Phase I Study of Decitabine (Dacogen) and Bortezomib (Velcade) in Acute Myeloid Leukemia

Inclusion Criteria:

- Diagnosis of acute myeloid leukemia (AML), meeting one of the following criteria:

- Relapsed or refractory disease (≥ 18 years of age)

- Previously untreated disease (≥ 60 years of age)

- Secondary AML or therapy-related AML allowed

- No granulocytic sarcoma as the sole site of disease

- No active or relapsed CNS disease

- No advanced malignant solid tumors

- ECOG performance status 0-2

- Life expectancy > 6 months (if patient has co-morbid illness)

- Total bilirubin < 2.0 mg/dL

- AST and ALT < 2.5 times upper limit of normal

- Creatinine < 2.0 mg/dL

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- Patients with HIV infection are eligible provided the following criteria are met:

- No history of AIDS

- Has a sufficiently high CD4 count (> 400/mm³)

- Has low HIV viral loads (< 30,000 copies/mL plasma)

- Does not require anti-HIV therapy

- No uncontrolled active infection

- No history of allergic reactions attributed to compounds of similar chemical or
biological composition to decitabine or bortezomib that are not easily managed

- No hypersensitivity to boron or mannitol

- No concurrent uncontrolled illness including, but not limited to, any of the
following:

- Symptomatic congestive heart failure

- Unstable or uncontrolled angina pectoris

- Serious cardiac arrhythmia

- Myocardial infarction within the past 6 months

- New York Heart Association class III-IV heart failure

- Severe uncontrolled ventricular arrhythmias

- Acute ischemia or active conduction system abnormalities by ECG

- No serious medical or psychiatric illness or social situation that would preclude
participation in this study

- No pre-existing neuropathy ≥ grade 2

- No other serious neurologic toxicity that would significantly increase the risk of
complications from bortezomib therapy

- Recovered from prior therapy (toxicity < grade 2)

- More than 14 days since prior investigational agents

- More than 2 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin C)
or radiotherapy

- Prior decitabine or azacitidine for myelodysplastic syndromes (MDS) or AML allowed

- More than 6 months since prior decitabine, azacitidine, or bortezomib

- No concurrent palliative radiotherapy

- No other concurrent investigational agents

- No other concurrent direct anti-leukemia therapy