Multiple Myeloma Stage IPhase 3NCT00171925
Therapy With Zoledronic Acid in Patients With Multiple Myeloma Stage I
A Phase 3 study testing Zoledronic acid and Calcium / Vitamin D in people with Multiple Myeloma Stage I, run by Novartis Pharmaceuticals at 1 site in Germany.
Trial summary
Multiple myeloma is a disease of B-lymphocytes producing malignant plasma cells. Malignant plasma cells induce osteolytic lesions, which is characteristic for progression of multiple myeloma. It is the aim of this study to investigate whether zoledronic acid has an influence on the progression of multiple myeloma. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Multiple Myeloma Stage I
- What is being tested?
- Zoledronic acid and Calcium / Vitamin D
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 143 participants
- Where
- 1 siteGermany
- Study dates
- Aug 2000to Nov 2008
- Phase
- Phase 3
- 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
- Evidence of myeloma according to the criteria of the British Columbia Cancer Agency (for the diagnosis, 2 of the 3 criteria must be met):
- Evidence of paraprotein in the serum or urine
- Bone marrow infiltration with plasma cells which represent more than 10% of the nucleated cells
- Radiologically, at least one osteolytic lesion
- Asymptomatic patients with Stage I (Durie and Salmon) multiple myeloma
Who cannot join
- Patients with more than one osteolytic lesion on conventional skeletal radiography
- Previous treatment with bisphosphonates
- bilirubin > 2.5 mg/dl
- Abnormal renal function as evidenced by: A calculated creatinine clearance < 30 ml/minute. Creatinine clearance (CrCl) is calculated using the Cockcroft-Gault formula:
- CrCl= [140-age(years)] x weight(kg)/[72xserumcreatinine(mg/dL)] X {0.85 for female patients}
- Patients with other malignant diseases or severe concomitant diseases
Show all 12Show fewer
- Potentially fertile patients who are not using a reliable and appropriate method of contraception
- Pregnancy or breast-feeding
- Participation in another clinical study with an investigational drug within 12 weeks of study entry
- Current active dental problems including infection of the teeth or jawbone (maxilla or mandibular); dental or fixture trauma, or a current or prior diagnosis of osteonecrosis of the jaw (ONJ), of exposed bone in the mouth, or of slow healing after dental procedures.
- Recent (within 6 weeks) or planned dental or jaw surgery (e.g.. extraction, implants)
- Other protocol-defined inclusion and exclusion criteria may apply.
Trial locations and contacts
1 site in 1 country.
About this study
Multiple myeloma is a disease of B-lymphocytes producing malignant plasma cells. Malignant plasma cells induce osteolytic lesions, which is characteristic for progression of multiple myeloma. It is the aim of this study to investigate whether zoledronic acid has an influence on the progression of multiple myeloma.
- Conditions
- Multiple Myeloma Stage I
- Being tested
- Zoledronic acid, Calcium / Vitamin D
- Keywords
- Multiple Myeloma, Stage I, Zoledronic acid, Progression
- Medical subject headings
- Multiple Myeloma, Disease Progression
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Zoledronic acidDrug
Zoledronic acid administered via normal saline intravenous infusion (over 15 minutes) every 4 weeks. Dosage was according to calculated creatinine clearance: patients with baseline creatinine clearance > 60 ml/min received 4 mg; for patients with mild to moderate renal impairment, doses were calculated to achieve the same AUC as that achieved in patients with creatinine clearance of 75 ml/min, assuming target AUC of 0.66 (mg*hr/l).
Calcium / Vitamin DDietary supplement
Patients on zoledronic acid received 500 mg calcium and 400-500 IU vitamin D combination tablet daily.
| Study group | Role | What they receive |
|---|---|---|
| Zoledronic acid (ZOL446) | Experimental | Participants received intravenous infusion of Zoledronic acid every 4 weeks for 48 weeks, and calcium and Vitamin D daily. Receives: Drug: Zoledronic acid; Dietary Supplement: Calcium / Vitamin D |
| Control | No intervention | No treatment with study medication. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Days of Progression Free Survival
Progression-free survival was defined as time from date of randomization to death from any cause or one of the following events:
- progression to stage II or III according to Salmon \& Durie classification
- skeletal related events (pathologic fracture, initiation of radiotherapy or surgery on bone, spinal cord compression or hypercalcemia)
- unequivocal progression of osteolytic lesions (at least a 20% increase in the largest diameter of one existing osteolytic lesion which is measured in at least one dimension as 20 mm with conventional techniques), determined radiologically.
Measured: 48 months
Secondary outcomes (2)
Number of Patients With Progression by Individual Criteria
Number of patients with progression by individual criteria consisting of Progression of disease overall, Skeletal-related events (including pathological fracture, initiation of radiotherapy or surgery on bone, spinal cord compression or Hypercalcemia), Progression to stage II or III according to Salmon \& Durie classification, and unequivocal progression of osteolytic lesion. Patients are counted separately for every type of progression, but only once for Overall Progression.
