Dasatinib in Treating Patients With Chronic Lymphocytic Leukemia

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.

PRIMARY OBJECTIVES:

I. To estimate the biologic target activity of dasatinib in CLL patients found to have pre-treatment in vitro dasatinib cytotoxicity (as defined by a \>= 50% decrease in absolute lymphocyte count and/or bone marrow CLL count and/or lymph node or spleen size).

SECONDARY OBJECTIVES:

I. To evaluate overall objective response rates per CLL National Cancer Institute (NCI) working group.

II. To determine drug safety and tolerability of dasatinib in patients with CLL.

III. To determine overall (OS) and progression-free survival (PFS).

TERTIARY OBJECTIVES:

I. To determine if v-src avian sarcoma (Schmidt-Ruppin A-2) viral oncogene homolog (SRC), Bruton agammaglobulinemia tyrosine kinase (BTK), or tec protein tyrosine kinase (TEC) family kinase inhibition correlates with clinical response.

II. To determine which prognostic subgroups (presence of \>= 1 of the following: 11q or 17p deletion; cluster of differentiation \[CD\]38 or zeta-chain-associated protein kinase 70 \[Zap 70\] expression; unmutated immunoglobulin heavy chain \[IgVH\]) respond to dasatinib therapy.

III. To evaluate differences in baseline CLL gene expression between CLL samples that are sensitive or in-sensitive to dasatinib.

IV. To analyze changes in CLL gene expression after dasatinib treatment. V. To evaluate dasatinib pharmacokinetics. VI. To evaluate changes in type I receptor tyrosine kinase-like orphan receptor (ROR-1) expression with dasatinib treatment.

VII. To correlate response to pre-clinical IC50 in the presence/absence of HS-5 conditioned media.

VIII. To explore role of possible kinase mutations related to dasatinib response.

IX. To measure chemokines before and during treatment.

OUTLINE:

Patients receive dasatinib orally (PO) once daily (QD) during course 1 and if tolerated, twice daily (BID) in subsequent courses. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 2 years.

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