A Study of Bevacizumab in Combination With Bortezomib in Patients With Relapsed or Refractory Multiple Myeloma (AMBER)

A Phase 2 study testing Bevacizumab and Bortezomib in people with Multiple Myeloma, run by Genentech, Inc..

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Trial summary

This is a randomized, blinded, placebo-controlled, multicenter, Phase II study designed to provide a preliminary assessment of the safety and efficacy of combining bevacizumab with bortezomib in patients with relapsed or refractory multiple myeloma. 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?: Bevacizumab and Bortezomib
Type of treatment: Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 102 participants
Where: No sites listed yet
Study dates: Jun 2007to Nov 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
No healthy volunteers
Adult, Older adult

Who may be able to join

Age ≥ 18 years
Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
Previously diagnosed with multiple myeloma
Relapsed or refractory multiple myeloma with disease progression following one to three prior treatment regimens
Measurable multiple myeloma disease

Who cannot join

Grade ≥ 2 peripheral neuropathy
Use of corticosteroids within 21 days prior to Day 1
Use of other anti-myeloma therapy within 21 days prior to Day 1
Intolerance to bortezomib or compounds containing boron
Life expectancy of < 12 weeks
Current, recent, or planned participation in an experimental drug study

Show all 23Show fewer

Active malignancy other than multiple myeloma within 5 years before screening
Prior treatment with bevacizumab
Inadequately controlled hypertension
Prior history of hypertensive crisis or hypertensive encephalopathy
New York Heart Association (NYHA) Class II or greater congestive heart failure (CHF)
Decreased left ventricular function at study entry
History of myocardial infarction or unstable angina within 6 months prior to Day 1
History of stroke or transient ischemic attack within 6 months prior to Day 1
Significant vascular disease or recent peripheral arterial thrombosis within 6 months prior to Day 1
Evidence of bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation)
Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 1, or anticipation of need for major surgical procedure during the course of the study
Core biopsy or other minor surgical procedure, including placement of a vascular access device within 7 days prior to Day 1
History of abdominal fistula or gastrointestinal perforation within 6 months prior to Day 1
Serious, non-healing wound, active ulcer, or untreated bone fracture (for pathologic bone fractures consistent with multiple myeloma, patients may be eligible if no treatment is planned)
Albuminuria
Known hypersensitivity to any component of bevacizumab
Pregnancy (positive pregnancy test) or lactation

About this study

Official title: A Randomized, Blinded, Placebo-Controlled, Multicenter, Phase II Study of Bevacizumab in Combination With Bortezomib in Patients With Relapsed or Refractory Multiple Myeloma

Conditions: Multiple Myeloma
Being tested: Bevacizumab, Bortezomib, placebo
Keywords: Avastin, AMBER, Myeloma, Velcade
Medical subject headings: Multiple Myeloma, Neoplasms, Plasma Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

BevacizumabDrug
15 mg/kg administered by intravenous infusion
BortezomibDrug
1.3 mg/m^2 administered by intravenous bolus injection
placeboDrug
Intravenous repeating dose

Study groups in NCT00473590
Study group	Role	What they receive
Bortezomib + bevacizumab	Experimental	Participants received bortezomib 1.3 mg/m^2 administered as a 3- to 5-second bolus intravenous injection on Days 1, 4, 8, and 11 of a 21-day cycle for a maximum of eight cycles and bevacizumab 15 mg/kg administered by intravenous infusion on the first day of each 21-day cycle during the blinded treatment phase. After completion of 8 cycles, participants could continue to receive bevacizumab as monotherapy until disease progression. Receives: Drug: Bevacizumab; Drug: Bortezomib
Bortezomib + placebo	Active comparator	Participants received bortezomib 1.3 mg/m^2 administered as a 3- to 5-second bolus intravenous injection on Days 1, 4, 8, and 11 of a 21-day cycle for a maximum of eight cycles and placebo intravenous infusion on the first day of each 21-day cycle during the blinded treatment phase. At the completion of the 8-cycle treatment phase, participants entered the observation phase until disease progression. Receives: Drug: Bortezomib; Drug: placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

Progression-free Survival (PFS)
Progression-free survival (PFS) was defined as the time from randomization to disease progression or death on study from any cause within 30 days of the last response assessment. Disease progression was determined by the investigator using the International Myeloma Working Group's (IMWG) uniform response criteria. Median PFS was estimated using Kaplan-Meier methodology. For patients who were alive at the time of the analysis and whose disease had not yet progressed, PFS was censored at the time of the last response assessment.
Measured: From randomization to disease progression or death on study (up to 116 weeks).

