Phase II Study of Simvastatin for Relapsed/Refractory Myeloma

Inclusion Criteria:

* Patients must have a diagnosis of Multiple Myeloma (using the International Myeloma Working Group Guidelines)
* Patients must have failed at least one prior treatment regimen containing bortezomib.

They may be refractory to primary therapy or relapsed and have measurable or assessable disease. (Refractory disease is defined as anything less than PR or progression within 60 days of completing therapy.)

* Patients with Multiple Myeloma must have measurable active, progressive or symptomatic disease. Measurable disease may be paraprotein or free light chains in serum or urine, or the presence of bone marrow plasma cells.
* Age- must be at least 18 years of age.
* Prior therapies may include bendamustine, bortezomib, methylprednisolone, radiation, and autologous hematopoietic cell transplant.
* Patients who have received therapy must be at least 4 weeks beyond prior chemotherapy (excluding corticosteroids).
* If female patient with reproductive capacity: on effective means of birth control during the entire duration of the treatment.
* Patients must have recovered from acute toxicities resulting from therapy administered prior to entering this study to grade 1 or less. Alopecia may not be resolved.
* Ability to understand and willingness to sign a written informed consent document.
* Life expectancy of greater than 8 weeks.
* ECOG performance status 0, 1, or 2 (Karnofsky \> 60%; see Appendix A).
* Patients must have adequate bone marrow function as defined below:

absolute neutrophil count \> 500/ul platelets \> 30,000/ul

-Patients must have adequate liver function as defined below: total bilirubin \< 2 times the upper limit of normal AST(SGOT), ALT(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 CPK levels with a CK \< 5 times the upper limit of normal.

Exclusion Criteria:

* Patients who have not received any chemotherapy treatment for multiple myeloma prior to being enrolled in the study.
* Patients who were receiving simvastatin (dose \> 40 mg/day), or the equivalent dose of another statin) during last prior chemotherapy for multiple myeloma.
* Patients who have had chemotherapy or radiotherapy within 4 weeks prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier.
* Patients receiving any other investigational agent(s).
* Active second malignancy in the last 5 years except for non-melanoma skin cancer or carcinoma-in-situ.
* History of hypersensitivity reactions attributed to simvastatin, bortezomib, bendamustine or zoledronic acid.
* Pregnant women are ineligible, as treatment involves unforeseeable risks to the embryo or fetus.
* Patients receiving medications that may increase risk of rhabdomyolysis such as itraconazole, ketoconazole, erythromycin, cyclosporine, amiodarone, verapamil, niacin, HIV protease inhibitors.
* 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.