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Phase II Study of Simvastatin for Relapsed/Refractory Myeloma

Information source: James Graham Brown Cancer Center
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Myeloma

Intervention: Simvastatin,Zoledronic Acid,Bortezomib,Bendamustine,Methylprednisolone. (Drug)

Phase: Phase 2

Status: Withdrawn

Sponsored by: James Graham Brown Cancer Center

Official(s) and/or principal investigator(s):
Geoffrey Herzig, MD, Principal Investigator, Affiliation: James Graham Brown Cancer Center- University of Louisville


The purpose of this study test the hypothesis that the combination of simvastatin and zoledronic acid (for reversal of drug resistance), with bortezomib, high-dose methylprednisolone and bendamustine on a day 1,8 schedule (to reduce toxicity) will be an effective and well-tolerated treatment for relapsed and refractory multiple myeloma

Clinical Details

Official title: Phase II Study of Simvastatin, Zoledronic Acid, Bortezomib, Bendamustine and Methylprednisolone for Relapsed/Refractory Myeloma

Study design: Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: Response to treatment as defined by The International Myeloma Working Group response criteria for multiple myeloma.

Secondary outcome:

Progression Free Survival (PFS)

Incidence Rate of Toxicity

Overall Survival (OS)

Detailed description: OBJECTIVES Primary To estimate the overall response rate (ORR) (complete response (CR) + very good partial response (VGPR) + partial response (PR)) of patients with multiple myeloma who have relapsed or are refractory after bortezomib treatment and will now receive a combination therapy of simvastatin, zoledronic acid, bortezomib, bendamustine and methylprednisolone. To evaluate safety and tolerability of studied therapy. Secondary 1. To estimate the progression-free Survival (PFS), time to progression (TTP), overall survival (OS) and duration of response (DOR). 2. To describe toxicities (frequency and severity) during the treatment. 3 To estimate clinical benefit response (CBR) (ORR + minor response (MR)) and stable disease (SD). 4 Explore factors associated with ORR, PFS, OS, toxicity.


Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.


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


- 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.

Locations and Contacts

Additional Information

Starting date: April 2011
Last updated: April 5, 2013

Page last updated: August 23, 2015

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