Inclusion Criteria:

- Diagnosis of acute myeloid leukemia (AML) according to WHO classification

- At least 5% blasts in the bone marrow

- With or without extramedullary disease

- To be eligible for the dose-finding phase (closed as of 10/10) :

- Relapsed patients must meet the following criteria:

- Must have had a prior diagnosis of AML, but may NOT have inv(16) or t(8;21)
cytogenetics

- May be in first or any subsequent relapse

- If in first relapse, remission duration must be less than one year

- Refractory patients must meet the following criteria:

- Must have had a prior diagnosis of AML

- May have received one or more attempt at remission induction

- Patients with treatment-related AML may be previously treated or untreated for
secondary AML

- To be eligible for the efficacy phase:

- Relapsed patients must meet the following criteria:

- Must have had a prior diagnosis of AML, with no restriction on prior
cytogenetics

- Must be in first relapse

- Must not have received prior reinduction therapy

- Refractory patients must meet the following criteria:

- Must have had a prior diagnosis of AML

- Must not have received more than one attempt at remission induction (which
may consist of up to two therapy courses)

- Patients with treatment-related AML must be previously untreated for secondary
AML

- No juvenile myelomonocytic leukemia or acute promyelocytic leukemia (APL; FAB M3)

- Patients with the following CNS status are eligible only in the absence of neurologic
symptoms suggestive of CNS leukemia, such as cranial nerve palsy:

- CNS 1, defined as absence of blasts in cerebral spinal fluid (CSF) on cytospin
preparation, regardless of the number of WBCs

- CNS 2, defined as presence of < 5/μL WBCs in CSF and cytospin positive for
blasts, or > 5/uL WBCs but negative by Steinherz/Bleyer algorithm:

- CNS 2a: < 10/μL RBCs; < 5/μL WBCs and cytospin positive for blasts

- CNS 2b: ≥ 10/μL RBCs; < 5/μL WBCs and cytospin positive for blasts

- CNS 2c: ≥ 10/μL RBCs; ≥ 5/μL WBCs and cytospin positive for blasts but
negative by Steinherz/Bleyer algorithm

- Patients with CNS3 disease (presence of ≥ 5/μL WBCs in CSF and cytospin positive for
blasts [in the absence of a traumaticlumbar puncture] and/or clinical signs of CNS
leukemia) are not eligible

- CNS toxicity ≤ grade 2

- Lansky (patients ≤ 16 years of age) or Karnofsky (patients > 16 years of age)
performance status (PS) 50-100%

- ECOG PS 0-2

- No Down syndrome

- No Fanconi anemia, Kostmann syndrome, Shwachman syndrome, or any other known bone
marrow failure syndrome

- No evidence of active graft-vs-host disease

- Creatinine clearance or radioisotope glomerular filtration rate ≥ 70 mL/min OR serum
creatinine based on age/gender as follows:

- 0.4 mg/dL for patients 1 month to < 6 months of age

- 0.5 mg/dL for patients 6 months to < 1 year of age

- 0.6 mg/dL for patients 1 to < 2 years of age

- 0.8 mg/dL for patients 2 to < 6 years of age

- 1 mg/dL for patients 6 to < 10 years of age

- 1.2 mg/dL for patients 10 to < 13 years of age

- 1.5 mg/dL (male) or 1.4 mg/dL (female) for patients 13 to < 16 years of age

- 1.7 mg/dL (male) or 1.4 mg/dL (female) for patients ≥ 16 years of age

- Total bilirubin ≤ 1.5 times upper limit of normal (ULN) for age

- ALT < 3.0 times ULN for age (unless elevation due to leukemia involvement)

- Shortening fraction ≥ 27% by ECHO OR LVEF ≥ 50% by gated radionuclide

- Normal respiratory rate and pulse oximetry > 94% on room air

- FEV_1 ≥ 80% of predicted

- FVC and DLCO > 50% (corrected for hemoglobin)

- Patients who are unable to perform pulmonary function tests (PFTs) (e.g.,
because of young age) will be excluded provided they have a medical history of
significant prior pulmonary events or chronic pulmonary disease (e.g.,
pneumonia requiring mechanical ventilation support, pulmonary GVHD,
pneumonectomy, or pulmonary toxin exposure)

- Children with histories of resolved bronchiolitis, resolved viral pneumonias and
well-controlled asthma are eligible, even if they are unable to perform PFTs

- Patients with seizure disorder may be enrolled if on a non-enzyme-inducing
anticonvulsant and if seizures are well-controlled

- No uncontrolled infection

- No known allergy to idarubicin, cytarabine, etoposide, boron, mannitol or bortezomib

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- Concurrent radiotherapy allowed for patients who present with a chloroma that is
producing or threatens to produce an irreversible neurologic deficit

- Recovered from all prior chemotherapy, immunotherapy, or radiotherapy

- More than 2 weeks since prior cytotoxic chemotherapy (4 weeks for nitrosoureas),
except for hydroxyurea, which is allowed up to 24 hours prior to first dose of study
drug, and intrathecal chemotherapy, which is allowed immediately up to administration
of study drug

- Prior steroid allowed as clinically indicated for patients with asthma

- Hydrocortisone and methylprednisolone allowed aspremedication in patients with a
history of severe allergic reactions

- At least 7 days since prior biologic agents, such as steroids, retinoids, or donor
lymphocyte infusion without conditioning

- At least 2 weeks since prior local palliative radiotherapy (small port)

- At least 8 weeks since prior craniospinal radiotherapy or ≥ 50% radiation of pelvis

- At least 6 weeks since prior other bone marrow radiation

- At least 1 day since prior green tea containingproducts, any products containing
vitamin C, flavanoids or other antioxidants (e.g., vitamins, herbalsupplements), and
foods with high vitamin C content

- No prior radiotherapy to > 25% of lung volume

- No prior total-body irradiation as part of a hematopoietic stem cell conditioning
regimen

- At least 2 months since prior stem cell transplantation

- No concurrent graft-vs-host disease prophylactic medication

- No prior bortezomib or other proteasome inhibitors

- No other concurrent investigational drugs

- More than 4 days since prior growth factors that support platelet or white cell
number or function

- No concurrent enzyme-inducing anticonvulsant medications known to be potent inducers
of the cytochrome P450system, including phenytoin, carbamazepine, and phenobarbital

- Concurrent benzodiazepines and gabapentin allowed

- No concurrent grapefruit juice with bortezomib

- No other concurrent cancer chemotherapy or immunomodulating agents

- No concurrent corticosteroids as anti-emetic therapy

- Concurrent corticosteroids therapy allowed as treatment or prophylaxis for
anaphylactic reactions, symptoms of cytarabine syndrome, and as treatment for
presumptive bortezomib-induced pulmonary toxicity