Multiple MyelomaPhase 2NCT00464178
A Phase II Study of Bevacizumab and Bortezomib in Patients With Relapsed/Refractory Multiple Myeloma
A Phase 2 study testing Bortezomib in people with Multiple Myeloma, run by Hackensack Meridian Health at 1 site in United States.
Trial summary
The purpose of this study is to determine whether the combination of bevacizumab and bortezomib have increased efficacy in the treatment of relapsed/ refractory multiple myeloma. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Multiple Myeloma
- What is being tested?
- Bortezomib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 7 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 2007to Feb 2009
- 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
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Must have been previously diagnosed with multiple myeloma based on Durie-Salmon criteria and/or the diagnostic criteria developed by the International Myeloma Working Group (IMWG).The patient must currently require therapy for relapsed (progressive disease, defined as a 25% increase in M-protein, development of new or worsening of existing lesions or soft tissue plasmacytoma, or hypercalcemia, or relapse from CR. Or patient must have disease that is refractory to most recent therapy. Defined as less than a 50% reduction in serum paraprotein or 90% reduction in urine paraprotein.
- Must have measurable disease, defined as follows: For secretory multiple myeloma, measurable levels of monoclonal protein: greater than or equal to 0.5g/dL on electrophoresis or greater than or equal to 200mg of monoclonal light chain on a 24 hour protein electrophoresis.
- Must have had at least one prior line of therapy but no more than three prior lines of therapy.
- Must understand and voluntarily sign an informed consent form.
- Must be greater than/equal to 18 years of age at time of signing consent.
- Must be able to adhere to study visit schedule and other protocol requirements.
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- Must have an ECOG performance status of 0,1or 2
- Women of Child-bearing potential (WCBP) defined as a sexually mature woman who has not undergone a hysterectomy or who has not been naturally post-menopausal for at least 24 consecutive months must have a negative serum or urine pregnancy test within 7 days of starting study drug. In addition, sexually active WCBP must agree to use adequate contraceptive methods (oral, injectable, or implantable hormonal contraceptive method; tubal ligation; intra-uterine device; barrier contraceptive with spermicide; or vasectomized partner) while on study medication.
- All WCBP and all sexually active male patients must agree to use adequate methods of birth control throughout the study.
Who cannot join
- Inability to comply with study and/or follow-up procedures
- Life expectancy of less than 12 weeks
- Inadequately controlled hypertension (defined as systolic blood pressure >150 and/or diastolic blood pressure > 100 mmHg on antihypertensive medications)
- Any prior history of hypertensive crisis or hypertensive encephalopathy
- New York Heart Association (NYHA) Grade II or greater congestive heart failure or left ventricular ejection fraction (LVEF) < 40% (Note: baseline evaluation of LVEF should be performed for any patient who has received >450mg/m2 of any anthracycline during prior chemotherapy.
- History of myocardial infarction or unstable angina within 6 months prior to study enrollment
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- History of stroke or transient ischemic attack within 6 months prior to study enrollment
- Known CNS disease
- Significant vascular disease (e.g., aortic aneurysm, aortic dissection)
- Symptomatic peripheral vascular disease
- Known hypersensitivity to any component of bevacizumab and/or bortezomib
- Previously treated with Bortezomib and/or Bevacizumab.
- Received nitrosoureas within 3 weeks or any other chemotherapy, including thalidomide or clarithromycin, or radiation therapy before enrollment.
- Received corticosteroids (greater than 10mg/day prednisone or equivalent) within three weeks prior to enrollment.
- Received immunotherapy or antibody therapy within 8 weeks prior to enrollment.
- Received plasmapheresis within 4 weeks before enrollment.
- Had major surgery within 4 weeks before enrollment. (kyphoplasty is not considered major surgery)
- History of allergic reactions attributable to compounds containing boron or mannitol.
- Grade 3 or greater peripheral neuropathy as defined by the NCI Common Toxicity Criteria (NCI CTC version 3.0) Grade 3: Sensory loss or paresthesia interfering with ADLs. Grade 4: Permanent sensory loss that interferes with function.
Trial locations and contacts
1 site in 1 country.
United States1 site
The Cancer Center at Hackensack University Medical Center
Hackensack, New Jersey, 07601
About this study
Official title: A Phase II Study of Bevacizumab and Bortezomib in Patients With Relapsed Refractory Multiple Myeloma
The purpose of this study is to determine whether the combination of bevacizumab and bortezomib have increased efficacy in the treatment of relapsed/ refractory multiple myeloma.
Read the detailed description
Rationale: With the identification of thalidomide as an active agent in Multiple Myeloma, the role of angiogenesis in its pathogenesis has become a subject of much investigation. Micro vessel density (neovascularization) is inversely related to prognosis in Multiple Myeloma. Response to thalidomide was felt to correlate with a decline in microvessel density (Singhal et al NEJM). While the mechanism of neovascularization is yet to be fully elucidated, a number of models have shown VEGF to play a central role.
