Inclusion Criteria

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.