MyelomaPhase 2NCT01332617
Phase II Study of Simvastatin for Relapsed/Refractory Myeloma
A Phase 2 study testing Simvastatin,Zoledronic Acid,Bortezomib,Bendamustine,Methylprednisolone. in people with Myeloma, run by University of Louisville.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Myeloma
- What is being tested?
- Simvastatin,Zoledronic Acid,Bortezomib,Bendamustine,Methylprednisolone.
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- Apr 2011to Feb 2019
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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
- 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.
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- 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.
Who cannot join
- 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.
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- 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.
About this study
Official title: Phase II Study of Simvastatin, Zoledronic Acid, Bortezomib, Bendamustine and Methylprednisolone for Relapsed/Refractory Myeloma
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
Read the 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
- To estimate the progression-free Survival (PFS), time to progression (TTP), overall survival (OS) and duration of response (DOR).
- 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.
- Conditions
- Myeloma
- Being tested
- Simvastatin,Zoledronic Acid,Bortezomib,Bendamustine,Methylprednisolone.
- Keywords
- Multiple Myeloma, Simvastatin, Zoledronic, Bortezomib, Bendamustine, Methylprednisolone
- Medical subject headings
- Neoplasms, Plasma Cell, Multiple Myeloma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Simvastatin,Zoledronic Acid,Bortezomib,Bendamustine,Methylprednisolone.Drug
Also called Simvastatin (ZOCOR), Methylprednisolone (Medrol), Bortezomib (Voltarol, Diclofenac), Bendamustine (Treanda)
- Simvastatin 80 mg PO daily starting day -2 through day 10.
- Zoledronic acid 4 mg IV over 15 minutes on day 1 and then monthly
- Bortezomib 1.3 mg/m2/day IV bolus on days 3,6 and 10.
- Bendamustine 100 mg/m2/day IV over 30 minute infusion on days 3 and 10.
- Methylprednisolone 1g/m2 IV over 30 minutes on days 1 and 8.
| Study group | Role | What they receive |
|---|---|---|
| Treatment with combination therapy | Experimental | Treatment with combination therapy of Simvastatin, Zoledronic Acid, Bortezomib, Bendamustine, and Methylprednisolone. Receives: Drug: Simvastatin,Zoledronic Acid,Bortezomib,Bendamustine,Methylprednisolone. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Response to treatment as defined by The International Myeloma Working Group response criteria for multiple myeloma.
Response catergories (IMWG):
Complete Remission(CR), Very Good Partial Remission(VGPR), Partial Remission (PR), Minor Response (MR), Progressive Disease (PD), Stable Disease, Relapse,Refractory Disease, Overall Response.
Measured: 4 weeks after first dose of simvastatin
Secondary outcomes (3)
Progression Free Survival (PFS)
PFS is measured from date of study enrollment until the date of progressive disease is documented.
Measured: After 1 year of follow-up.
Incidence Rate of Toxicity
Decriptive statistics will be provided regarding incidence rates of toxcity. Patients will be monitored for safety throughout the study.
Measured: End of study; monitoring during study.
Overall Survival (OS)
OS is measured from date of study enrollment until death.
Measured: After 1 year of follow-up
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Apr 2011 (estimated)
- Study startApr 2011
- Primary completionFeb 2018 (estimated)
- Study completionFeb 2019 (estimated)
Why it stopped: Investigators no longer interested in activating study
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 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
- Geoffrey Herzig, MD, Principal investigator, James Graham Brown Cancer Center- University of Louisville
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01332617
- Sponsor's protocol ID
- BCC-HEM-10-001
- Status last verified
- Dec 2017
- First submitted
- 7 Apr 2011
- Last updated
- 29 Dec 2017
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 29 Dec 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Study of Simvastatin, Zoledronic Acid, Bortezomib, Bendamustine and Methylprednisolone for Relapsed/Refractory Myeloma
- ClinicalTrials.gov ID
- NCT01332617
- Acronym / sponsor ID
- BCC-HEM-10-001
- Conditions
- Myeloma
- Keywords
- Multiple Myeloma, Simvastatin, Zoledronic, Bortezomib, Bendamustine, Methylprednisolone
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Investigators no longer interested in activating study
- Enrolment
- 0 participants (actual)
- Lead sponsor
- University of LouisvilleUniversity, hospital or other
- Collaborators
- James Graham Brown Cancer Center
- Study start
- Apr 2011
- Primary completion
- Feb 2018 (estimated)
- Study completion
- Feb 2019 (estimated)
- First posted
- 11 Apr 2011 (estimated)
- Results
- Not posted in the source record
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 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
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
- To estimate the progression-free Survival (PFS), time to progression (TTP), overall survival (OS) and duration of response (DOR).
- 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment with combination therapy | Experimental | Drug: Simvastatin,Zoledronic Acid,Bortezomib,Bendamustine,Methylprednisolone.Treatment with combination therapy of Simvastatin, Zoledronic Acid, Bortezomib, Bendamustine, and Methylprednisolone. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- 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.
Key exclusion criteria (9 listed)
- 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.
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,Zoledronic Acid,Bortezomib,Bendamustine,Methylprednisolone.Also: Simvastatin (ZOCOR), Methylprednisolone (Medrol), Bortezomib (Voltarol, Diclofenac), Bendamustine (Treanda)1. Simvastatin 80 mg PO daily starting day -2 through day 10. 2. Zoledronic acid 4 mg IV over 15 minutes on day 1 and then monthly 3. Bortezomib 1.3 mg/m2/day IV bolus on days 3,6 and 10. 4. Bendamustine 100 mg/m2/day IV over 30 minute infusion on days 3 and 10. 5. Methylprednisolone 1g/m2 IV over 30 minutes on days 1 and 8. | Drug | Treatment with combination therapy |
Primary outcome
Response to treatment as defined by The International Myeloma Working Group response criteria for multiple myeloma.
Time frame: 4 weeks after first dose of simvastatin
Response catergories (IMWG): Complete Remission(CR), Very Good Partial Remission(VGPR), Partial Remission (PR), Minor Response (MR), Progressive Disease (PD), Stable Disease, Relapse,Refractory Disease, Overall Response.
3 secondary outcomes
Progression Free Survival (PFS)
Time frame: After 1 year of follow-up.
Incidence Rate of Toxicity
Time frame: End of study; monitoring during study.
Overall Survival (OS)
Time frame: After 1 year of follow-up
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Dec 2017.
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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.
Geoffrey Herzig, MD principal investigator
James Graham Brown Cancer Center- University of Louisville
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Simvastatin,Zoledronic Acid,Bortezomib,Bendamustine,Methylprednisolone. in people with Myeloma, run by University of Louisville.
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 17 inclusion and 9 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: withdrawn, as of the sponsor's last update on 29 Dec 2017. Status can change between updates, so confirm with the study contact before making plans.
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.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
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?
Response to treatment as defined by The International Myeloma Working Group response criteria for multiple myeloma. (time frame: 4 weeks after first dose of simvastatin). 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 29 Dec 2017.