AZD6244 (Selumetinib) in Treating Patients With Multiple Myeloma

Inclusion Criteria

• Confirmed diagnosis of multiple myeloma with relapsed or refractory disease following at least two prior therapies
• Measurable disease defined as:
• Serum monoclonal protein >= 1 gm/dL or
• Urine monoclonal protein of >= 200 mg/24 hours, or
• Measurable free light chains by free light chain assay of >= 10 mg/dL with abnormal kappa to lambda free light chain ratio, or
• Measurable bone disease, defined as >= 1 unidimensionally measurable lesion (longest diameter to be recorded) >= 20 mm with conventional techniques or >= 10 mm with spiral computed tomography (CT) scan (for patients with lytic bone disease)
• Eastern Cooperative Oncology Group (ECOG) performance status = = 1,000/μL (independent of blood cell growth factors)
• Platelets: >= 75,000/μL (independent of blood cell growth factors or transfusion)
• Total bilirubin: = = 500/mm^3
• Meeting either of the following:
• Willing to suspend antiretroviral therapy for duration of protocol therapy or
• On stable regimen of combination antiretroviral therapy that does not include either zidovudine or stavudine for at least 12 weeks and without evidence of toxicity
• No HIV-associated condition that defines acquired immunodeficiency syndrome (AIDS)
• Prior allogeneic stem cell transplant is allowed provided that all of the following conditions are met:
• >= 6 months have elapsed since allogeneic transplant
• No graft vs. host disease (GVHD) is present
• Not currently on immunosuppressive therapy
• Women of child-bearing potential must agree to use a medically accepted form of contraception prior to, during, and for four weeks following study treatment; men must agree to use a medically accepted form of contraception prior to, during, and for sixteen weeks following study treatment
• Able and willing to provide a written informed consent
• Prior palliative and/or localized radiation therapy is permitted, provided at least 14 days have passed from date of last radiation therapy
• Pulse oximetry of >= 95% on room air

Exclusion Criteria

• Any concurrent condition or planned treatment that would compromise study objectives or represent an unacceptable patient risk, including but not limited to:
• Planned concurrent treatment for multiple myeloma other than bisphosphonates; ongoing corticosteroids for indications other than multiple myeloma allowed as long as the dose does not exceed 60 mg of prednisone per day or equivalent
• Persisting effects of any previous or ongoing treatment that might compromise delivery of study treatment or assessment of adverse events
• Planned concurrent treatment with any other investigational agents
• Cytotoxic chemotherapy less than 2 weeks, or biologic therapy less than 2 weeks, or corticosteroids less than 2 weeks prior to registration
• No other malignancy unless the patient has been disease-free for >= 1 year
• Known multiple myeloma of central nervous system or leptomeninges
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to AZD6244
• Previous mitogen activated protein kinase (MEK) inhibitor use
• Uncontrolled hypertension, i.e., persistent blood pressure (BP) of >= 160/95
• Significant cardiovascular disease (New York Heart Association class II, III or IV cardiac disease), hypertrophic cardiomegaly or restrictive cardiomyopathy, myocardial infarction within the past 6 months, unstable angina, unstable arrhythmia unstable or a need for anti-arrhythmic therapy (use of medication for atrial fibrillation is allowed, if stable for at least 3 months)
• 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/social situations that would limit compliance with study requirements
• Pregnant or nursing
• Left ventricular ejection fraction (LVEF) =<