Overcoming Chemotherapy Resistance In Refractory Multiple Myeloma With Simvastatin and Zoledronic Acid

NCT01772719 | Terminated Results DMC

• 1 other identifier: BCC-HEM-11-003
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to examine the effect of simvastatin and zoledronic acid on M-protein and/or free light chains when added to conventional chemotherapy for the treatment of multiple myeloma patients.

Conditions

Multiple Myeloma

Keywords

refractory multiple myeloma

Outcome Measures

Primary Outcomes (1)

• Change in Paraprotein Level and Free Light Chain (FLC) Ratio From Baseline Measurement

  The effect of simvastatin and zolendronic acid on M-Protein and FLC ratio will be measured 4 weeks after treatment begins, then every 4 weeks until progression of disease.

  4 weeks after treatment begins

Secondary Outcomes (7)

• Overall Survival

  At start of year 2 of follow-up on all surviving participants

• Duration of Response

  Year 1 follow up visits occur monthly

• Progression Free Survival (PFS)

  At start of year 2 follow up on all surviving participants

• Duration of Response

  Year 2 follow up visit occur every three months

• Duration of Response

  Year 3-5 follow up visit occurs every six months

Study Arms (1)

Study Arm

EXPERIMENTAL

Study Arm

Drug: Simvastatin and zoledronic acid

Interventions

Simvastatin and zoledronic acid DRUG

1. Simvastatin 80 mg PO daily starting two days before starting chemotherapy and stopping two days after chemotherapy. 2. Zoledronic acid 4 mg IV over 15 minutes on day 1 and then monthly.

Also known as: Zocor

Study Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• have a definitive diagnosis of Multiple Myeloma (using the International Myeloma Working Group Guidelines).
• meet one of the following two requirements:
• Have achieved minimal response (MR) or stable disease (SD) in current treatment regimen after a minimum of two cycles.
• Have partial response but show no further improvement in paraprotein levels in the latest two measurements.
• must have measurable active or symptomatic disease. Measurable disease may be paraprotein or free light chains in serum or urine, or the presence of bone marrow plasma cells, defined by one or more of the following criteria:
• Presence of serum M-protein concentration \> 1g/dL.
• Urine M-protein excretion \> 200mg in 24-hour urine collection.
• Serum free light chain concentration ≥ 10mg/dL and abnormal kappa/lambda ratio.
• Urine free light chain concentration ≥ 100mg/L and abnormal kappa/lambda ratio.
• Bone marrow plasma cell percentage ≥ 30% (if no detectable M-protein or FLC.)
• Age \> 18 years of age.
• If female 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 (CTCAE 4) Alopecia may not be resolved.
• Ability to understand and willingness to sign a written informed consent document.
• Life expectancy of greater than 8 weeks.

You may not qualify if:

• have not received any chemotherapy treatment for multiple myeloma prior to being enrolled in the study.
• show progressive disease or are not tolerating current chemotherapy regimen.
• were receiving simvastatin (dose \> 40mg/day) while receiving current chemotherapy regimen for multiple myeloma.
• failed or progressed on more than two chemotherapy regimens, including current treatment; prior to enrolling in this study.
• receiving any other investigational agent(s).
• Active second malignancy in the last 5 years except for non-melanoma skin cancer or carcinoma-in-situ.
• 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.
• History of hypersensitivity reactions attributed to simvastatin or zoledronic acid.
• receiving medications that may increase risk of rhabdomyolysis such as itraconazole, ketoconazole, erythromycin, cyclosporine, amiodarone, verapamil, clarithromycin, nefazodone, ranolazine, 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.

Sponsors & Collaborators

• University of Louisville: lead
• James Graham Brown Cancer Center: collaborator

Study Sites (1)

James Graham Brown Cancer Center

Louisville, Kentucky, 40202, United States

Location

MeSH Terms

Conditions

Multiple Myeloma

Interventions

Simvastatin; Zoledronic Acid

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Lovastatin; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Diphosphonates; Organophosphonates; Organophosphorus Compounds; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: James Graham Brown Cancer Center, Clinical Trials
• Organization: University of Louisville, James Graham Brown Cancer Center

ctobcc@louisville.edu

502-562-3429

Study Officials

• Cesar Rodriguez, MD

  Dept. of Med Admin.

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 15, 2011
• First Posted: January 21, 2013
• Study Start: August 1, 2012
• Primary Completion: November 1, 2016
• Study Completion: November 1, 2016
• Last Updated: November 18, 2019
• Results First Posted: November 18, 2019

Record last verified: 2019-10

Locations

US (1)