Azacytidine and Bortezomib in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia or Myelodysplastic Syndromes

Inclusion criteria:

* Patients must be \>18 with relapsed or refractory acute myeloid leukemia (AML) and high risk (by IPSS scoring) Myelodysplastic Syndromes (MDS)
* Patients with secondary AML or therapy related disease (t-AML) are eligible If decitabine or Vidaza was a prior treatment for MDS or AML patient is eligible.Prior Velcade is also permitted.
* ECOG performance status 0-2
* Life expectancy \> 6 months for patients with a co-morbid medical illness
* Total bilirubin \< 2.0mg/dL
* AST/ALT \< 2.5 times upper limit of normal (ULN)
* Creatinine \< 2.0 mg/dL
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception prior to and during study treatment
* Ability to understand and willingness to sign the written informed consent document
* Active infection is allowed provided it is under control

Exclusion criteria:

* History of allergic reactions attributed to compounds of similar chemical or biologic composition to azacytidine or bortezomib that are not easily managed
* Hypersensitivity to bortezomib, boron, or mannitol
* Uncontrolled intercurrent illness including, but not limited to:

  * Symptomatic congestive heart failure
  * Unstable angina pectoris
  * Serious cardiac arrhythmia
  * Psychiatric illness/social situations that would limit compliance with study
* Myocardial infarction within 6 months prior to enrollment
* New York Heart Association (NYHA) Class III or IV congestive heart failure
* Uncontrolled angina
* Severe uncontrolled ventricular arrhythmia
* Electrocardiographic evidence of acute ischemia
* Active conduction system abnormalities
* ECG abnormality that is medically relevant
* Psychiatric conditions that prevent compliance with protocol or consent.
* Pre-existing neuropathy grade 2 or higher or other serious neurologic toxicity that would significantly increase risk of complications from bevacizumab therapy
* Serious medical or psychiatric illness likely to interfere with participation in this clinical study
* Diagnosis or treatment for another malignancy within 3 years of enrollment, with the exception of any of the following:

  * Complete resected basal cell carcinoma
  * Squamous cell carcinoma of the skin
  * Any in situ malignancy
  * Low-risk prostate cancer after curative therapy

PRIOR CONCURRENT THERAPY:

* Prior decitabine or azacytidine for MDS or AML is allowed
* Prior bortezomib allowed
* More than 2 weeks since prior chemotherapy or radiotherapy (6 weeks for nitrosoureas or mitomycin C)
* More than 14 days since prior and no concurrent investigational agents
* No concurrent combination antiretroviral therapy for HIV-positive patients