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

Genentech

Status and phase: Completed; Phase 2

Conditions: Multiple Myeloma

Treatments: Drug: placebo; Drug: Bortezomib; Drug: Bevacizumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT00473590

AVF4064g

Details and patient eligibility

About

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.

Enrollment: 102 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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102 participants in 2 patient groups

Bortezomib + bevacizumab

Experimental group

Description:

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.

Treatment:

Drug: Bortezomib

Drug: Bevacizumab

Bortezomib + placebo

Active Comparator group

Description:

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.

Treatment:

Drug: placebo

Drug: Bortezomib