimozide, cisapride, bepridil, droperidol, methadone,
arsenic, chloroquine, domperidone, halofantrine, levomethadyl, sparfloxacin,
lidoflazine.

- Patients already taking other CYP inducers or inhibitors other than those listed
above (and as noted in appendix F) are eligible for the study only after PI and
pharmacy review.

- Women who are unwilling or unable to use an acceptable method to avoid pregnancy for
the entire study period and for at least 4 weeks after cessation of study drug, or
have a positive pregnancy test at baseline, or are pregnant or breastfeeding