Multiple MyelomaPhase 2NCT00972959
Effect of Combination of Bortezomib/Dexamethasone/Zoledronic Acid on Bone Disease in Patients With Multiple Myeloma Relapsed After 1-3 Prior Lines of Therapy
A Phase 2 study testing Bortezomib, Zoledronic Acid and Dexamethasone in people with Multiple Myeloma, run by University of Athens at 3 sites in Greece.
Trial summary
The aim of this study is to evaluate the effect of bortezomib in combination with dexamethasone and zoledronic acid on bone mineral density (BMD) and skeletal related events (SREs) in Patients with Multiple Myeloma who Have Relapsed after 1-3 Prior Lines of Therapy 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?
- Bortezomib, Zoledronic Acid and Dexamethasone
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 17 participants
- Where
- 3 sitesGreece
- Study dates
- Jul 2009to May 2013
- 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
- Patients with Multiple Myeloma who Have Relapsed after 1-3 Prior Lines of Therapy
- Women > 50 years old
- Κarnofsky performance status ≥ 60 (patients with lower performance status due to myeloma bone disease can also be included)
- Measurable disease
- Platelet count >50x10(9)/L
- Neutrophil count >0.75x10(9)/L
Show all 12Show fewer
- Hemoglobin ≥7.0 g/dL (the use of recombinant human erythropoietin or red blood Hell transfusions to maintain hemoglobin levels above 7.0 g/dL is not an exclusion criterion)
- Serum ALT and AST ≤ 3-fold of upper normal limit
- Serum bilirubin ≤ 2-fold of upper normal limit
- Serum Calcium ≤ 10.5 mg/dL
- Expected survival ≥ 2 months
- Signed informed consent
Who cannot join
- Presence of another cancer
- Serious medical or psychiatric illness likely to interfere with participation in this clinical study
- Grade 2-4 peripheral neuropathy or neuropathic pain Grade 2 or higher as defined by NCI CTCAE version 3
- Pregnant women > 50 years old or breast-feeding
- Woman > 50 years old capable of becoming pregnant [anyone who has not undergone a hysterectomy, has not had both ovaries removed or has not been post-menopausal for more than 24 months in a row not using adequate contraception
- Known or suspected hypersensitivity or intolerance to bortezomib, boron, mannitol, zoledronic acid, dexamethasone, or heparin (if an indwelling catheter is used)
Show all 14Show fewer
- Uncontrolled diabetes (if receiving antidiabetic agents, subjects must be on a stable dose for at least 3 months prior to first dose of study drug)
- Uncontrolled or severe cardiovascular disease including myocardial infarction within 6 months of enrolment, New York Heart Association (NYHA) Class III or IV heart failure (Attachment 4, NYHA Classification of Cardiac Disease), uncontrolled angina, pericardial disease, or cardiac amyloidosis
- Acute diffuse infiltrative pulmonary disease
- History of hypotension or patient has decreased blood pressure (sitting systolic blood pressure [SBP] 100 mmHg and/or sitting diastolic blood pressure [DBP] 60 mmHg)
- Patient has received extensive radiation therapy, systemic chemotherapy, or other antineoplastic therapy within 4 weeks prior to enrolment
- Patient has received any drugs or agents that inhibit (e.g., cimetidine, erythromycin, fluoxetine, ketoconazole, paroxetine) or induce (e.g., carbamazepine, glucocorticoids, phenobarbital, rifampin) CYP2C19 or CYP3A4 within 14 days before the first dose of VELCADE (proton pump inhibitors are allowed)
- Need for therapy with concomitant CYP 3A4 inhibitors (e.g., itraconazole, fluconazole, clarithromycin, erythromycin, norfloxacin, fluvoxamine, cimetidine, indinavir, ritonavir) or inducers (e.g., efavirenz, barbiturates, phenytoin, rifampin, glitazones). Proton pump inhibitors are allowed.
- Patient has received an experimental drug or has used an experimental medical device within 4 weeks prior to the planned start of treatment. Concurrent participation in non-treatment studies is allowed, provided it will not interfere with participation in this study.
