Multiple MyelomaPhase 2NCT01965834
Phase II Study to Evaluate Fenofibrate Therapy in Patients With Smoldering or Symptomatic Multiple Myeloma
A Phase 2 study testing Fenofibrate in people with Multiple Myeloma, run by University of Miami at 1 site in United States.
Trial summary
Multiple myeloma cells are dependent on calcium (Ca2+) for their function. Specifically, Ca2+ is required for the function of the endoplasmic reticulum in which proteins, including immunoglobulins, are folded prior to their release from the cell. 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?
- Fenofibrate
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 6 participants
- Where
- 1 siteUnited States
- Study dates
- 19 Nov 2012to 1 Jul 2016
- Phase
- Phase 2
- 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
- Patient must have histologically or cytologically confirmed multiple myeloma (smoldering myeloma and symptomatic multiple myeloma).
- Patients must have measurable disease and therefore must have at least one of the following:
- Serum M-protein ≥ 1 gm/dL (≥ 10 gm/L)
- Urine M-protein ≥ 200 mg/24 hr
- Serum free light chain (FLC) assay: involved FLC ≥ 10 mg/dL (≥ 100 mg/L) provided serum FLC ratio is abnormal.
- Male or female ≥ 18 years of age.
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- Life expectancy of ≥ 6 months.
- Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
- Normal organ and marrow function as defined below:
- Absolute Neutrophil Count (ANC) ≥ 1,000/mm^3
- Platelets ≥75,000/mm^3
- Hemoglobin ≥ 8 g/dL
- Calculated serum creatinine (calculated by Cockcroft-Gault method) ≥ 30 mL/min
- Aspartate transaminase (AST)/serum glutamic oxaloacetic transaminase (SGOT)/ Alanine transaminase (ALT)/serum glutamate-pyruvate transaminase (SGPT) ≤ 2.5 X upper limit of normal (ULN)
- Total bilirubin ≤ 1.5 X ULN
- Patient must be at least 2 weeks from prior chemotherapy, radiation therapy, biological therapy, immunotherapy, major surgery and any other investigational anti-cancer therapy prior to the first dose of study drug.
- Patient has recovered from toxicities (≤ Grade 2) and/or complications from prior therapy.
- Patient is able to swallow capsules and is able to take or tolerate oral medications on a continuous basis.
- Female patients of childbearing potential must be willing to use 2 adequate barrier methods of contraception to prevent pregnancy or agrees to abstain from heterosexual intercourse for at least 1 month before dosing, and while women are on study and for up to 12 weeks after last dose of study drug. Adequate contraceptive methods include intrauterine device, diaphragm with spermicide, cervical cap with spermicide, or female condom with spermicide. Spermicides alone are not an acceptable method of contraception.
- Male patients agree to have female partners of childbearing potential use 2 adequate barrier methods of contraception as described in Section 3.1.10.
- Female patients of childbearing potential must have a negative serum pregnancy test within 7 days prior to the first dose of study drug.
- Patient is available for periodic blood sampling, study related assessments and management at the treating institution for the duration of the study.
- Ability to understand and the willingness to sign a written informed consent document.
Who cannot join
- Patients who only present with isolated plasmacytomas
- Inability to swallow oral medication.
- Prior allogeneic stem cell transplant (subject with prior autologous transplant is eligible).
- Patient has plans to undergo any type of stem cell transplantation (allogeneic or autologous) within 4 weeks of initiation of study therapy.
- Concurrent therapy with 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMG-CoA) Reductase Inhibitors.
- Patient with gallbladder disease or cholelithiasis.
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- Patient has active liver disease, including biliary cirrhosis and unexplained liver function abnormalities.
- Patients receiving renal dialysis.
- History of hypersensitivity to fenofibrate or fenofibric acid, including sever skin rashes (e.g., Stevens-Johnson syndrome, toxic epidermal necrolysis)
- Patients who would be receiving any other investigational agents while on study.
- Participation in any investigational drug study within 4 weeks preceding the start of study treatment.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- Patient has systemic infection requiring treatment.
- Patient has acute diffuse infiltrative pulmonary disease or pericardial disease.
