Bortezomib, Sorafenib Tosylate, and Decitabine in Treating Patients With Acute Myeloid Leukemia

• Patients must have histologically or cytologically confirmed acute myeloid leukemia (AML) by World Health Organization (WHO) criteria in the blood and/or marrow AND age >= 60 and not candidates/refuse standard induction treatment OR who have one of the following: poor risk cytogenetics, AML following antecedent hematologic disorder, or therapy-related AML
• Patients with relapsed or refractory AML age >= 18 years are also eligible for treatment; patients may have been treated for antecedent hematologic disorder with myeloid growth factors, recombinant erythropoietin, thalidomide, lenalidomide, 5-azacitidine or the 5 day schedule of decitabine; patients who have received the 10 day schedule of decitabine for treatment an antecedent hematologic disorder or AML are not 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 \< 2.0 mg/dL
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transferase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transferase [SGPT]) \< 2.5 X institutional upper limit of normal
• Creatinine \< 2.0 mg/dL or creatinine clearance (CrCl) >= 60 mL/min
• Prothrombin time (PT)/international normalized ratio (INR) monitoring, \< 1.5 x institutional upper limits of normal
• Both women and men must agree to use adequate contraception (barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; if the patient does not agree, the patient is not eligible
• Ability to understand and willingness to sign the written informed consent document

Exclusion Criteria:

• Patients who have had chemotherapy or radiotherapy within 2 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study; hydroxyurea may be administered for count control both pre-treatment and during cycle 1 only
• 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 disease or with granulocytic sarcoma as sole site of disease
• Patients with a history of allergic reactions attributed to compounds of similar chemical or biologic composition to sorafenib, bortezomib or decitabine that are not easily managed
• Uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, serious cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements; as infection is a common feature of AML, patients with active infection are permitted to enroll provided that the infection is under control; myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) class III or IV heart failure, uncontrolled angina, uncontrolled hypertension, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities
• Patients with serious medical or psychiatric illness likely to interfere with participation in this clinical study
• Patients with pre-existing grade 2 or higher neuropathy or other serious neurologic toxicity that would significantly increase risk of complications from bortezomib therapy are excluded
• Patients with a known confirmed diagnosis of human immunodeficiency virus (HIV) infection who are taking chronic anti-retroviral therapy (HAART) are ineligible if there is a potential for drug-drug interactions with the chemotherapeutic agents; patients with a known confirmed diagnosis of HIV infection who meet standard eligibility criteria and are not taking HAART with a potential for drug-drug interactions are eligible
• Patients with advanced malignant solid tumors are excluded
• Patients with known impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of sorafenib
• Patients who are taking concomitant medications that in the investigator's opinion are strong inducers of the cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) enzymes and therefore likely to interact with the study agents, will not be eligible