Selumetinib in Treating Patients With Recurrent or Refractory Acute Myeloid Leukemia

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