- Subject is receiving corticosteroid therapy (> 10 mg of prednisone or equivalent).
- Subject is a regular user or has a recent history (within the last year) of any illicit drugs, or substance abuse.
- Subject is pregnant or breast feeding, or expecting to conceive or father children within the projected duration of the study.
- Subject is known to be HIV positive.
- Subject has clinically active Hepatitis B or C
- History of prior malignancy except for cervical carcinoma in situ, non-melanoma skin cancer, adequately treated localized prostate cancer with prostate-specific antigen (PSA) < 0.1, or has undergone potentially curative therapy with no evidence of disease for five years, or who is deemed at low risk for recurrence by his/her treating physician.
- Patient with central nervous system (CNS) metastases and/or carcinomatous meningitis.
- History of gastrointestinal disease that could potentially impact the ability of the patient to swallow and/or absorb study drug (i.e., gastrointestinal surgery, malabsorption syndrome, subjects requiring the use of feeding tube)
- History of gastrointestinal surgery or other procedures that might in the opinion of the investigator interfere with swallowing and/or absorption of the study drug.
Trial locations and contacts
1 site in 1 country.
About this study
Multiple myeloma cells are dependent on calcium (Ca2+) for their function. Specifically, Ca2+ is required for the function of the endoplasmic reticulum in which proteins, including immunoglobulins, are folded prior to their release from the cell. Multiple myeloma cells secrete large concentrations of immunoglobulins continuously and as result depend on mitochondria activity to replenish the Ca2+ levels in the endoplasmic reticulum as was shown in vitro in our lab. Fenofibrate has been shown to inhibit mitochondrial function resulting in inhibition of protein folding in the endoplasmic reticulum of multiple myeloma (MM) cells that leads to the induction of a stress signal known as the unfolded protein response and subsequently apoptosis. The effective anti-myeloma concentrations for fenofibrate are attainable in the clinical setting as they are in the same range as the effective concentrations for anti-hyperlipidemic effect. The investigators propose to evaluate fenofibrate therapy in multiple myeloma patients.
- Conditions
- Multiple Myeloma
- Being tested
- Fenofibrate
- Keywords
- Multiple Myeloma, Fenofibrate
- Medical subject headings
- Multiple Myeloma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FenofibrateDrug
Also called Fenofibric acid
Upon screening, registration and enrollment, all subjects will receive Fenofibrate 160 mg orally daily for at least 2 months and may continue receiving study medication for as long as in the opinion of the investigator there is clinical benefit in doing so. Patients with calculated creatinine clearance < 50 mL/min will receive a reduced dose of 54 mg orally daily.
| Study group | Role | What they receive |
|---|---|---|
| Fenofibrate Therapy | Experimental | Fenofibrate orally daily for each 28 day cycle, per study protocol. Receives: Drug: Fenofibrate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Rate of Response in Participants Receiving Fenofibrate Therapy
To determine response rate (Strict Complete Response (sCR), Complete response (CR), Very Good Partial Response (VgPR), and Partial Response (PR)) in multiple myeloma patients receiving oral fenofibrate therapy. Response will be measured by serum and urine protein electrophoresis and immunofixation, as well as by percentage of plasma cells present on bone marrow biopsy.
Measured: After two cycles, about 2 months
Secondary outcomes (2)
Number of Subjects Experiencing Adverse Events
To evaluate safety and tolerability of fenofibrate therapy in patients with multiple myeloma.
Measured: Up to 8 months
Proportion of Participants Achieving Progression-Free Survival
Proportion of participants achieving progression-free survival. Measured from date of initiation of treatment (Day 1) to the earliest occurrence of any of the following events: documented disease progression, or death from any cause. Patients who are alive and progression-free will be censored at the date of last documented progression-free status.
Measured: 6 months, 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Oct 2013 (estimated)
- Study start19 Nov 2012
- Primary completion21 Mar 2016
- Study completion1 Jul 2016
Why it stopped: Lack of adequate accrual.
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.
