Sorafenib, Vorinostat, and Bortezomib in Treating Patients With Acute Myeloid Leukemia

Inclusion Criteria

• A confirmed baseline diagnosis of AML by the revised guidelines of the International Working Group for AML including newly diagnosed, relapsed or refractory disease *Newly diagnosed: ** Age 70 years and older ** 60-69 years old and unfit for conventional chemotherapy * Relapsed disease: ** Age 60 years and older any time following the first relapse, if the patient is not considered candidate for or is not interested in salvage chemotherapy ** Age 18-59 years who have relapsed less than 6 months following achievement of a complete remission (defined as duration of remission from the time of documentation of complete morphologic remission to the time of documentation of relapse) * Refractory disease: ** Age 18-59 years who have failed at least two lines of conventional chemotherapy (one induction and one salvage therapy); examples include: *** Patient achieves a complete remission and receives (or does not receive) consolidation therapy, but relapses later; this patient will be eligible only if s/he fails at least one salvage therapy following relapse *** Patient demonstrates residual leukemia on post-induction day 14 bone marrow and receives salvage therapy; this patient will be eligible only if s/he fails the salvage therapy *** Patient demonstrates reasonable response on post-induction day 14 bone marrow (or the bone marrow is not performed), but the follow-up bone marrow shows residual disease; this patient will be eligible only if s/he fails at least one salvage therapy ** Age 60 and older who have failed at least one line of conventional chemotherapy, or treatment with hypomethylating agent (in the setting of poor-risk/complex karyotype) and is not considered candidate for or is not interested in salvage chemotherapy; FltITD +ve disease is not considered responsive to hypomethylating agent * Patients age 18 years and older with relapse in the form of AML after stem cell transplant will be eligible, even if they were transplanted for myelodysplastic syndromes (MDS) or myeloproliferative neoplasm (MPN)
• Poor-risk (monosomy 5,7) or complex cytogenetics profile (3 or more cytogenetic abnormalities), or deletion of chromosome 5 (-5), or deletion of chromosome 7 (-7), or positive FLT3-ITD mutation
• The patient must have discontinued all previous therapies for acute leukemia for at least 14 days and recovered from the acute non-hematologic side effects of the therapy
• Hydroxyurea to control peripheral blood blast count must be discontinued within 24 hours prior to the initiation of treatment; hydroxyurea can also be given through the first cycle of treatment, but should not be initiated earlier than day 5
• Patients must have an Eastern Cooperative Oncology Group (ECOG) (Zubrod) performance status of 0-2
• Patients must have adequate hepatic function with a total bilirubin =< 1.5 times upper limit normal (ULN) within one week prior to treatment
• Patients must have adequate hepatic function with alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 2.5 times ULN within one week prior to treatment
• Patients must have adequate renal function as defined by a serum creatinine =< 1.5 times ULN within one week prior to treatment
• Female patients must meet 1 of the following: * Postmenopausal for at least 1 year before the screening visit, or * Surgically sterile (have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy), or * Females of childbearing potential must agree to practice effective method of contraception from the time of signing the informed consent form through 30 days after the last treatment dose, or agree to completely abstain from heterosexual intercourse
• Male patients, even if surgically sterilized (ie, status post vasectomy) must agree to 1 of the following: * Practice effective barrier contraception during the entire study treatment period and through a minimum of 30 days after the last dose of study drug, or completely abstain from heterosexual intercourse
• Patients must be able to swallow and tolerate oral medications
• Patients must have the ability to understand and voluntarily sign a written informed consent; if an unexpected non-English speaking patient or if an illiterate patient is encountered, current Institutional Review Board (IRB) guidelines on obtaining informed consent will be followed; a voluntary written informed consent must be obtained before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care

Exclusion Criteria

• Known central nervous system (CNS) leukemia by spinal fluid cytology, flow cytometry or imaging; a lumbar puncture is not required unless CNS involvement is clinically suspected; patients with signs or symptoms of leukemic meningitis must have a negative lumbar puncture within 2 weeks of study enrollment
• Diagnosis of acute promyelocytic leukemia (APL)
• Grade >= 2 peripheral neuropathy
• Serious illness including, significant ongoing or active infection, New York Heart Association (NYHA) grade III or IV congestive heart failure, unstable angina (anginal symptoms at rest) or new onset angina (began within the last 3 months) or myocardial infarction within the past 6 months, cardiac ventricular arrhythmias requiring anti-arrhythmic therapy, thrombotic or embolic events such as a cerebrovascular accident including transient ischemic attacks within past 3 months; serious medical or psychiatric illness/social situations that in the opinion of the investigator would limit compliance with study requirements
• Diagnosed or treated for another malignancy within 3 years of enrollment, with the exception of complete resection of basal cell carcinoma or squamous cell carcinoma of the skin, an in situ malignancy, or low-risk prostate cancer after curative therapy
• Active corneal erosions or history of abnormal corneal sensitivity test
• Known or suspected history of severe hypersensitivity reaction to tyrosine kinase inhibitors, histone deacetylase inhibitors, proteosome inhibitors, boron, or mannitol
• Female patients who are lactating or have a positive serum pregnancy test within 72 hours of initiation of treatment, or a positive urine pregnancy test on day 1 before first dose of study drug, if applicable; pregnancy testing is not required for postmenopausal or surgically sterilized women
• Concurrent use of other histone deacetylase inhibitors (e.g. valproic acid) are prohibited except for histone deacetylase (HDAC) inhibitors or HDAC-inhibitor like agents used for non-cancer treatment (e.g. epilepsy), where a 14 day washout is allowed
• Participation in clinical trials with other investigational agents not included in this trial, within 14 days of the start of this trial and throughout the duration of this trial
• Radiation therapy within 3 weeks before randomization; enrollment of subjects who require concurrent radiotherapy (which must be localized in its field size) should be deferred until the radiotherapy is completed and 3 weeks have elapsed since the last date of therapy
• Patients with known human immunodeficiency virus (HIV), or known active hepatitis B or C infections