Multiple MyelomaNCT01772719
Overcoming Chemotherapy Resistance In Refractory Multiple Myeloma With Simvastatin and Zoledronic Acid
A study testing Simvastatin and zoledronic acid in people with Multiple Myeloma, run by University of Louisville at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Multiple Myeloma
- What is being tested?
- Simvastatin and zoledronic acid
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 7 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2012to Nov 2016
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
- ECOG performance status 0, 1, or 2 (Karnofsky > 60%; see Appendix A).
- have adequate bone marrow function as defined below:
- absolute neutrophil count > 500/ul
- platelets > 30,000/ul
- 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
- have adequate renal function as defined by a creatinine clearance > 40 mL/min (measured or estimated by the Cockcroft-Gault formula).
- have no signs of significant rhabdomyolysis determined by CPK levels with a CK < 5 times the upper limit of normal.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
James Graham Brown Cancer Center
Louisville, Kentucky, 40202
About this study
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.
Read the 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
- Conditions
- Multiple Myeloma
- Being tested
- Simvastatin and zoledronic acid
- Keywords
- refractory multiple myeloma
- Medical subject headings
- Multiple Myeloma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Simvastatin and zoledronic acidDrug
Also called Zocor
- Simvastatin 80 mg PO daily starting two days before starting chemotherapy and stopping two days after chemotherapy.
- Zoledronic acid 4 mg IV over 15 minutes on day 1 and then monthly.
| Study group | Role | What they receive |
|---|---|---|
| Study Arm | Experimental | Study Arm Receives: Drug: Simvastatin and zoledronic acid |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 4 weeks after treatment begins
Secondary outcomes (7)
Overall Survival
OS(Overall survival) is measured from date of study enrollment until death.
Measured: At start of year 2 of follow-up on all surviving participants
Duration of Response
Response will be accessed by one of the study investigators at each monthly follow up visit during year one.
Measured: Year 1 follow up visits occur monthly
Progression Free Survival (PFS)
Study will estimate PFS when there is one year of follow up data for all surviving participants
Measured: At start of year 2 follow up on all surviving participants
Duration of Response
Response will be assessed by one of the study investigators at each three month follow up visit for Year 2
Measured: Year 2 follow up visit occur every three months
Duration of Response
Response will be assessed by one of the study investigators at each six month follow up visit for Year 3-5
Measured: Year 3-5 follow up visit occurs every six months
Incidence Rate of Toxicity
Descriptive statistics will be provided regarding incidence rates of toxicity. Patients will be monitored for safety throughout the study.
Measured: Every 12 months up to one month after treatment completion
Comparison of Quality of Life Scores
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
Measured: Up to 2 months after last treatment has been completed
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jan 2013 (estimated)
- Study startAug 2012
- Primary completionNov 2016
- Study completionNov 2016
Why it stopped: Principal Investigator left institution-study not continued
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Multiple MyelomaStudies of the same condition, open and under way.
- More trials run by University of LouisvilleThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 7 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Louisville
- Sponsor type
- University, hospital or other
- Collaborators
- James Graham Brown Cancer Center
- Responsible party
- Sponsor
- Investigators
- Cesar Rodriguez, MD, Principal investigator, Dept. of Med Admin.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01772719
- Sponsor's protocol ID
- BCC-HEM-11-003
- Status last verified
- Oct 2019
- First submitted
- 15 Nov 2011
- Last updated
- 18 Nov 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 18 Nov 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Overcoming Chemotherapy Resistance In Refractory Multiple Myeloma With Simvastatin and Zoledronic Acid
- ClinicalTrials.gov ID
- NCT01772719
- Acronym / sponsor ID
- BCC-HEM-11-003
- Conditions
- Multiple Myeloma
- Keywords
- refractory multiple myeloma
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Principal Investigator left institution-study not continued
- Enrolment
- 7 participants (actual)
- Lead sponsor
- University of LouisvilleUniversity, hospital or other
- Collaborators
- James Graham Brown Cancer Center
- Study start
- Aug 2012
- Primary completion
- Nov 2016 (actual)
- Study completion
- Nov 2016 (actual)
- First posted
- 21 Jan 2013 (estimated)
- Results
- Posted 18 Nov 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Study Arm | Experimental | Drug: Simvastatin and zoledronic acidStudy Arm |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (24 listed)
- have a definitive diagnosis of Multiple Myeloma (using the International Myeloma Working Group Guidelines).
- meet one of the following two requirements:
- 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:
- Age > 18 years of age.
- If female with reproductive capacity: on effective means of birth control during the entire duration of the treatment.
Key exclusion criteria (10 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Simvastatin and zoledronic acidAlso: Zocor1. 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. | Drug | Study Arm |
Primary outcome
Change in Paraprotein Level and Free Light Chain (FLC) Ratio From Baseline Measurement
Time frame: 4 weeks after treatment begins
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.
7 secondary outcomes
Overall Survival
Time frame: At start of year 2 of follow-up on all surviving participants
Duration of Response
Time frame: Year 1 follow up visits occur monthly
Progression Free Survival (PFS)
Time frame: At start of year 2 follow up on all surviving participants
Duration of Response
Time frame: Year 2 follow up visit occur every three months
Duration of Response
Time frame: Year 3-5 follow up visit occurs every six months
Incidence Rate of Toxicity
Time frame: Every 12 months up to one month after treatment completion
Comparison of Quality of Life Scores
Time frame: Up to 2 months after last treatment has been completed
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Nov 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Cesar Rodriguez, MD principal investigator
Dept. of Med Admin.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Simvastatin and zoledronic acid in people with Multiple Myeloma, run by University of Louisville at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 24 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 18 Nov 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 18 Nov 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Paraprotein Level and Free Light Chain (FLC) Ratio From Baseline Measurement (time frame: 4 weeks after treatment begins). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Nov 2019.