Simvastatin in Overcoming Chemotherapy Resistance in Patients With Relapsed or Refractory Multiple Myeloma

Inclusion Criteria:

* Patients must have a definitive diagnosis of multiple myeloma (using the International Myeloma Working Group Guidelines)
* Patients must meet one of the following two requirements:

  * Have achieved minimal response (MR) or stable disease (SD) in current treatment regimen after receiving a minimum of two cycles
  * Have a partial response but show a decrease less than 25% or an increase less than 25% in measurable disease over a two month period

    * NOTE: Patients may be refractory to primary therapy or relapsed and have measurable or assessable disease; (refractory disease is defined as anything less than partial response \[PR\] or progression within 60 days of completing therapy)
* Patients with multiple myeloma must have measurable disease; measurable disease may be paraprotein in serum or urine or the presence of free light chains in serum or urine defined by one or more of the following criteria:

  * Presence of serum M-protein concentration \> 1 g/dL
  * Urine M-protein excretion \> 200 mg in 24-hour urine collection
  * Serum free light chain concentration \>= 10 mg/dL and abnormal kappa/lambda ratio
  * Urine free light chain concentration \>= 100 mg/L and abnormal kappa/lambda ratio
* If female patient with reproductive capacity: on effective means of barrier birth control during the entire duration of the treatment
* Eastern Cooperative Oncology Group (ECOG) or Karnofsky performance status of 0, 1, or 2 (Karnofsky \>= 60%)
* Life expectancy of greater than 8 weeks
* Absolute neutrophil count \>= 500/ul
* Platelets \>= 30,000/ul
* Total bilirubin \< 2 times the upper limit of normal
* Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\]), alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase \[SGPT\]) \< 3 x upper limit of normal
* Patients must have adequate renal function as defined by a creatinine clearance \>= 40 mL/min (measured or estimated by the Cockcroft-Gault formula)
* Patients must have no signs of significant rhabdomyolysis determined by creatine phosphokinase (CPK) levels with a creatine kinase (CK) \< 5 times the upper limit of normal
* Patients must have recovered from acute toxicities resulting from therapy administered prior to entering this study to grade 1 or less (Common Terminology Criteria for Adverse Events \[CTCAE\] 4); alopecia may be unresolved
* Ability to understand and the willingness to sign an Institutional Review Board (IRB)-approved informed consent document

Exclusion Criteria:

* Patients who have not received any chemotherapy treatment for multiple myeloma prior to being enrolled in the study
* Patients who have no measureable disease by serologic or urine markers (detectable disease only by bone marrow or imaging scans)
* Patients who show progressive disease or are not tolerating the current chemotherapy regimen
* Patients who were receiving simvastatin (dose \> 40 mg/day) while receiving current chemotherapy regimen for multiple myeloma
* Patients receiving any other investigational agent(s)
* Active second malignancy in the last 3 years except for non-melanoma skin cancer or carcinoma-in-situ
* History of hypersensitivity reactions attributed to simvastatin
* Patients receiving medications that may increase risk of rhabdomyolysis such as itraconazole, ketoconazole, erythromycin, cyclosporine, amiodarone, verapamil, clarithromycin, nefazodone, ranolazine, human immunodeficiency virus (HIV) protease inhibitors, gemfibrozil, posaconazole, danazol, amiodarone, diltiazem, and amlodipine
* Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, myopathy, untreated hypothyroidism, hereditary myopathy in the family history, unstable angina pectoris, liver disease not due to multiple myeloma, cardiac arrhythmia that is symptomatic or not rate controlled, active connective tissue disease, active autoimmune disease, or psychiatric illness/social situations that would limit compliance with study requirements
* Pregnant women are ineligible, as treatment involves unforeseeable risks to the embryo or fetus; female patients with reproductive capacity are required to use effective means of birth control during the entire duration of the treatment
* Patients who have been on a statin other than simvastatin within 2 weeks of starting treatment on current study; these include atorvastatin, fluvastatin, lovastatin, pitavastatin, pravastatin, and rosuvastatin; if patient is on statin, will need to stop treatment 2 weeks prior to starting treatment on study