Trial locations and contacts
3 sites in 1 country.
Greece3 sites
Department of Clinical Therapeutics, University of Athens School of Medicine, "Alexandra" General Hospital
Athens, 115 28
Department of Hematology & Medical Research, 251 General Air Force Hospital
Athens, 11525
Department of Hematology, "Theagenion" Cancer Center
Thessaloniki, 540 07
About this study
Official title: A Prospective, Multicenter, Non-comparative, Open-label, Phase II Study to Evaluate the Effects of the Combination of Bortezomib/Dexamethasone/Zoledronic Acid on Bone Mineral Density, Bone Metabolism, Radiographically-detected Osteolytic Bone Lesions, Skeletal-related Events and Bone Pain in Patients With Multiple Myeloma Who Have Relapsed After 1-3 Prior Lines of Therapy
The aim of this study is to evaluate the effect of bortezomib in combination with dexamethasone and zoledronic acid on bone mineral density (BMD) and skeletal related events (SREs) in Patients with Multiple Myeloma who Have Relapsed after 1-3 Prior Lines of Therapy
Read the detailed description
Multiple Myeloma represents a malignant proliferation of plasma cells derived from a single clone. The most common symptom in myeloma, affecting more than 70% of patients at diagnosis, is bone pain. The pain usually involves the back and ribs, and is precipitated by movement. Bone fractures are commonly seen in myeloma patients and may present with persistent localized pain.
VELCADE (bortezomib) is a proteasome inhibitor used for the treatment of multiple myeloma.
VELCADE seems to be the first agent to combine significant anti-myeloma activity and beneficial effects on bone remodeling. Thus, it appears to be a very promising tool for the treatment of myeloma patients.
In this study, a regimen consisting of bortezomib/dexamethasone/zoledronic acid will be used. The rationale for using this regimen is that:
- VELCADE (bortezomib) is indicated for the treatment of relapsed myeloma patients participating in the study and it has also a beneficial effect on biochemical markers of bone formation.
- In phase II studies, the addition of dexamethasone in patients with a suboptimal response to bortezomib alone improved efficacy in relapsed or refractory multiple myeloma patients, without increasing adverse events. Therefore, in this study, the addition of dexamethasone aims at providing the optimal therapy for participating myeloma patients.
- Zoledronic acid, the most potent i.v. bisphosphonate, is used because of its established effect on reducing skeletal related events in patients with multiple myeloma due to its inhibitory effect on osteoclastic bone resorption.
Dosages and timing of dosages are based on current recommendations and guidelines for the treatment of myeloma patients who Have Relapsed after 1-3 Prior Lines of Therapy.
- Conditions
- Multiple Myeloma
- Being tested
- Bortezomib, Zoledronic Acid, Dexamethasone
- Keywords
- multiple myeloma, 1-3 Prior Lines of Therapy, bortezomib (Velcade), zoledronic acid (Zometa), Dexamethasone, bone mineral density, bone pain, bone metabolism, osteolytic lesions, DEXA-scans, X-ray radiography
- Medical subject headings
- Multiple Myeloma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BortezomibDrug
Also called Velcade
1.3 mg/m2, iv, bolus, on days 1, 4, 8 and 11 of a 21-day cycle for up to 8 chemotherapy cycles
Zoledronic AcidDrug
Also called Zometa
4 mg, iv, at a 15 min infusion, Day 1 of every cycle for up to 8 cycles, and then every 28 days for the next 18 months
DexamethasoneDrug
12 mg/m2 p.o. on days 1-2, 4-5, 8-9 and 11-12 of a 21-day cycle for up to 8 chemotherapy cycles
| Study group | Role | What they receive |
|---|---|---|
| Bortezomib/Dexamethasone/Zoledronic Acid | Experimental | For this study, Velcade will be administered at the standard dose of 1.3 mg/m2, iv, bolus, on days 1, 4, 8 and 11 of a 21-day cycle.
