Pacritinib and Chemotherapy in Treating Patients With Acute Myeloid Leukemia and FLT3 Mutations

Inclusion Criteria:

* Patients with AML and the presence of FLT3 mutation
* Patients with secondary AML or therapy related disease (t-AML) are eligible
* If the patient has co-morbid medical illness, life expectancy attributed to this must be greater than 6 months
* Eastern Cooperative Oncology Group (ECOG) performance status =\< 2
* Total bilirubin \< 2.0mg/dL unless due to Gilbert's disease
* Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) \< 2.5 X institutional upper limit of normal
* Creatinine (Cr) clearance \> 50 mL/min by Cockcroft-Gault calculation
* New York Heart Association (NYHA) congestive heart failure (CHF) class II or better
* Cardiac ejection fraction \>= 50% for Arm A, \>= 40% for Arm B
* Female patients of child-bearing potential must agree to use dual methods of contraception and have a negative serum pregnancy test at screening, and male patients must use an effective barrier method of contraception if sexually active with a female of child-bearing potential; acceptable methods of contraception are condoms with contraceptive foam, oral, implantable or injectable contraceptives, contraceptive patch, intrauterine device, diaphragm with spermicidal gel, or a sexual partner who is surgically sterilized or post-menopausal; for both male and female patients, effective methods of contraception must be used throughout the study and for three months following the last dose
* Ability to understand and willingness to sign the written informed consent document
* Human immunodeficiency virus (HIV) infection without history of acquired immune deficiency syndrome (AIDS) and sufficiently high cluster of differentiation (CD)4 cells (\> 400/mm\^3) and low HIV viral loads (\< 30,000 copies/ml plasma) not requiring anti-HIV therapy are eligible

Exclusion Criteria:

* Patients with core-binding factor AML (inv\[16\], t\[8;21\]) or t(15;17)
* Patients who have had chemotherapy or radiotherapy within 2 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study; treatment with hydroxyurea is permitted during cycle 1 to maintain white blood cell (WBC) \< 40,000/uL
* Patients receiving any other investigational agents or patients that have received other investigational agents within 14 days of enrollment
* Patients with active central nervous system (CNS) malignancy
* Major surgery within 2 weeks before day 1
* Uncontrolled active infection; patients with infection requiring parenteral antibiotics are eligible if the infection is controlled
* Patients with significantly diseased or obstructed gastrointestinal tract
* Uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure (New York Heart Association \[NYHA\] class III or IV), unstable angina pectoris, myocardial infarction within 6 months prior to enrollment, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities; prior to study entry, any electrocardiogram (ECG) abnormality at screening has to be documented by the investigator as not medically relevant
* Patients with serious medical or psychiatric illness likely to interfere with participation in this clinical study
* Pregnant women or women who are breastfeeding are excluded from this study; confirmation that the subject is not pregnant must be established by a negative serum beta-human chorionic gonadotropin (beta-hCG) pregnancy test result obtained during screening; pregnancy testing is not required for post-menopausal or surgically sterilized women
* Patients with advanced malignant solid tumors
* Patients who are not able to swallow capsules or tablets
* Patients with baseline corrected QT (QTc) \> 500 ms