Phase I Combination of Midostaurin, Bortezomib, and Chemo in Relapsed/Refractory Acute Myeloid Leukemia

Inclusion Criteria * Patients age \>18 with relapsed or refractory acute myeloid leukemia by WHO criteria are eligible for dose levels 1 and 2. Patients age \>18 and ≤ 70 with relapsed or refractory acute myeloid leukemia by WHO criteria are eligible for dose levels 3 through 6. Patients with secondary 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 * Patients must have adequate organ function as defined below: * total bilirubin \<2.0mg/dL or ≤1.5 ULN(institutional upper limit of normal) * AST(aspartate aminotransferase)(SGOT)/ALT(Alanine aminotransferase) (SGPT) \<2.5 X institutional ULN * creatinine \<1.7 mg /dL * Women of child-bearing potential and men must agree to use adequate contraception (hormonal or 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. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately * Ability to understand and willingness to sign the written informed consent document * Patients must have recovered from the toxicity of prior therapy to less than Grade 2 * Patients status post prior hematopoietic stem cell transplantation are eligible 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 until initiation of treatment on the study * 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 midostaurin, bortezomib, mitoxantrone, etoposide or cytarabine that are not easily managed. Patient has a hypersensitivity to bortezomib, boron, or mannitol. * 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. Prior to study entry, any ECG abnormality at screening has to be documented by the investigator as not medically relevant. * Ejection fraction \<50% * 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. * 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 HIV infection (due to concern for increased toxicity with the regimen in combination with HAART) or active viral hepatitis. * Patients with any pulmonary infiltrate including those suspected to be of infectious origin. In particular, patients with resolution of clinical symptoms of pulmonary infection but with residual pulmonary infiltrates on chest x-ray are not eligible until pulmonary infiltrates have completely resolved. * Patients who have had any surgical procedure, excluding central venous catheter placement or other minor procedures (e.g. skin biopsy) within 14 days of Day 1. * 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 midostaurin. * Patients with prior midostaurin treatment are excluded.