Dexamethasone will be administered at a dose of 12 mg/m2 p.o., on days 1-2, 4-5, 8-9 and 11-12 of the same cycle.
Zoledronic acid will be administered at a dose of 4 mg, iv (15-minute infusion), every 28 days for up to 8 cycles, and then every 28 days for the next 18 months Receives: Drug: Bortezomib; Drug: Zoledronic Acid; Drug: Dexamethasone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Bone Mineral Density (BMD)
BMD of the lumbar spine (L1-L4, anteroposterior view) and femoral neck (FN) was measured by dual energy X-ray absorptiometry (DXA) using a Hologic QDR-1000 scanner on day 21 of cycle 4 (day 84)
Measured: day 84
Secondary outcomes (11)
Bone Mineral Density (BMD)
BMD of the lumbar spine (L1-L4, anteroposterior view) and femoral neck (FN) was measured by Dual Energy X-Absorptiometry scan (DEXA-scan) using a Hologic QDR-1000 scanner on day 21 of cycle 8 (day 168)
Measured: day 168
Bone Remodelling
Bone remodelling was studied by the measurement of the following serum indices on day 21 of cycle 4 (day 84) using an enzyme-linked immunosorbent assay (ELISA): i) bone resorption marker C-terminal cross-linking telopeptide of collagen type I (CTX) and ii) bone formation markers [osteocalcin (OC)].
Measured: day 84
Bone Remodelling
Bone remodelling was studied by the measurement of the following serum indices on day 21 of cycle 8 (day 168) using an enzyme-linked immunosorbent assay (ELISA): i) bone resorption marker C-terminal cross-linking telopeptide of collagen type I (CTX) and ii) bone formation marker [osteocalcin (OC)].
Measured: day 168
Bone Pain
Bone pain was measured with the use of the Visual Analogue Scale on day 21 of cycle 4 (day 84).
Bone pain was measured with the use of the Visual Analogue Scale. The visual analogue scale or visual analog scale (VAS) is a psychometric response scale which can be used in questionnaires. It is a measurement instrument for subjective characteristics or attitudes that cannot be directly measured.
The VAS for Bone Pain was constructed as follows:
None Mild Moderate Severe Worst possible 1,2 3,4 5,6 7,8 9,10 Lower values are considered to be of a better outcome, higher values are considered to be of a worst outcome.
Measured: On the day 84
Bone Pain
Bone pain was measured with the use of the Visual Analogue Scale on day 21 of cycle 8 (day 168).
Bone pain was measured with the use of the Visual Analogue Scale. The visual analogue scale or visual analog scale (VAS) is a psychometric response scale which can be used in questionnaires. It is a measurement instrument for subjective characteristics or attitudes that cannot be directly measured.
The VAS for Bone Pain was constructed as follows:
None Mild Moderate Severe Worst possible 1,2 3,4 5,6 7,8 9,10 Lower values are considered to be of a better outcome, higher values are considered to be of a worst outcome.
Measured: On the day 168
Skeletal Survey for New Osteolytic Lesions/Fractures
Skeletal survey was measured using conventional radiography [imaging of the whole skeleton (skull, cervical spine, thoracic spine, lumbar spine, pelvis, humeri, femoral bones)] on day 21 of cycle 8 (day 168)
Measured: day 168
Skeletal Survey for New Osteolytic Lesions/Fractures
Skeletal survey was measured using conventional radiography [imaging of the whole skeleton (skull, cervical spine, thoracic spine, lumbar spine, pelvis, humeri, femoral bones)] every 6 months for up to 18 months
Measured: 18 months
New Skeletal-related Events (SRE: Pathologic Fractures, Need for Bone Radiation Therapy or Surgery)
New Skeletal-related events (SRE: pathologic fractures, need for bone radiation therapy or surgery) following 8 cycles (day 168) of therapy
Measured: day 168
New Skeletal-related Events (SRE: Pathologic Fractures, Need for Bone Radiation Therapy or Surgery)
New Skeletal-related Events (SRE: Pathologic Fractures, Need for Bone Radiation Therapy or Surgery) after 18 months post VD
Measured: 18 months
Bone Remodelling
Bone remodelling was studied by the measurement of the following serum indices on day 21 of cycle 4 (day 84) using an enzyme-linked immunosorbent assay (ELISA) bone formation marker [bone-specific alkaline phosphatase (bALP)].
