LCL161 in Treating Patients With Primary Myelofibrosis, Post-Polycythemia Vera Myelofibrosis, or Post-Essential Thrombocytosis Myelofibrosis

Inclusion Criteria:

* Patients must provide written informed consent
* Willing and able to comply with scheduled visits, treatment plan and laboratory tests
* Patient is able to swallow and retain oral medication
* Must be diagnosed with treatment requiring PMF or post ET/PV MF with intermediate-1, intermediate -2 or high risk disease according to the International Working Group (IWG) prognostic scoring system, or if with low risk disease then with symptomatic splenomegaly that is \>= 5 cm below left costal margin by physical exam
* Patients who are not candidates for, intolerant, or relapsed/refractory to ruxolitinib
* Eastern Cooperative Oncology Group (ECOG) performance status 0-2
* Absolute neutrophil count (ANC) \>= 0.5 x 10\^9/L (1500/mm\^3)
* Serum direct bilirubin =\< 2.0 x ULN (upper limit of normal)
* Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 x ULN, except for patients with MF involvement of the liver who must have AST and ALT =\< 5 x ULN
* Serum creatinine =\< 1.5 x ULN
* Treatment-related toxicities from prior therapies must have resolved to grade =\< 1
* At least 2 weeks from prior MF-directed treatment (till the start of study drug)

Exclusion Criteria:

* Any concurrent severe and/or uncontrolled medical conditions that could increase the patient's risk for toxicity while in the study or that could confound discrimination between disease- and study treatment-related toxicities
* Impaired cardiac function or clinically significant cardiac diseases, including any of the following: history or presence of ventricular tachyarrhythmia; presence of unstable atrial fibrillation (ventricular response \> 100 beats per minute \[bpm\]); patients with stable atrial fibrillation are eligible, provided they do not meet any of the other cardiac exclusion criteria; clinically significant resting bradycardia (\< 50 bpm); angina pectoris or acute myocardial infarction =\< 3 months prior to starting study drug; other clinically significant heart disease (e.g., symptomatic congestive heart failure; uncontrolled arrhythmia or hypertension; history of labile hypertension or poor compliance with an antihypertensive regimen)
* Patients who are currently receiving chronic (\> 14 days) treatment with corticosteroids at a dose \>= 10 mg of prednisone (or its glucocorticoid equivalent) per day, or any other chronic immunosuppressive treatment that cannot be discontinued prior to starting study drug
* Patients who are currently receiving treatment with agents that are metabolized solely through cytochrome P450 family 3, subfamily A, polypeptide 4/5 (CYP3A4/5) and have a narrow therapeutic index or are strong cytochrome P450 family 3, subfamily C, polypeptide 8 (CYP2C8) inhibitors; or are receiving treatment with agents that carry a risk for QT prolongation and are CYP3A substrates
* Patients with impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of LCL161 as per physicians opinion
* Pregnant or breast feeding (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive beta-human chorionic gonadotropin (HCG) laboratory test
* Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing and for 90 days after study treatment; highly effective contraception methods include: total abstinence or male partner or female sterilization or combination of any two of the following (a+b or a+c, or b+c): a) use of oral, injected or implanted hormonal methods of contraception, b) placement of an intrauterine device (IUD) or intrauterine system (IUS), c) barrier methods of contraception: condom for male partner or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository

  * Note: postmenopausal women are allowed to participate in this study; women are considered post-menopausal and not of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks ago; in the case of oophorectomy alone, a woman is considered to be of not child bearing potential only when her reproductive status has been confirmed by follow-up hormone level assessment
* Sexually active males must use a condom during intercourse while taking the drug and for 3 months after stopping study drug and should not father a child in this period; a condom is required to be used also by vasectomized men in order to prevent delivery of the drug via seminal fluid