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

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by James Graham Brown Cancer Center
Sponsor:
Collaborator:
University of Louisville
Information provided by (Responsible Party):
James Graham Brown Cancer Center
ClinicalTrials.gov Identifier:
NCT01772719
First received: November 15, 2011
Last updated: May 19, 2014
Last verified: May 2014
  Purpose

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.


Condition Intervention
Multiple Myeloma
Drug: Simvastatin and zoledronic acid

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Overcoming Chemotherapy Resistance In Refractory Multiple Myeloma With Simvastatin and Zoledronic Acid

Resource links provided by NLM:


Further study details as provided by James Graham Brown Cancer Center:

Primary Outcome Measures:
  • Change in Paraprotein level and free light chain (FLC) ratio from Baseline measurement [ Time Frame: 4 weeks after treatment begins ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Overall survival [ Time Frame: At start of year 2 of follow-up on all surviving participants ] [ Designated as safety issue: Yes ]
    OS(Overall survival) is measured from date of study enrollment until death.

  • Duration of response [ Time Frame: Year 1 follow up visits occur monthly ] [ Designated as safety issue: No ]
    Response will be accessed by one of the study investigators at each monthly follow up visit during year one.

  • Progression Free Survival (PFS) [ Time Frame: At start of year 2 follow up on all surviving participants ] [ Designated as safety issue: Yes ]
    Study will estimate PFS when there is one year of follow up data for all surviving participants

  • Duration of response [ Time Frame: Year 2 follow up visit occur every three months ] [ Designated as safety issue: No ]
    Response will be assessed by one of the study investigators at each three month follow up visit for Year 2

  • Duration of response [ Time Frame: Year 3-5 follow up visit occurs every six months ] [ Designated as safety issue: No ]
    Response will be assessed by one of the study investigators at each six month follow up visit for Year 3-5

  • Incidence Rate of Toxicity [ Time Frame: Every 12 months up to one month after treatment completion ] [ Designated as safety issue: Yes ]
    Descriptive statistics will be provided regarding incidence rates of toxicity. Patients will be monitored for safety throughout the study.

  • Comparison of Quality of Life scores [ Time Frame: Up to 2 months after last treatment has been completed ] [ Designated as safety issue: No ]
    The QOL scores taken at the start of the study and every 4 months after treatment starts will be analyzed using Wilcoxon test for paired differences


Estimated Enrollment: 15
Study Start Date: August 2012
Estimated Study Completion Date: October 2014
Estimated Primary Completion Date: October 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Study Arm
Study Arm
Drug: Simvastatin and zoledronic acid
  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.
Other Name: Zocor

Detailed Description:

We hypothesize that the addition of simvastatin and zoledronic acid to bortezomib, thalidomide, melphalan or dexamethasone based regimens will decrease drug resistance when treating refractory multiple myeloma. We hypothesize that the addition of simvastatin and zoledronic acid will not increase the chemotherapy toxicity significantly and will be tolerable for patients. We believe simvastatin and zoledronic acid have antitumor properties and will contribute to reversal of resistance. Treatment will be significantly enhanced when these agents are combined

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. have a definitive diagnosis of Multiple Myeloma (using the International Myeloma Working Group Guidelines).
  2. 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.
  3. 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.)
  4. Age > 18 years of age.
  5. If female with reproductive capacity: on effective means of birth control during the entire duration of the treatment.
  6. 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.
  7. Ability to understand and willingness to sign a written informed consent document.
  8. Life expectancy of greater than 8 weeks.
  9. ECOG performance status 0, 1, or 2 (Karnofsky > 60%; see Appendix A).
  10. have adequate bone marrow function as defined below:

    • absolute neutrophil count > 500/ul
    • platelets > 30,000/ul
  11. 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
  12. have adequate renal function as defined by a creatinine clearance > 40 mL/min (measured or estimated by the Cockcroft-Gault formula).
  13. have no signs of significant rhabdomyolysis determined by CPK levels with a CK < 5 times the upper limit of normal.

Exclusion Criteria:

  1. have not received any chemotherapy treatment for multiple myeloma prior to being enrolled in the study.
  2. show progressive disease or are not tolerating current chemotherapy regimen.
  3. were receiving simvastatin (dose > 40mg/day) while receiving current chemotherapy regimen for multiple myeloma.
  4. failed or progressed on more than two chemotherapy regimens, including current treatment; prior to enrolling in this study.
  5. receiving any other investigational agent(s).
  6. Active second malignancy in the last 5 years except for non-melanoma skin cancer or carcinoma-in-situ.
  7. 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.
  8. History of hypersensitivity reactions attributed to simvastatin or zoledronic acid.
  9. 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.
  10. 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01772719

Contacts
Contact: David P Figg, BS 502-562-562-4006
Contact: Cesar Rodriguez, MD 502-562-4363

Locations
United States, Kentucky
James Graham Brown Cancer Center Recruiting
Louisville, Kentucky, United States, 40202
Contact: David P Figg    502-562-4006      
Contact: Cesar Rodriguez    502-562-4363      
Principal Investigator: Geoffrey Herzig, MD         
Sub-Investigator: Roger Herzig, MD         
Sponsors and Collaborators
James Graham Brown Cancer Center
University of Louisville
Investigators
Principal Investigator: Cesar Rodriguez, MD Dept. of Med Admin.
  More Information

No publications provided

Responsible Party: James Graham Brown Cancer Center
ClinicalTrials.gov Identifier: NCT01772719     History of Changes
Other Study ID Numbers: BCC-HEM-11-003
Study First Received: November 15, 2011
Last Updated: May 19, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by James Graham Brown Cancer Center:
refractory multiple myeloma

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Blood Protein Disorders
Cardiovascular Diseases
Hematologic Diseases
Hemorrhagic Disorders
Hemostatic Disorders
Immune System Diseases
Immunoproliferative Disorders
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Paraproteinemias
Vascular Diseases
Diphosphonates
Simvastatin
Zoledronic acid
Anticholesteremic Agents
Antimetabolites
Bone Density Conservation Agents
Enzyme Inhibitors
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Hypolipidemic Agents
Lipid Regulating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on November 25, 2014