AZD6244 (Selumetinib) in Treating Patients With Multiple Myeloma
Condition: Recurrent Plasma Cell Myeloma; Refractory Plasma Cell Myeloma
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell
Intervention: Laboratory Biomarker Analysis; Selumetinib
Intervention description: Correlative studies; AZD6244 (Selumetinib), 75 mg was administered orally, twice a day, continuously for 28-day cycles
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 37.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase II trial studies how well selumetinib works in treating patients with multiple
      myeloma, a type of cancer in which a specific protein is over active. Selumetinib may stop
      the growth of cancer cells by blocking this protein.
    

Eligibility criteria:

        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 =< 2

          -  Absolute neutrophil count: >= 1,000/μL (independent of blood cell growth factors)

          -  Platelets: >= 75,000/μL (independent of blood cell growth factors or transfusion)

          -  Total bilirubin: =< 1.5 x upper normal limit; however, patients with documented
             Gilbert's syndrome are eligible

          -  Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase
             [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]):
             < 2.5 x upper limit of normal (ULN)

          -  Creatinine: < 3.0 x ULN

          -  Known human immunodeficiency virus (HIV) infected patients meeting the following
             characteristics are eligible:

               -  Cluster of differentiation (CD)4 cell count >= 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) =< 45% by echocardiogram (ECHO) or
             multigated acquisition scan (MUGA) scan

          -  Any requirement for supplemental oxygen