Secondary outcomes (5)

Number of Participants With an Overall Response
Overall response was defined as a stringent complete response, complete response, very good partial response, or partial response (sCR, CR, VGPR, and PR, respectively) determined on two consecutive assessments ≤ 6 weeks apart and before the initiation of any new anti-tumor therapy, as assessed by the investigator using the International Myeloma Working Group's (IMWG's) uniform response criteria. Patients without a post-baseline response assessment or who died prior to their first scheduled response assessment were considered non-responders.
Measured: From randomization to the end of study (clinical cut-off; up to 116 weeks).
Percentage of Participants With an Overall Response
Overall response was defined as a stringent complete response, complete response, very good partial response, or partial response (sCR, CR, VGPR, and PR) determined on two consecutive assessments ≤ 6 weeks apart and before the initiation of any new anti-tumor therapy, as assessed by the investigator using the IMWG's uniform response criteria. Patients without a post-baseline response assessment or who died prior to their first scheduled response assessment were considered non-responders.
Measured: From randomization to the end of study (clinical cut-off; up to 116 weeks).
Duration of Response
Duration of response was defined as the time from the initial response to disease progression or death on study. Disease progression was determined by the investigator using the IMWG's uniform response criteria and defined as an increase of ≥25% from best response in: Serum M-protein and/or Urine M-protein and/or Marrow plasma cells; or new or increased plasmacytomas or bone lesions; or hypercalcemia due to myeloma. Duration of response was estimated using Kaplan-Meier. For patients who had not progressed or died, duration of response was censored at the date of the last response assessment.
Measured: From randomization to the end of study (clinical cut-off; up to 116 weeks).
Overall Survival (OS)
Overall survival was defined as the duration of time from randomization until death from any cause. All deaths were included, whether they occurred on study treatment or following treatment discontinuation. Overall survival was estimated using Kaplan-Meier. For patients who had not died, overall survival was censored at the date that the patient was last known to be alive.
Measured: From randomization until death from any cause, up until the end of study (clinical cut-off; up to 116 weeks).
Number of Participants With Selected Adverse Events (AEs)
Adverse events were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), v3.0. All serious adverse events are listed in the Adverse Event Reporting section.
Measured: Participants were monitored for AEs from initiation of treatment to 30 days after treatment termination (up to 122 weeks).

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Jun 2007Nov 2009

First posted15 May 2007 (estimated)
Study startJun 2007
Primary completionNov 2009
Study completionNov 2009

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.
More trials run by Genentech, Inc.The 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: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Single blind
Who is masked: Investigator
Enrolment: 102 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00473590
Sponsor's protocol ID: AVF4064g
Acronym: AMBER
Status last verified: May 2017
First submitted: 14 May 2007
Last updated: 14 Jun 2017
Results posted: Yes, on ClinicalTrials.gov

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

Official record

Not yet recruitingPhase 2
Study of YKST02 in Adults With Relapsed or Refractory Multiple Myeloma
Relapsed or Refractory Multiple Myeloma (RRMM)
RecruitingPhase 2
Engaging T-cells to Eliminate MRD in Newly Diagnosed Myeloma Optimizing Response With Talquetmab and Teclistamab (ROTATE)
Multiple Myeloma
Active, not recruitingPhase 3
A Phase III Study of Eque-cel in Subjects With Len-refractory RRMM (FUMANBA-03)
Multiple Myeloma
Active, not recruitingPhase 1/2
A Window of Opportunity Trial to Learn if Linvoseltamab is Safe and Well Tolerated, and How Well it Works in Adult Participants With Recently Diagnosed Multiple Myeloma Who Have Not Already Received Treatment
Multiple Myeloma
Active, not recruitingPhase 2
Testing AZD5363 as a Potential Targeted Treatment in Cancers With AKT Genetic Changes (MATCH-Subprotocol Y)
Advanced Lymphoma, Advanced Malignant Solid Neoplasm

All Multiple Myeloma trials

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: A Randomized, Blinded, Placebo-Controlled, Multicenter, Phase II Study of Bevacizumab in Combination With Bortezomib in Patients With Relapsed or Refractory Multiple Myeloma
ClinicalTrials.gov ID: NCT00473590
Acronym / sponsor ID: AMBER / AVF4064g
Conditions: Multiple Myeloma
Keywords: Avastin, AMBER, Myeloma, Velcade
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 102 participants (actual)
Lead sponsor: Genentech, Inc.Industry (pharma, biotech, devices)
Study start: Jun 2007 (actual)
Primary completion: Nov 2009 (actual)
Study completion: Nov 2009 (actual)
First posted: 15 May 2007 (estimated)
Results: Posted 19 Jan 2012

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Single blind (investigator)
Number of arms: 2

Arm	Type	Receives
Bortezomib + bevacizumab	Experimental	Drug: Bevacizumab, Drug: BortezomibParticipants received bortezomib 1.3 mg/m^2 administered as a 3- to 5-second bolus intravenous injection on Days 1, 4, 8, and 11 of a 21-day cycle for a maximum of eight cycles and bevacizumab 15 mg/kg administered by intravenous infusion on the first day of each 21-day cycle during the blinded treatment phase. After completion of 8 cycles, participants could continue to receive bevacizumab as monotherapy until disease progression.
Bortezomib + placebo	Active comparator	Drug: Bortezomib, Drug: placeboParticipants received bortezomib 1.3 mg/m^2 administered as a 3- to 5-second bolus intravenous injection on Days 1, 4, 8, and 11 of a 21-day cycle for a maximum of eight cycles and placebo intravenous infusion on the first day of each 21-day cycle during the blinded treatment phase. At the completion of the 8-cycle treatment phase, participants entered the observation phase until disease progression.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (5 listed)

