Ibrutinib for the Treatment of COVID-19 in Patients Requiring Hospitalization

Inclusion Criteria:

* History or active diagnosis of cancer (solid or hematologic) or precursor of cancer (monoclonal gammopathy of undetermined significance \[MGUS\]), monoclonal B lymphocytosis (MBL), aplastic anemia or myelodysplastic syndrome) that is associated with immune suppression
* Hospitalization for confirmed polymerase chain reaction (PCR) positive COVID-19 infection
* Patients with evidence of pulmonary involvement who meet any of the followings; presence of infiltrates on chest X-ray or computed tomography (CT) scan or need for supplemental oxygen \< 8 L nasal cannula or pulse oximetry \< 94% on room air
* Creatinine clearance \>= 25 ml/min by Cockcroft-Gault equation
* Total bilirubin =\< 1.5 x upper limit of normal (ULN) unless bilirubin rise is due to Gilbert's syndrome or of non-hepatic origin
* Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =\< 3 x ULN
* Absolute neutrophil count (ANC) \>= 1000/mm\^3 independent of growth factor support
* Platelets \>= 50,000/mm\^3
* Ability to swallow capsules
* Ability to provide informed consent indicating that they understand the purpose of and procedures required for the study, including biomarkers, and are willing to participate in the study
* Women of childbearing potential and men who are sexually active must be practicing a highly effective method of birth control during and after the study consistent with local regulations regarding the use of birth control methods for subjects participating in clinical trials. Men must agree to not donate sperm during and after the study. For females, these restrictions apply for 1 month after the last dose of study drug. For males, these restrictions apply for 3 months after the last dose of study drug
* Women of childbearing potential must have a negative serum (beta-human chorionic gonadotropin \[beta-hCG\]) or urine pregnancy test at screening. Women who are pregnant or breastfeeding are ineligible for this study

Exclusion Criteria:

* New-onset malignancy requiring urgent initiation of systemic chemotherapy
* Active uncontrolled systemic bacterial or fungal or other viral infection
* Requires anticoagulation with warfarin or equivalent vitamin K antagonists (e.g., phenprocoumon)
* Currently receiving BTK inhibitor therapy
* Actively receiving anti-cancer therapy (other than hormonal therapies). All anti-cancer therapy (except hormonal therapies) must be stopped at the time of screening; can be resumed as soon as ibrutinib is discontinued. Significantly T cell suppressive chemotherapy (defined as requiring PJP prophylaxis per standard guidelines) is not allowed for 3 months prior to enrollment.
* Clinically significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of screening, or any class 3 (moderate) or class 4 (severe) cardiac disease as defined by the New York Heart Association Functional classification requirement for mechanical ventilation at screening
* Known bleeding disorders (e.g., Von Willebrand's disease, platelet storage pool disorders, or hemophilia)
* Stroke or intracranial hemorrhage within 6 months of screening
* Major surgery or non-healing wound within 4 weeks of enrollment
* Concomitant administration of prohibited medications
* Known history of human immunodeficiency virus (HIV), or active hepatitis B or C infection
* Disease significantly affecting gastrointestinal function and/or inhibiting small intestine absorption (malabsorption syndrome, resection of the small bowel, poorly controlled inflammatory bowel disease, etc.)
* Requires chronic treatment with strong CYP3A inhibitors