Inclusion Criteria:

- Histologically or cytologically confirmed diagnosis of 1 of the following:

- Relapsed or refractory acute myeloid leukemia (AML)

- Secondary AML including AML arising from antecedent hematologic diseases (e.g.,
myelodysplastic syndrome, myeloproliferative disorders, or therapy-related AML)

- Elderly patients ≥ 60 years of age, previously untreated, and who are not candidates
for or have refused standard chemotherapy are eligible for this trial

- Patients with relapsed acute promyelocytic leukemia (APL) who are FLT3+ and have
failed both tretinoin and arsenic therapy are eligible for this trial

- No known active CNS disease

- ECOG performance status (PS) 0-2 or Karnofsky PS 60-100%

- Total bilirubin ≤ 2 mg/dL (unless due to disease, hemolysis, or Gilbert disease)

- In patients with associated hemolysis or Gilbert disease, a bilirubin of > 2
mg/dL is allowed as a result of predominantly unconjugated hyperbilirubinemia

- AST/ALT < 3 times upper limit of normal

- Creatinine < 2 mg/dL

- Baseline pulse oximetry > 92%

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception prior to, during, and for 4 weeks
(16 week for males) after completion of study treatment

- Recovered from prior therapy

- At least 2 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin C)
or radiotherapy

- Hydroxyurea may be administered for the first 7 days of therapy in patients with
rapidly rising white count (WBC > 20 K/μL)

- At least 4 weeks since prior investigational agents

- No prior MEK inhibitors

- No concurrent medication that can prolong the QT interval

- No other concurrent investigational agents

- No concurrent combination antiretroviral therapy for HIV-positive patients

Exclusion Criteria:

- History of allergic reactions attributed to compounds of similar chemical or
biological composition to AZD6244 or its excipient Captisol®

- QTc interval > 450 msecs or other factors that increase the risk of QT prolongation
or arrhythmic events (e.g., heart failure, hypokalemia, or family history of long QT
interval syndrome), including New York Heart Association class III or IV heart
failure

- Refractory nausea and vomiting, chronic gastrointestinal diseases (e.g., inflammatory
bowel disease), or significant bowel resection that would preclude adequate
absorption

- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection or psychiatric illness or social situations that would limit compliance
with study requirements