Measured: 48 months
The Number of Participants With the Development of Skeletal Complications
- Pathologic fracture: bone fractures that occur spontaneously or from trivial trauma. New vertebral compression fracture defined as a decrease in vertebral height of 25% from baseline
- Spinal cord compression: the impingement of tumor on the spinal cord confirmed by radiography
- Bone Radiotherapy: Bone irradiation to palliate painful lesions, treat or prevent pathologic fractures or spinal cord compression
- Surgery on bone: surgical procedures performed to set, stabilize or prevent pathologic fractures or areas of spinal cord compression
- Hypercalcemia: Corrected serum calcium ≥ 12.0 mg/dl
Measured: 48 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Sep 2005 (estimated)
- Study startAug 2000
- Primary completionNov 2008
- Study completionNov 2008
Why it stopped: Recruitment in study could not be reached after 8 yrs of recruiting
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 Myeloma Stage IStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 143 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00171925
- Sponsor's protocol ID
- CZOL446 DE01
- Status last verified
- Apr 2012
- First submitted
- 13 Sep 2005
- Last updated
- 11 Apr 2012
- Results posted
- Yes, on ClinicalTrials.gov
Study at a glance
From the registry record, last updated by the sponsor on 11 Apr 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Therapy With Zoledronic Acid in Patients With Multiple Myeloma Stage I
- ClinicalTrials.gov ID
- NCT00171925
- Acronym / sponsor ID
- CZOL446 DE01
- Conditions
- Multiple Myeloma Stage I
- Keywords
- Multiple Myeloma, Stage I, Zoledronic acid, Progression
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Recruitment in study could not be reached after 8 yrs of recruiting
- Enrolment
- 143 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- Aug 2000
- Primary completion
- Nov 2008 (actual)
- Study completion
- Nov 2008 (actual)
- First posted
- 15 Sep 2005 (estimated)
- Results
- Posted 20 Apr 2011
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Multiple myeloma is a disease of B-lymphocytes producing malignant plasma cells. Malignant plasma cells induce osteolytic lesions, which is characteristic for progression of multiple myeloma. It is the aim of this study to investigate whether zoledronic acid has an influence on the progression of multiple myeloma.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Zoledronic acid (ZOL446) | Experimental | Drug: Zoledronic acid, Dietary Supplement: Calcium / Vitamin DParticipants received intravenous infusion of Zoledronic acid every 4 weeks for 48 weeks, and calcium and Vitamin D daily. |
| Control | No intervention | –No treatment with study medication. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Evidence of myeloma according to the criteria of the British Columbia Cancer Agency (for the diagnosis, 2 of the 3 criteria must be met):
- Asymptomatic patients with Stage I (Durie and Salmon) multiple myeloma
Key exclusion criteria (12 listed)
- Patients with more than one osteolytic lesion on conventional skeletal radiography
- Previous treatment with bisphosphonates
- bilirubin > 2.5 mg/dl
- Abnormal renal function as evidenced by: A calculated creatinine clearance < 30 ml/minute. Creatinine clearance (CrCl) is calculated using the Cockcroft-Gault formula:
- Patients with other malignant diseases or severe concomitant diseases
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 |
|---|---|---|
| Zoledronic acidZoledronic acid administered via normal saline intravenous infusion (over 15 minutes) every 4 weeks. Dosage was according to calculated creatinine clearance: patients with baseline creatinine clearance > 60 ml/min received 4 mg; for patients with mild to moderate renal impairment, doses were calculated to achieve the same AUC as that achieved in patients with creatinine clearance of 75 ml/min, assuming target AUC of 0.66 (mg*hr/l). | Drug | Zoledronic acid (ZOL446) |
| Calcium / Vitamin DPatients on zoledronic acid received 500 mg calcium and 400-500 IU vitamin D combination tablet daily. | Dietary supplement | Zoledronic acid (ZOL446) |
Primary outcome
Days of Progression Free Survival
Time frame: 48 months
Progression-free survival was defined as time from date of randomization to death from any cause or one of the following events: * progression to stage II or III according to Salmon \& Durie classification * skeletal related events (pathologic fracture, initiation of radiotherapy or surgery on bone, spinal cord compression or hypercalcemia) * unequivocal progression of osteolytic lesions (at least a 20% increase in the largest diameter of one existing osteolytic lesion which is measured in at least one dimension as 20 mm with conventional techniques), determined radiologically.
2 secondary outcomes
Number of Patients With Progression by Individual Criteria
Time frame: 48 months
The Number of Participants With the Development of Skeletal Complications
Time frame: 48 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Apr 2012.
- 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.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Zoledronic acid and Calcium / Vitamin D in people with Multiple Myeloma Stage I, run by Novartis Pharmaceuticals at 1 site in Germany.
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 5 inclusion and 12 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 11 Apr 2012. 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 Germany. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 20 Apr 2011). 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?
Days of Progression Free Survival (time frame: 48 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 11 Apr 2012.