Selumetinib and Azacitidine in High Risk Chronic Blood Cancers

Eligibility Criteria

• * Age greater than or equal to 18 years of age
• * Histologic confirmation of one of the following:
• * No history of prior exposure to a MEK inhibitor
• * ECOG performance status of ≤ 2
• * Adequate renal function, defined as serum creatinine ≤ 1.5 x ULN or creatinine clearance \>30 mL/min based on the Cockroft-Gault equation: (140 - Age) x (weight in kg) x (0.85 if female) / 72 x serum creatinine
• * Adequate liver function, defined as conjugated bilirubin ≤ 2 x ULN as well as aspartate transaminase (AST) and alanine aminotransaminase (ALT) ≤ 3 x ULN
• * Patients must be at least 2 weeks from major surgery, radiation therapy, participation in other investigational trials and must have recovered from clinically significant toxicities of these prior treatments
• * Female patients of childbearing potential must have a negative serum pregnancy test within 2 weeks prior to enrollment
• * Female and male patients must use an effective contraceptive method during the study and for at least 6 months thereafter
• * Ability to understand and willingness to sign a written informed consent document
• * Receipt of any anti-cancer therapy within 14 days prior to study entry, with the exception of hydroxyurea. If clinically indicated in order to keep WBC \<30,000/uL, hydroxyurea may be continued through the first cycle.
• * Concurrent active malignancy, with the exception of early stage basal cell or squamous cell skin cancer
• * Active cardiac conditions, including any of the following:
• 1. Uncontrolled hypertension (BP \>150/95 mmHg despite medical therapy)
• 2. Acute coronary syndrome within 6 months prior to starting treatment
• 3. Uncontrolled angina despite medical therapy
• 4. Symptomatic heart failure (NYHA class II-IV despite medical therapy)
• 5. Baseline LV EF \<50% measured by either echocardiography or MUGA scan
• 6. Severe valvular heart disease
• 7. Atrial fibrillation with ventricular rate \>100 bpm on EKG at rest.
• * Ophthalmologic conditions, including any of the following:
• 1. Current or past history of central serous retinopathy
• 2. Current or past history of retinal vein occlusion
• 3. Intraocular pressure (IOP) \>21 mmHg or uncontrolled glaucoma
• * Any uncontrolled concurrent illness that, in the judgment of the investigators or treating physician, may put the patient at undo risk including but not limited to active infection, symptomatic cardiac or pulmonary disease, ventricular arrhythmia, or psychiatric illness.
• * Pregnant or lactating patients