PCI-32765 (Ibrutinib) in Treating Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma, or B-cell Prolymphocytic Leukemia

This is a Phase II, single institution open-label, non-randomized monotherapy study to evaluate the clinical efficacy and durable disease control of PCI-32765 administered to patients with relapsed/refractory CLL/SLL/PLL of all risk categories with patients having deletion 17p13 independently evaluated.

This is a clinical trial, a type of research study, involving treatment with an investigational (experimental) drug called PCI-32765 (Ibrutinib), a "kinase inhibitor". "Kinases" are proteins that are inside of cells and help them to live and grow. The specific kinase inhibited or blocked by this study drug is believed to help blood cancer cells grow and live. By inhibiting or "blocking" the activity of this kinase, it is possible that the study drug may be able to kill the cancer cells or stop them from growing. This study will involve treating patients with chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), or B-cell prolymphocytic leukemia (B-PLL) that has not responded to or has relapsed after standard treatment. This trial is studying how effective PCI-32765 is at treating CLL, SLL, or B-PLL and all the effects, good and/or bad, treatment with this drug has on patients and their cancers.

Eligibility Criteria:
Inclusion Criteria:

* Confirmed diagnosis of relapsed/refractory CLL/SLL who require treatment and have failed at least one prior therapy.
* Patients must have available results of interphase cytogenetics CLL fluorescent in situ hybridization (FISH) panel; the cytogenetic analysis must be done prior to starting therapy but after any recent therapy
* Eastern Cooperative Oncology Group (ECOG) performance status =\< 2
* Life expectancy greater than 2 months
* Bilirubin =\< 1.5 X the institutional upper limit of normal unless due to Gilbert's disease or disease related to Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) =\< 2.5 X the institutional upper limit of normal unless disease related
* Creatinine =\< 1.5 X the institutional upper limit of normal unless disease related
* Absolute neutrophil count (ANC) \>= 0.75 X 10\^9/L
* Platelet count \>= 30 X 10\^9/L
* Agree to use contraception during the study and for 30 days after the last dose of study drug if sexually active and able to bear children
* Ability to understand and the willingness to sign a written informed consent document
* Patients with uncontrolled or active infection requiring antibiotic therapy; patients with controlled infections who are receiving extended antibiotics or prophylactic therapy are not excluded

Exclusion Criteria:

* Patients who have had chemotherapy, radiotherapy or immunotherapy within 4 weeks prior to the first dose of study drug (corticosteroids for disease-related symptoms allowed but doses equivalent to \> 20 mg prednisone orally per day require 1 week washout before study drug administration or steroid dose must be equal to =\< 20 mg prednisone orally daily)
* Patients who have not recovered from adverse events of \>= grade 3 toxicity due to agents administered more than 4 weeks ago
* Receiving any other investigational agents
* Previously randomized to any PCI-32765 clinical trial
* Known secondary malignancy that limits survival to less than two years
* Patients with malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel or ulcerative colitis, symptomatic inflammatory bowel disease, or partial or complete bowel obstruction
* Patients requiring anti-coagulation with warfarin or other Vitamin K antagonists or heparin products including low molecular weight heparin (LMWH)
* Currently active, clinically significant hepatic impairment Child-Pugh class B or C according to the Child Pugh classification
* Patients requiring treatment with a strong cytochrome P450 3A4/5 (CYP3A4/5) and/or cytochrome P450 2D6 (CYP2D6) inhibitor
* Patients with a life-threatening illness, medical condition or organ system dysfunction which, in the investigator's opinion, could compromise the subject's safety, interfere with the absorption or metabolism of PCI-32765 PO, or put the study outcomes at undue risk
* Significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of screening, or any Class 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification
* Active central nervous system (CNS) involvement by lymphoma
* Pregnant or women who are breastfeeding