Thalidomide has been shown to synergize with a number of agents used to treat MM, including bortezomib. (Wang et al ASH 2005) This would justify the use of other therapeutics with known antiangiogenic activity in conjunction with established antimyeloma therapies.
Bortezomib, which has the precedence of known synergy with Thalidomide and has an extremely well established optimal dose, schedule, response rate, event free survival, and overall survival would make it an excellent candidate for combination therapy with other established antiangiogenic compounds.
There have been several reports of the role of VEGF in multiple myeloma. It has been shown that multiple myeloma cells secreteVEGF, which further promotes production of IL-6 in BMSCs, as well as migration and proliferation of the tumor cells. Thus VEGF is both an autocrine growth factor and trigger of IL-6-mediated paracrine multiple myeloma cell growth. Recent reports have highlighted the major role of VEGF in multiple myeloma pathogenesis, demonstrating the VEGF also increases microvessel density in the bone marrow. VEGF also inhibits dendritic cells. Taken together, these preclinical reports make strong suggestion for the promise of VEGF targeted agents in multiple myeloma (Le Gouill et al 2004).
- Conditions
- Multiple Myeloma
- Being tested
- Bortezomib
- Keywords
- multiple myeloma, myeloma, relapsed myeloma, refractory myeloma, relapsed, refractory myeloma, relapsed, refractory multiple myeloma, refractory multiple myeloma, relapsed multiple myeloma, B lymphoid malignancies, Myeloma, Plasma-Cell, Myeloma Proteins, hnRNP A1, myeloma helix-destabilizing protein, mouse, IgC3kappa Jir protein, human, gamma 3 myeloma protein Jir, human, M-proteins (Myeloma), M315 myeloma protein, mouse, myeloma protein M 315, mouse, McPC603 antibody, myeloma protein McPC603 antibody
- Medical subject headings
- Multiple Myeloma, Neoplasms, Plasma Cell, Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BortezomibDrug
Also called Bortezomib will be administered
Bortezomib will be administered at 1.3 mglm2 IVP on Days 1. 4, 8, and 11. Response will be assessed subsequent to each cycle. A total of 8 cycles would beplanned. Patients would be removed subsequent to Cycle 2. if progression of disease is documented.
| Study group | Role | What they receive |
|---|---|---|
| Bortezomib and bevacizumab | Experimental | Bortezomib will be administered at 1.3 mglm2 IVP on Days 1. 4, 8, and 11. Response will be assessed subsequent to each cycle. A total of 8 cycles would beplanned. Patients would be removed subsequent to Cycle 2. if progression of disease is documented. Receives: Drug: Bortezomib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Median Number of Cycles to Tumor Progression (TTP)
Study Schema: Bortezomib will be administered on Days 1. 4, 8, and 11. Response will be assessed subsequent to each 21-day cycle. Progression is defined using the Bladé criteria, defined progression as an increase of >25% in paraprotein or urinary light chain excretion (or marrow plasma cell percentage in the marrow
Measured: 18 months
Overall Survival (OS) - Number of Participants Alive at Study Completion
The secondary objective of this study is to assess the safely and tolerability of the combination treatment of bevacizumnab and bortezomnib. Adjustments in the dosing schedule of bortezomib would be made for patients with adequate response as per Blade criteria and continue until disease progression or 18 months
Measured: 18 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Apr 2007 (estimated)
- Study startApr 2007
- Primary completionFeb 2009
- Study completionFeb 2009
Why it stopped: The study was closed early due to poor 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
- 7 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hackensack Meridian Health
- Sponsor type
- University, hospital or other
- Collaborators
- Genentech, Inc.
- Responsible party
- Sponsor
- Investigators
- David S Siegel, MD, PhD, Principal investigator, The Cancer Center at Hackensack University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00464178
- Sponsor's protocol ID
- AV3502s
- Other IDs
- AVF3502s, 20070359
- Status last verified
- Jun 2022
- First submitted
- 19 Apr 2007
- Last updated
- 20 Jul 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 Jul 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study of Bevacizumab and Bortezomib in Patients With Relapsed Refractory Multiple Myeloma
- ClinicalTrials.gov ID
- NCT00464178
- Acronym / sponsor ID
- AV3502s
- Conditions
- Multiple Myeloma
- Keywords
- multiple myeloma, myeloma, relapsed myeloma, refractory myeloma, relapsed, refractory myeloma, relapsed, refractory multiple myeloma, refractory multiple myeloma, relapsed multiple myeloma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The study was closed early due to poor accrual
- Enrolment
- 7 participants (actual)
- Lead sponsor
- Hackensack Meridian HealthUniversity, hospital or other
- Collaborators
- Genentech, Inc.
- Study start
- Apr 2007
- Primary completion
- Feb 2009 (actual)
- Study completion
- Feb 2009 (actual)
- First posted
- 23 Apr 2007 (estimated)
- Results
- Posted 20 Jul 2022
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 is to determine whether the combination of bevacizumab and bortezomib have increased efficacy in the treatment of relapsed/ refractory multiple myeloma.
