CancerPhase 2NCT00983346
Effect of Low Dose Bortezomib on Bone Formation in Smoldering Myeloma Patients
A Phase 2 study testing Bortezomib in people with Cancer and Myeloma, run by University of Utah at 1 site in United States.
Trial summary
OBJECTIVES Primary: To evaluate the bone anabolic effect of bortezomib in patients with smoldering myeloma. Secondary: To evaluate the effect of bortezomib on the natural history of smoldering myeloma. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cancer, Myeloma, Multiple Myeloma
- What is being tested?
- Bortezomib
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 17 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2009to Sep 2014
- 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 diagnosis of smoldering multiple myeloma
- Male or Female patients aged ≥ 18 years old
- Ability to provide written informed consent (obtained prior to participation in the study and any related procedures being performed) with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.
- Female subject is either post-menopausal or surgically sterilized or willing to use an acceptable method of birth control (i.e., a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of the study
- Male subject agrees to use an acceptable method for contraception for the duration of the study.
- Serum M protein ≥3 g/dL and/or
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- Bone marrow plasma cells ≥10%
- Absence of anemia, renal failure, hypercalcemia, and lytic bone lesions
- ANC ≥ 1.5 x 109 /L
- Hemoglobin ≥ 10g/dl
- Platelets ≥ 100 x 109 /L
- AST and ALT ≤2.5 x ULN
- Serum bilirubin ≤2.0 x ULN
Who cannot join
- Platelet count of <100 109/L within 14 days before enrollment.
- Absolute neutrophil count of <1.0 109/L within 14 days before enrollment.
- Creatinine clearance of <30 mL/minute within 14 days before enrollment.
- Patient has Grade 2 peripheral neuropathy within 14 days before enrollment.
- Myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) Class III or IV heart failure (see section 8.4), uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Prior to study entry, any ECG abnormality at Screening has to be documented by the investigator as not medically relevant.
- Patient has hypersensitivity to bortezomib, boron or mannitol.
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- Female subject is pregnant or breast-feeding. Confirmation that the subject is not pregnant must be established by a negative serum human chorionic gonadotropin (hCG) pregnancy test result obtained during screening. Pregnancy testing is not required for post-menopausal or surgically sterilized women.
- Patient has received other investigational drugs with 14 days before enrollment
- Serious medical or psychiatric illness likely to interfere with participation in this clinical study.
- Diagnosed or treated for another malignancy within 3 years of enrollment, with the exception of complete resection of basal cell carcinoma or squamous cell carcinoma of the skin, an in situ malignancy, or low-risk prostate cancer after curative therapy.
- Patients currently taking bisphosphonates
Trial locations and contacts
1 site in 1 country.
United States1 site
Huntsman Cancer Institute
Salt Lake City, Utah, 84112
About this study
OBJECTIVES
- Primary: To evaluate the bone anabolic effect of bortezomib in patients with smoldering myeloma.
- Secondary: To evaluate the effect of bortezomib on the natural history of smoldering myeloma.
Read the detailed description
Smoldering multiple myeloma (SMM) is usually followed expectantly without therapy. The overall risk of progression to active multiple myeloma has been estimated up to 20% in the first year from diagnosis (Kyle et al, 2007). An angiogenic switch has been postulated as a pivotal event in the progression from MGUS to smoldering myeloma. Two trials for advanced and refractory MM patients tested this hypothesis using Thalidomide as antiangiogenic agent in association with biphosphonates showing and effect on disease progression (Barlogie et al, 2008).
The ubiquitin-proteasome pathway, which has been shown to be an essential cellular degradative system in myeloma cells, also regulates bone formation though effects on osteoblast differentiation (Pennisi et al., 2008).
Retrospective analysis of ALP variation in 2 large Bortezomib trials in the refractory setting confirmed the finding. In the SUMMIT trial (Zangari, et al., 2005), 77 patients were evaluated. The media increment ALP in levels of responding patients (patients with >50% decrease in paraprotein) upon completion of 3 cycles of therapy was statistically higher of those individuals with less than partial response (week 8, P=0.0015; responder range, 62-837 mL/L). In the APEX trial (Zangari et al. 2005), 422 patients were analyzed; 217 patients were randomized to bortezomib, 205 to dexamethasone. Within the bortezomib arm, the increment in serum ALP levels in responder patients (>CR) was statistically higher at week 3 (P=0.014), week 6 (P=0.002; responder rage, 31-272 mL/L) and week 9 (P=0.036). Comparing only responders patients in both arms of the study, we observed a significantly higher median ALP increase in the bortezomib compared to the dexamethasone arm (P<0.01; responder ran, 31-272 mL/L) (Zangari et al., 2007). A 25% increase in ALP (N=105) at week 6 was also the strongest indicator associated with quality of response (P<0.0001) and also with the time to progression (206 vs. 169 days) relative to patients with less than a 25% increase in ALP (N=228; P=0.01) (Zangari et al., 2007). We will now test the bone anabolic effect of bortezomib in a cohort of smoldering multiple myeloma patients.