- 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
- 6 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Miami
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Denise Pereira, University of Miami
- Investigators
- Denise Pereria, MD, Principal investigator, University of Miami
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01965834
- Sponsor's protocol ID
- 20110069
- Status last verified
- May 2017
- First submitted
- 15 Oct 2013
- Last updated
- 14 Jun 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 Jun 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Study to Evaluate Fenofibrate Therapy in Patients With Smoldering or Symptomatic Multiple Myeloma
- ClinicalTrials.gov ID
- NCT01965834
- Acronym / sponsor ID
- 20110069
- Conditions
- Multiple Myeloma
- Keywords
- Multiple Myeloma, Fenofibrate
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Lack of adequate accrual.
- Enrolment
- 6 participants (actual)
- Lead sponsor
- University of MiamiUniversity, hospital or other
- Study start
- 19 Nov 2012 (actual)
- Primary completion
- 21 Mar 2016 (actual)
- Study completion
- 1 Jul 2016 (actual)
- First posted
- 18 Oct 2013 (estimated)
- Results
- Posted 14 Jun 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Multiple myeloma cells are dependent on calcium (Ca2+) for their function. Specifically, Ca2+ is required for the function of the endoplasmic reticulum in which proteins, including immunoglobulins, are folded prior to their release from the cell. Multiple myeloma cells secrete large concentrations of immunoglobulins continuously and as result depend on mitochondria activity to replenish the Ca2+ levels in the endoplasmic reticulum as was shown in vitro in our lab. Fenofibrate has been shown to inhibit mitochondrial function resulting in inhibition of protein folding in the endoplasmic reticulum of multiple myeloma (MM) cells that leads to the induction of a stress signal known as the unfolded protein response and subsequently apoptosis. The effective anti-myeloma concentrations for fenofibrate are attainable in the clinical setting as they are in the same range as the effective concentrations for anti-hyperlipidemic effect. The investigators propose to evaluate fenofibrate therapy in multiple myeloma patients.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Fenofibrate Therapy | Experimental | Drug: FenofibrateFenofibrate orally daily for each 28 day cycle, per study protocol. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (23 listed)
- Patient must have histologically or cytologically confirmed multiple myeloma (smoldering myeloma and symptomatic multiple myeloma).
- Patients must have measurable disease and therefore must have at least one of the following:
- Male or female ≥ 18 years of age.
- Life expectancy of ≥ 6 months.
- Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
Key exclusion criteria (23 listed)
- Patients who only present with isolated plasmacytomas
- Inability to swallow oral medication.
- Prior allogeneic stem cell transplant (subject with prior autologous transplant is eligible).
- Patient has plans to undergo any type of stem cell transplantation (allogeneic or autologous) within 4 weeks of initiation of study therapy.
- Concurrent therapy with 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMG-CoA) Reductase Inhibitors.
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 |
|---|---|---|
| FenofibrateAlso: Fenofibric acidUpon screening, registration and enrollment, all subjects will receive Fenofibrate 160 mg orally daily for at least 2 months and may continue receiving study medication for as long as in the opinion of the investigator there is clinical benefit in doing so. Patients with calculated creatinine clearance < 50 mL/min will receive a reduced dose of 54 mg orally daily. | Drug | Fenofibrate Therapy |
Primary outcome
Rate of Response in Participants Receiving Fenofibrate Therapy
Time frame: After two cycles, about 2 months
To determine response rate (Strict Complete Response (sCR), Complete response (CR), Very Good Partial Response (VgPR), and Partial Response (PR)) in multiple myeloma patients receiving oral fenofibrate therapy. Response will be measured by serum and urine protein electrophoresis and immunofixation, as well as by percentage of plasma cells present on bone marrow biopsy.
2 secondary outcomes
Number of Subjects Experiencing Adverse Events
Time frame: Up to 8 months
Proportion of Participants Achieving Progression-Free Survival
Time frame: 6 months, 12 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Jun 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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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.
Denise Pereria, MD principal investigator
University of Miami
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Fenofibrate in people with Multiple Myeloma, run by University of Miami 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 23 inclusion and 23 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 14 Jun 2017. 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.
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?
Yes. Results are posted in the registry (first posted 14 Jun 2017). 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?
Rate of Response in Participants Receiving Fenofibrate Therapy (time frame: After two cycles, about 2 months). 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 14 Jun 2017.