Dasatinib in Treating Patients With Chronic Lymphocytic Leukemia

This is an interventional treatment trial for Refractory Chronic Lymphocytic Leukemia Read More

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