Detailed description
Rationale: With the identification of thalidomide as an active agent in Multiple Myeloma, the role of angiogenesis in its pathogenesis has become a subject of much investigation. Micro vessel density (neovascularization) is inversely related to prognosis in Multiple Myeloma. Response to thalidomide was felt to correlate with a decline in microvessel density (Singhal et al NEJM). While the mechanism of neovascularization is yet to be fully elucidated, a number of models have shown VEGF to play a central role.
Thalidomide has been shown to synergize with a number of agents used to treat MM, including bortezomib. (Wang et al ASH 2005) This would justify the use of other therapeutics with known antiangiogenic activity in conjunction with established antimyeloma therapies.
Bortezomib, which has the precedence of known synergy with Thalidomide and has an extremely well established optimal dose, schedule, response rate, event free survival, and overall survival would make it an excellent candidate for combination therapy with other established antiangiogenic compounds.
There have been several reports of the role of VEGF in multiple myeloma. It has been shown that multiple myeloma cells secreteVEGF, which further promotes production of IL-6 in BMSCs, as well as migration and proliferation of the tumor cells. Thus VEGF is both an autocrine growth factor and trigger of IL-6-mediated paracrine multiple myeloma cell growth. Recent reports have highlighted the major role of VEGF in multiple myeloma pathogenesis, demonstrating the VEGF also increases microvessel density in the bone marrow. VEGF also inhibits dendritic cells. Taken together, these preclinical reports make strong suggestion for the promise of VEGF targeted agents in multiple myeloma (Le Gouill et al 2004).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Bortezomib and bevacizumab | Experimental | Drug: BortezomibBortezomib will be administered at 1.3 mglm2 IVP on Days 1. 4, 8, and 11. Response will be assessed subsequent to each cycle. A total of 8 cycles would beplanned. Patients would be removed subsequent to Cycle 2. if progression of disease is documented. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Must have been previously diagnosed with multiple myeloma based on Durie-Salmon criteria and/or the diagnostic criteria developed by the International Myeloma Working Group (IMWG).The patient must currently require therapy for relapsed (progressive disease, defined as a 25% increase in M-protein, development of new or worsening of existing lesions or soft tissue plasmacytoma, or hypercalcemia, or relapse from CR. Or patient must have disease that is refractory to most recent therapy. Defined as less than a 50% reduction in serum paraprotein or 90% reduction in urine paraprotein.
- Must have measurable disease, defined as follows: For secretory multiple myeloma, measurable levels of monoclonal protein: greater than or equal to 0.5g/dL on electrophoresis or greater than or equal to 200mg of monoclonal light chain on a 24 hour protein electrophoresis.
- Must have had at least one prior line of therapy but no more than three prior lines of therapy.
- Must understand and voluntarily sign an informed consent form.
- Must be greater than/equal to 18 years of age at time of signing consent.
Key exclusion criteria (19 listed)
- Inability to comply with study and/or follow-up procedures
- Life expectancy of less than 12 weeks
- Inadequately controlled hypertension (defined as systolic blood pressure >150 and/or diastolic blood pressure > 100 mmHg on antihypertensive medications)
- Any prior history of hypertensive crisis or hypertensive encephalopathy
- New York Heart Association (NYHA) Grade II or greater congestive heart failure or left ventricular ejection fraction (LVEF) < 40% (Note: baseline evaluation of LVEF should be performed for any patient who has received >450mg/m2 of any anthracycline during prior chemotherapy.
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: Bortezomib will be administeredBortezomib will be administered at 1.3 mglm2 IVP on Days 1. 4, 8, and 11. Response will be assessed subsequent to each cycle. A total of 8 cycles would beplanned. Patients would be removed subsequent to Cycle 2. if progression of disease is documented. | Drug | Bortezomib and bevacizumab |
Primary outcome
Median Number of Cycles to Tumor Progression (TTP)
Time frame: 18 months
Study Schema: Bortezomib will be administered on Days 1. 4, 8, and 11. Response will be assessed subsequent to each 21-day cycle. Progression is defined using the Bladé criteria, defined progression as an increase of >25% in paraprotein or urinary light chain excretion (or marrow plasma cell percentage in the marrow
Overall Survival (OS) - Number of Participants Alive at Study Completion
Time frame: 18 months
The secondary objective of this study is to assess the safely and tolerability of the combination treatment of bevacizumnab and bortezomnib. Adjustments in the dosing schedule of bortezomib would be made for patients with adequate response as per Blade criteria and continue until disease progression or 18 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Jul 2022.
- 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.
David S Siegel, MD, PhD principal investigator
The Cancer Center at Hackensack University Medical Center
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 Multiple Myeloma, run by Hackensack Meridian Health 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 9 inclusion and 19 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 20 Jul 2022. 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 20 Jul 2022). 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?
Median Number of Cycles to Tumor Progression (TTP) (time frame: 18 months). The study lists 2 primary outcomes in all. 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 20 Jul 2022.