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

Multiple Myeloma Clinical Trial

— AMBER  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00473590
• Other study ID #: AVF4064g
• Status: Completed
• Phase: Phase 2
• First received: May 14, 2007
• Last updated: December 13, 2011
• Start date: May 2007

Study information

• Verified date: December 2011
• Source: Genentech, Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 102
• Est. primary completion date: November 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

• 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

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Single Blind (Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell

Intervention

Drug:
• Bevacizumab
15 mg/kg administered by intravenous infusion
• Bortezomib
1.3 mg/m^2 administered by intravenous bolus injection
• placebo
Intravenous repeating dose

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Genentech, Inc.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	From randomization to disease progression or death on study (up to 116 weeks).	No
Secondary	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.	From randomization to the end of study (clinical cut-off; up to 116 weeks).	No
Secondary	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.	From randomization to the end of study (clinical cut-off; up to 116 weeks).	No
Secondary	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.	From randomization to the end of study (clinical cut-off; up to 116 weeks).	No
Secondary	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.	From randomization until death from any cause, up until the end of study (clinical cut-off; up to 116 weeks).	No
Secondary	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.	Participants were monitored for AEs from initiation of treatment to 30 days after treatment termination (up to 122 weeks).	No