Age ≥ 18 years
Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
Previously diagnosed with multiple myeloma
Relapsed or refractory multiple myeloma with disease progression following one to three prior treatment regimens
Measurable multiple myeloma disease

Key exclusion criteria (23 listed)

Grade ≥ 2 peripheral neuropathy
Use of corticosteroids within 21 days prior to Day 1
Use of other anti-myeloma therapy within 21 days prior to Day 1
Intolerance to bortezomib or compounds containing boron
Life expectancy of < 12 weeks

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
Bevacizumab15 mg/kg administered by intravenous infusion	Drug	Bortezomib + bevacizumab
Bortezomib1.3 mg/m^2 administered by intravenous bolus injection	Drug	Bortezomib + bevacizumab, Bortezomib + placebo
placeboIntravenous repeating dose	Drug	Bortezomib + placebo

Primary outcome

Progression-free Survival (PFS)
Time frame: From randomization to disease progression or death on study (up to 116 weeks).
Progression-free survival (PFS) was defined as the time from randomization to disease progression or death on study from any cause within 30 days of the last response assessment. Disease progression was determined by the investigator using the International Myeloma Working Group's (IMWG) uniform response criteria. Median PFS was estimated using Kaplan-Meier methodology. For patients who were alive at the time of the analysis and whose disease had not yet progressed, PFS was censored at the time of the last response assessment.

5 secondary outcomes

Number of Participants With an Overall Response
Time frame: From randomization to the end of study (clinical cut-off; up to 116 weeks).
Percentage of Participants With an Overall Response
Time frame: From randomization to the end of study (clinical cut-off; up to 116 weeks).
Duration of Response
Time frame: From randomization to the end of study (clinical cut-off; up to 116 weeks).
Overall Survival (OS)
Time frame: From randomization until death from any cause, up until the end of study (clinical cut-off; up to 116 weeks).
Number of Participants With Selected Adverse Events (AEs)
Time frame: Participants were monitored for AEs from initiation of treatment to 30 days after treatment termination (up to 122 weeks).

Results and safety

Results posted to the registry on 19 Jan 2012, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
BORT + P	53	8
BORT + BV	49	11

Primary outcome: Progression-free Survival (PFS)

Time frame: From randomization to disease progression or death on study (up to 116 weeks).. Median (95% Confidence Interval). Unit: months

Measure	BORT + P n = 53	BORT + BV n = 49
Value	5.1 (4.17 to 7.20)	6.2 (4.40 to 8.54)

BORT + P vs BORT + BV: Hazard Ratio (HR): 0.743 (95% CI 0.432 to 1.276), p = 0.2804, Log Rank
BORT + P vs BORT + BV: Hazard Ratio (HR): 0.713 (95% CI 0.424 to 1.200), p = 0.2009, Log Rank

Population analysed: Randomized Patients

5 secondary outcomes are reported in the full results.

Adverse events

Time frame: Participants were monitored for AEs from initiation of treatment to 30 days after treatment termination.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
BORT + P	26 of 50 (52%)	41 of 50 (82%)	Not reported
BORT + BV	24 of 50 (48%)	43 of 50 (86%)	Not reported

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.

Related trials for Multiple Myeloma

Not yet recruitingPhase 2
Study of YKST02 in Adults With Relapsed or Refractory Multiple Myeloma
Relapsed or Refractory Multiple Myeloma (RRMM)
RecruitingPhase 2
Engaging T-cells to Eliminate MRD in Newly Diagnosed Myeloma Optimizing Response With Talquetmab and Teclistamab (ROTATE)
Multiple Myeloma
Active, not recruitingPhase 3
A Phase III Study of Eque-cel in Subjects With Len-refractory RRMM (FUMANBA-03)
Multiple Myeloma
Active, not recruitingPhase 1/2
A Window of Opportunity Trial to Learn if Linvoseltamab is Safe and Well Tolerated, and How Well it Works in Adult Participants With Recently Diagnosed Multiple Myeloma Who Have Not Already Received Treatment
Multiple Myeloma
Active, not recruitingPhase 2
Testing AZD5363 as a Potential Targeted Treatment in Cancers With AKT Genetic Changes (MATCH-Subprotocol Y)
Advanced Lymphoma, Advanced Malignant Solid Neoplasm

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.

Virginia (Ginny) Paton, M.D. study director

Genentech, Inc.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Bevacizumab and Bortezomib in people with Multiple Myeloma, run by Genentech, Inc..

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 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: finished, 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.

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 19 Jan 2012). 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?

Progression-free Survival (PFS) (time frame: From randomization to disease progression or death on study (up to 116 weeks).). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00473590.

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.