Dasatinib in Treating Patients With Chronic Lymphocytic Leukemia
Condition: Refractory Chronic Lymphocytic Leukemia; Stage I Chronic Lymphocytic Leukemia; Stage II Chronic Lymphocytic Leukemia; Stage III Chronic Lymphocytic Leukemia; Stage IV Chronic Lymphocytic Leukemia
MeSH terms: Leukemia; Leukemia, Lymphoid; Leukemia, Lymphocytic, Chronic, B-Cell
Intervention: Dasatinib; Laboratory Biomarker Analysis; Pharmacological Study
Intervention description: Given PO; Correlative studies; Correlative studies
Intervention MeSH terms: Dasatinib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 19.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase II trial studies how well dasatinib works in treating patients with chronic
      lymphocytic leukemia (CLL). Dasatinib may stop the growth of cancer cells by blocking some of
      the enzymes needed for cell growth.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Written informed consent and Health Insurance Portability and Accountability Act
             (HIPAA) authorization for release of personal information

          -  Eastern Cooperative Oncology Group (ECOG) =< 2

          -  In vitro dasatinib sensitivity (IC 50 =< 50 nm per MTS assay)

          -  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 defined as follows
             (1996 NCI working group):

               -  Massive or progressive splenomegaly

               -  Massive lymph nodes (>= 10 cm), 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

          -  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 corrected QT (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; women of childbearing potential must be advised of
             the importance of avoiding pregnancy during trial participation and the potential risk
             factors for an unintentional pregnancy

          -  After consent, discontinuation ("washout period") of any medications known to
             contribute significantly to the risk of QT prolongation or interfere with cytochrome
             P450, family 3, subfamily A, polypeptide 4 (CYP3A4) mediated drug metabolism

          -  Patient agrees to discontinue St. John's Wort while receiving dasatinib therapy
             (discontinue St. John's Wort at least 5 days before starting dasatinib)

          -  Patient agrees that IV bisphosphonates will be withheld for the first eight weeks of
             dasatinib therapy due to risk of hypocalcemia

          -  Patient agrees to discontinue anti-coagulants and anti-platelet drugs; note: a low
             dose aspirin regimen (81mg QD) is permitted with close monitoring of the subject's
             platelets for a level >= 50,000/mm^3

        Exclusion Criteria:

          -  Patients may not receive concurrent chemotherapy, radiotherapy, or immunotherapy

          -  Pleural or pericardial effusion of any grade

          -  Uncontrolled angina, > New York Heart Association (NYHA) class III congestive heart
             failure or myocardial infarction (MI) within 6 months prior to study enrollment

          -  Diagnosed congenital long QT syndrome

          -  Any history of clinically significant ventricular arrhythmias (such as ventricular
             tachycardia, ventricular fibrillation, or Torsades de pointes)

          -  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, including:

               -  Diagnosed congenital bleeding disorders (e.g., von Willebrand's disease)

               -  Diagnosed acquired bleeding disorder within one year (e.g., acquired anti-factor
                  VIII antibodies)

          -  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
             are eligible for the study only after principal investigator (PI) review; dose
             adjustments and/or monitoring of drug levels where applicable will be made as needed
             by the PI after consultation with pharmacy

          -  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