Study rationale and selection of drug doses VELCADE has been shown to produce an anabolic bone effect (increase bone ALP and osteocalcin) in relapsed/refractory patients. This study will examine the bone anabolic effect in patients with smoldering myeloma who, with a median age of 67 years, have frequent evidence of osteopenia not associated with lytic bone disease. Risk of disease progression is estimated at 10% per year in this patient population. The primary aim of this trial is to determine the effect of a short course (i.e. 9 cycles) of low-dose Bortezomib on bone remodeling and on disease progression. The dose of bortezomib used in this trial of 0.7 mg/m2 is the lowest dose which has shown efficacy in the 3 largest monotherapy trials with bortezomib. Seventeen percent of patients in the APEX 9% of patients in CREST and 24% in SUMMIT trials were treated with 0.7 mg/m2 dosages. Bortezomib will be given on days 1, 8, 15, 22 over 42 days to reduce the incidence of possible drug related side effects.
- Conditions
- Cancer, Myeloma, Multiple Myeloma
- Being tested
- Bortezomib
- Keywords
- cancer, myeloma, multiple myeloma, smoldering myeloma
- Medical subject headings
- Neoplasms, Neoplasms, Plasma Cell, Multiple Myeloma, Smoldering 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
Bortezomib will be administered as a 3-5 second bolus IV injection at the dose of 0.7 mg/m2 on days 1, 8, 15, and 22 of each 42 day cycle.
Patients will undergo nine 42-day cycles. At the end of this (day 378), patients will be assessed for bone remodeling changes. Evaluation for toxicities will be evaluated at the beginning of each cycle.
| Study group | Role | What they receive |
|---|---|---|
| All patients | Experimental | All participants enrolled. Receives: Drug: Bortezomib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Bone Anabolic Effect of Bortezomib in Patients With Smoldering Myeloma.
The primary endpoint is the change in bone Alkaline Phosphatase at baseline and 6 weeks.
Measured: Baseline and 6 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Sep 2009 (estimated)
- Study startOct 2009
- Primary completionSep 2014
- Study completionSep 2014
Why it stopped: Lab Staff that was required left the institution, therefore accrual closed prematurely
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 CancerStudies of the same condition, open and under way.
- More trials run by University of UtahThe 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
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 17 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Utah
- Sponsor type
- University, hospital or other
- Collaborators
- Millennium Pharmaceuticals, Inc.
- Responsible party
- Sponsor
- Investigators
- Maurizio Zangari, MD, Principal investigator, University of Utah
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00983346
- Sponsor's protocol ID
- HCI33979
- Status last verified
- Jul 2016
- First submitted
- 22 Sep 2009
- Last updated
- 11 Jul 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 11 Jul 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Low Dose Bortezomib on Bone Formation in Smoldering Myeloma Patients
- ClinicalTrials.gov ID
- NCT00983346
- Acronym / sponsor ID
- HCI33979
- Conditions
- Cancer, Myeloma, Multiple Myeloma
- Keywords
- cancer, myeloma, multiple myeloma, smoldering myeloma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Lab Staff that was required left the institution, therefore accrual closed prematurely
- Enrolment
- 17 participants (actual)
- Lead sponsor
- University of UtahUniversity, hospital or other
- Collaborators
- Millennium Pharmaceuticals, Inc.
- Study start
- Oct 2009
- Primary completion
- Sep 2014 (actual)
- Study completion
- Sep 2014 (actual)
- First posted
- 24 Sep 2009 (estimated)
- Results
- Posted 30 Nov 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
OBJECTIVES
- Primary: To evaluate the bone anabolic effect of bortezomib in patients with smoldering myeloma.
- Secondary: To evaluate the effect of bortezomib on the natural history of smoldering myeloma.
Detailed description
Smoldering multiple myeloma (SMM) is usually followed expectantly without therapy. The overall risk of progression to active multiple myeloma has been estimated up to 20% in the first year from diagnosis (Kyle et al, 2007). An angiogenic switch has been postulated as a pivotal event in the progression from MGUS to smoldering myeloma. Two trials for advanced and refractory MM patients tested this hypothesis using Thalidomide as antiangiogenic agent in association with biphosphonates showing and effect on disease progression (Barlogie et al, 2008).