Measured: day 84
Bone Remodelling
Bone remodelling was studied by the measurement of the following serum indices on day 21 of cycle 4 (day 84) using an enzyme-linked immunosorbent assay (ELISA): bone formation marker [bone-specific alkaline phosphatase (bALP) ].
Measured: day 168
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Sep 2009 (estimated)
- Study startJul 2009
- Primary completionMay 2013
- Study completionMay 2013
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
- 17 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Athens
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Meletios A. Dimopoulos, University of Athens
- Investigators
- Meletios- Athanasios Dimopoulos, Professor, Study chair, Therapeutic Clinic Department, Faculty of Medicine. University of Athens
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00972959
- Sponsor's protocol ID
- 26866138MMY 2051
- Status last verified
- Jul 2014
- First submitted
- 8 Sep 2009
- Last updated
- 5 Aug 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Aug 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Prospective, Multicenter, Non-comparative, Open-label, Phase II Study to Evaluate the Effects of the Combination of Bortezomib/Dexamethasone/Zoledronic Acid on Bone Mineral Density, Bone Metabolism, Radiographically-detected Osteolytic Bone Lesions, Skeletal-related Events and Bone Pain in Patients With Multiple Myeloma Who Have Relapsed After 1-3 Prior Lines of Therapy
- ClinicalTrials.gov ID
- NCT00972959
- Acronym / sponsor ID
- 26866138MMY 2051
- Conditions
- Multiple Myeloma
- Keywords
- multiple myeloma, 1-3 Prior Lines of Therapy, bortezomib (Velcade), zoledronic acid (Zometa), Dexamethasone, bone mineral density, bone pain, bone metabolism
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 17 participants (actual)
- Lead sponsor
- University of AthensUniversity, hospital or other
- Study start
- Jul 2009
- Primary completion
- May 2013 (actual)
- Study completion
- May 2013 (actual)
- First posted
- 9 Sep 2009 (estimated)
- Results
- Posted 5 Aug 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The aim of this study is to evaluate the effect of bortezomib in combination with dexamethasone and zoledronic acid on bone mineral density (BMD) and skeletal related events (SREs) in Patients with Multiple Myeloma who Have Relapsed after 1-3 Prior Lines of Therapy
Detailed description
Multiple Myeloma represents a malignant proliferation of plasma cells derived from a single clone. The most common symptom in myeloma, affecting more than 70% of patients at diagnosis, is bone pain. The pain usually involves the back and ribs, and is precipitated by movement. Bone fractures are commonly seen in myeloma patients and may present with persistent localized pain.
VELCADE (bortezomib) is a proteasome inhibitor used for the treatment of multiple myeloma.
VELCADE seems to be the first agent to combine significant anti-myeloma activity and beneficial effects on bone remodeling. Thus, it appears to be a very promising tool for the treatment of myeloma patients.
In this study, a regimen consisting of bortezomib/dexamethasone/zoledronic acid will be used. The rationale for using this regimen is that:
- VELCADE (bortezomib) is indicated for the treatment of relapsed myeloma patients participating in the study and it has also a beneficial effect on biochemical markers of bone formation.
- In phase II studies, the addition of dexamethasone in patients with a suboptimal response to bortezomib alone improved efficacy in relapsed or refractory multiple myeloma patients, without increasing adverse events. Therefore, in this study, the addition of dexamethasone aims at providing the optimal therapy for participating myeloma patients.
- Zoledronic acid, the most potent i.v. bisphosphonate, is used because of its established effect on reducing skeletal related events in patients with multiple myeloma due to its inhibitory effect on osteoclastic bone resorption.
