Ibrutinib in Treating Patients With Relapsed Hairy Cell Leukemia

Inclusion Criteria:

* Histologically confirmed diagnosis of hairy cell leukemia or variant according to World Health Organization (WHO) criteria with any of the following indications for therapy:

  * Hemoglobin \< 11 g/dL
  * Platelet count \< 100,000/mL
  * Absolute neutrophil count \< 1,000/mL
  * Progressive or symptomatic splenomegaly or hepatomegaly
  * Enlarging lymphadenopathy \>= 2 cm
  * Absolute lymphocyte count \> 5,000/mL
  * Disease related constitutional symptoms consisting of unexplained weight loss exceeding 10% of body weight over the preceding 6 months, Cancer Therapy Evaluation Program (CTEP) active version of the Common Terminology Criteria for Adverse Events (CTCAE) grade 2 or 3 fatigue, fevers \> 100.5 degrees Fahrenheit (F) or night sweats for greater than 2 weeks without evidence of infection
* Patients with classic hairy cell leukemia may receive therapy under the following conditions:

  * After at least 1 prior purine nucleoside analog-containing regimen (fludarabine, pentostatin, or cladribine), or
  * Relapsed or de novo disease if deemed medically unfit for therapy with a purine nucleoside analog

    * Because there is no recognized standard of care for patients with variant hairy cell leukemia, both previously treated and previously untreated patients with this diagnosis will be eligible
* Age ≥ 18 years. Because no dosing or adverse event data are currently available on the use of ibrutinib in patients \< 18 years of age, children are excluded from this study, but may be eligible for future pediatric trials
* Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 (Karnofsky \>= 60%)
* Life expectancy of greater than 12 months
* Creatinine =\< 2.0 mg/dL, and/or creatinine clearance (estimated glomerular filtration rate \[GFR\] \[Cockcroft-Gault\]) \>= 30 mL/min
* Total bilirubin =\< 1.5 x upper limit of normal (ULN) (unless disease related or due to Gilbert's disease)
* Aspartate aminotransferase (AST) =\< 3.0 x ULN (unless disease related)
* Prothrombin time (PT)/international normalized ratio (INR) \< 1.5 x ULN
* Partial thromboplastin time (PTT) (activated partial thromboplastin time \[aPTT\]) \< 1.5 x ULN
* Because patients with HCL are typically pancytopenic at presentation for treatment, patients will be eligible without respect to baseline peripheral blood cell counts if they otherwise meet inclusion criteria
* The effects of ibrutinib on the developing human fetus are unknown; for this reason, and because tyrosine kinase inhibitors may be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry; female patients who are of non-reproductive potential (i.e., post-menopausal by history - no menses for \>= 1 year; or history of hysterectomy; or history of bilateral tubal ligation; or history of bilateral oophorectomy); female patients of childbearing potential must have a negative serum pregnancy test upon study entry; male and female patients who agree to use highly effective methods of birth control (e.g., condoms, implants, injectables, combined oral contraceptives, some intrauterine devices \[IUDs\], complete sexual abstinence, or sterilized partner) during the period of therapy and for 90 days after the last dose of study drug; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately
* Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

* Chemotherapy =\< 21 days prior to first administration of study treatment and/or monoclonal antibody =\< 6 weeks prior to first administration of study treatment
* Patients who are receiving any other investigational agents
* Patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events
* History of allergic reactions attributed to compounds of similar chemical or biologic composition as ibrutinib
* Ibrutinib is extensively metabolized by CYP3A4/5; patients who received a strong cytochrome P450 (CYP) 3A inhibitor within 7 days prior to the first dose of ibrutinib or patients who require continuous treatment with a strong CYP3A inhibitor; therefore, any medications or substances that are strong inhibitors of CYP3A4/5 should be discontinued; patients unable to change these medications must be excluded from participation; because the lists of these agents are constantly changing, it is important to regularly consult a frequently-updated list; medical reference texts such as the Physicians' Desk Reference may also provide this information; as part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product
* Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements; recent infections requiring systemic treatment need to have completed therapy \> 14 days before the first dose of study drug
* Pregnant women are excluded from this study because ibrutinib is a tyrosine kinase inhibitor with the potential for teratogenic or abortifacient effects; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with ibrutinib, breastfeeding should be discontinued if the mother is treated with ibrutinib
* Human immunodeficiency virus (HIV)-positive patients will be eligible unless they have been previously diagnosed with an acquired immune deficiency syndrome (AIDS)-defining illness
* Patients who require anticoagulation with warfarin (Coumadin) or who have taken warfarin within 28 days prior to enrollment are not eligible due to a potential increased risk of hemorrhage; patients who are currently taking vitamin K antagonists are also ineligible for this study
* Patients requiring daily corticosteroids at a prednisone equivalent of \>= 20 mg daily should not be enrolled; if corticosteroids can be discontinued (or reduced to \< 20 mg per day of prednisone or equivalent), the discontinuation or dose reduction should be done at least 7 days prior to first dose
* Prior exposure to a Bruton's tyrosine kinase (BTK) inhibitor
* Major surgery within 4 weeks of first dose of study drug
* A history of prior malignancy, with the exception of the following:

  * Malignancy treated with curative intent and with no evidence of active disease present for more than 3 years prior to screening, and felt to be at low risk for recurrence by the treating physician
  * Adequately treated non-melanomatous skin cancer or lentigo maligna melanoma without current evidence of disease
  * Adequately treated cervical carcinoma in situ without current evidence of disease
* Currently active clinically significant cardiovascular disease such as: uncontrolled arrhythmia, congestive heart failure, or class 3 or 4 congestive heart failure as defined by the New York Heart Association Functional Classification or history of myocardial infarction, unstable angina, or acute coronary syndrome within 6 months prior to first dose with study drug
* Patient is unable to swallow capsules, or has disease significantly affecting gastrointestinal function or resection of the stomach or small bowel, or symptomatic inflammatory bowel disease or ulcerative colitis, or partial or complete bowel obstruction
* History of stroke or intracranial hemorrhage within 6 months prior to enrollment
* Serologic status reflecting active hepatitis B or C infection; patients that are positive for hepatitis B core antibody, hepatitis B surface antigen (HBsAg), or hepatitis C antibody must have a negative polymerase chain reaction (PCR) prior to enrollment; (PCR positive patients will be excluded)
* Concurrent systemic immunosuppressant therapy other than corticosteroids (e.g., cyclosporine A, tacrolimus, etc.) within 28 days of the first dose of study drug
* Vaccinated with live, attenuated vaccines within 4 weeks of first dose of study drug
* Unresolved toxicities from prior anti-cancer therapy, defined as having not resolved to Common Terminology Criteria for Adverse Event (CTCAE, version 5), grade =\< 1, or to the levels dictated in the inclusion/exclusion criteria with the exception of alopecia
* Known bleeding disorders (e.g., von Willebrand's disease) or hemophilia
* Unwilling or unable to participate in all required study evaluations and procedures
* Currently active, clinically significant hepatic impairment (\>= moderate hepatic impairment according to the National Cancer Institute \[NCI\]/Child Pugh classification)
* Incarceration at time of enrollment; prisoners will be excluded from enrollment; subjects who become incarcerated after starting study treatment will be allowed to continue in the study