The ubiquitin-proteasome pathway, which has been shown to be an essential cellular degradative system in myeloma cells, also regulates bone formation though effects on osteoblast differentiation (Pennisi et al., 2008).
Retrospective analysis of ALP variation in 2 large Bortezomib trials in the refractory setting confirmed the finding. In the SUMMIT trial (Zangari, et al., 2005), 77 patients were evaluated. The media increment ALP in levels of responding patients (patients with >50% decrease in paraprotein) upon completion of 3 cycles of therapy was statistically higher of those individuals with less than partial response (week 8, P=0.0015; responder range, 62-837 mL/L). In the APEX trial (Zangari et al. 2005), 422 patients were analyzed; 217 patients were randomized to bortezomib, 205 to dexamethasone. Within the bortezomib arm, the increment in serum ALP levels in responder patients (>CR) was statistically higher at week 3 (P=0.014), week 6 (P=0.002; responder rage, 31-272 mL/L) and week 9 (P=0.036). Comparing only responders patients in both arms of the study, we observed a significantly higher median ALP increase in the bortezomib compared to the dexamethasone arm (P<0.01; responder ran, 31-272 mL/L) (Zangari et al., 2007). A 25% increase in ALP (N=105) at week 6 was also the strongest indicator associated with quality of response (P<0.0001) and also with the time to progression (206 vs. 169 days) relative to patients with less than a 25% increase in ALP (N=228; P=0.01) (Zangari et al., 2007). We will now test the bone anabolic effect of bortezomib in a cohort of smoldering multiple myeloma patients.
Study rationale and selection of drug doses VELCADE has been shown to produce an anabolic bone effect (increase bone ALP and osteocalcin) in relapsed/refractory patients. This study will examine the bone anabolic effect in patients with smoldering myeloma who, with a median age of 67 years, have frequent evidence of osteopenia not associated with lytic bone disease. Risk of disease progression is estimated at 10% per year in this patient population. The primary aim of this trial is to determine the effect of a short course (i.e. 9 cycles) of low-dose Bortezomib on bone remodeling and on disease progression. The dose of bortezomib used in this trial of 0.7 mg/m2 is the lowest dose which has shown efficacy in the 3 largest monotherapy trials with bortezomib. Seventeen percent of patients in the APEX 9% of patients in CREST and 24% in SUMMIT trials were treated with 0.7 mg/m2 dosages. Bortezomib will be given on days 1, 8, 15, 22 over 42 days to reduce the incidence of possible drug related side effects.
Study design
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| All patients | Experimental | Drug: BortezomibAll participants enrolled. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Patients with diagnosis of smoldering multiple myeloma
- Male or Female patients aged ≥ 18 years old
- Ability to provide written informed consent (obtained prior to participation in the study and any related procedures being performed) with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.
- Female subject is either post-menopausal or surgically sterilized or willing to use an acceptable method of birth control (i.e., a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of the study
- Male subject agrees to use an acceptable method for contraception for the duration of the study.
Key exclusion criteria (11 listed)
- Platelet count of <100 109/L within 14 days before enrollment.
- Absolute neutrophil count of <1.0 109/L within 14 days before enrollment.
- Creatinine clearance of <30 mL/minute within 14 days before enrollment.
- Patient has Grade 2 peripheral neuropathy within 14 days before enrollment.
- Myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) Class III or IV heart failure (see section 8.4), uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Prior to study entry, any ECG abnormality at Screening has to be documented by the investigator as not medically relevant.
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: VelcadeBortezomib will be administered as a 3-5 second bolus IV injection at the dose of 0.7 mg/m2 on days 1, 8, 15, and 22 of each 42 day cycle. Patients will undergo nine 42-day cycles. At the end of this (day 378), patients will be assessed for bone remodeling changes. Evaluation for toxicities will be evaluated at the beginning of each cycle. | Drug | All patients |
Primary outcome
Bone Anabolic Effect of Bortezomib in Patients With Smoldering Myeloma.
Time frame: Baseline and 6 weeks
The primary endpoint is the change in bone Alkaline Phosphatase at baseline and 6 weeks.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Jul 2016.
- 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.
Maurizio Zangari, MD principal investigator
University of Utah
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 Bortezomib in people with Cancer and Myeloma, run by University of Utah 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 13 inclusion and 11 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 Jul 2016. 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 30 Nov 2015). 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 Anabolic Effect of Bortezomib in Patients With Smoldering Myeloma. (time frame: Baseline and 6 weeks). 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 Jul 2016.