Dosages and timing of dosages are based on current recommendations and guidelines for the treatment of myeloma patients who Have Relapsed after 1-3 Prior Lines of Therapy.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Bortezomib/Dexamethasone/Zoledronic Acid | Experimental | Drug: Bortezomib, Drug: Zoledronic Acid, Drug: DexamethasoneFor this study, Velcade will be administered at the standard dose of 1.3 mg/m2, iv, bolus, on days 1, 4, 8 and 11 of a 21-day cycle. Dexamethasone will be administered at a dose of 12 mg/m2 p.o., on days 1-2, 4-5, 8-9 and 11-12 of the same cycle. Zoledronic acid will be administered at a dose of 4 mg, iv (15-minute infusion), every 28 days for up to 8 cycles, and then every 28 days for the next 18 months |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Patients with Multiple Myeloma who Have Relapsed after 1-3 Prior Lines of Therapy
- Women > 50 years old
- Κarnofsky performance status ≥ 60 (patients with lower performance status due to myeloma bone disease can also be included)
- Measurable disease
- Platelet count >50x10(9)/L
Key exclusion criteria (14 listed)
- Presence of another cancer
- Serious medical or psychiatric illness likely to interfere with participation in this clinical study
- Grade 2-4 peripheral neuropathy or neuropathic pain Grade 2 or higher as defined by NCI CTCAE version 3
- Pregnant women > 50 years old or breast-feeding
- Woman > 50 years old capable of becoming pregnant [anyone who has not undergone a hysterectomy, has not had both ovaries removed or has not been post-menopausal for more than 24 months in a row not using adequate contraception
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 |
|---|---|---|
| BortezomibAlso: Velcade1.3 mg/m2, iv, bolus, on days 1, 4, 8 and 11 of a 21-day cycle for up to 8 chemotherapy cycles | Drug | Bortezomib/Dexamethasone/Zoledronic Acid |
| Zoledronic AcidAlso: Zometa4 mg, iv, at a 15 min infusion, Day 1 of every cycle for up to 8 cycles, and then every 28 days for the next 18 months | Drug | Bortezomib/Dexamethasone/Zoledronic Acid |
| Dexamethasone12 mg/m2 p.o. on days 1-2, 4-5, 8-9 and 11-12 of a 21-day cycle for up to 8 chemotherapy cycles | Drug | Bortezomib/Dexamethasone/Zoledronic Acid |
Primary outcome
Bone Mineral Density (BMD)
Time frame: day 84
BMD of the lumbar spine (L1-L4, anteroposterior view) and femoral neck (FN) was measured by dual energy X-ray absorptiometry (DXA) using a Hologic QDR-1000 scanner on day 21 of cycle 4 (day 84)
11 secondary outcomes
Bone Mineral Density (BMD)
Time frame: day 168
Bone Remodelling
Time frame: day 84
Bone Remodelling
Time frame: day 168
Bone Pain
Time frame: On the day 84
Bone Pain
Time frame: On the day 168
Skeletal Survey for New Osteolytic Lesions/Fractures
Time frame: day 168
Skeletal Survey for New Osteolytic Lesions/Fractures
Time frame: 18 months
New Skeletal-related Events (SRE: Pathologic Fractures, Need for Bone Radiation Therapy or Surgery)
Time frame: day 168
New Skeletal-related Events (SRE: Pathologic Fractures, Need for Bone Radiation Therapy or Surgery)
Time frame: 18 months
Bone Remodelling
Time frame: day 84
Bone Remodelling
Time frame: day 168
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Aug 2014.
- 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.
Meletios- Athanasios Dimopoulos, Professor study chair
Therapeutic Clinic Department, Faculty of Medicine. University of Athens
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Bortezomib, Zoledronic Acid and Dexamethasone in people with Multiple Myeloma, run by University of Athens at 3 sites in Greece.
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 12 inclusion and 14 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: finished, as of the sponsor's last update on 5 Aug 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Greece. 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 5 Aug 2014). 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?
Bone Mineral Density (BMD) (time frame: day 84). 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 5 Aug 2014.