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

Sponsor:	Genentech
Information provided by (Responsible Party):	Genentech
ClinicalTrials.gov Identifier:	NCT00473590

Purpose

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.

Condition	Intervention	Phase
Multiple Myeloma	Drug: Bevacizumab Drug: Bortezomib Drug: placebo	Phase II

Study Type:	Interventional
Study Design:	Allocation: Randomized Intervention Model: Parallel Assignment Masking: Single Blind (Investigator) Primary Purpose: Treatment
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

Resource links provided by NLM:

Genetics Home Reference related topics: aceruloplasminemia hemophilia

MedlinePlus related topics: Multiple Myeloma

Drug Information available for: Bortezomib Bevacizumab

U.S. FDA Resources

Further study details as provided by Genentech:

Primary Outcome Measures:

Progression-free Survival (PFS) [ Time Frame: From randomization to disease progression or death on study (up to 116 weeks). ] [ Designated as safety issue: No ]
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.

Secondary Outcome Measures:

Number of Participants With an Overall Response [ Time Frame: From randomization to the end of study (clinical cut-off; up to 116 weeks). ] [ Designated as safety issue: No ]
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.
Percentage of Participants With an Overall Response [ Time Frame: From randomization to the end of study (clinical cut-off; up to 116 weeks). ] [ Designated as safety issue: No ]
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.
Duration of Response [ Time Frame: From randomization to the end of study (clinical cut-off; up to 116 weeks). ] [ Designated as safety issue: No ]
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.
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). ] [ Designated as safety issue: No ]
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.
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). ] [ Designated as safety issue: No ]
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.

Enrollment:	102
Study Start Date:	May 2007
Primary Completion Date:	November 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Bortezomib + bevacizumab 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.	Drug: Bevacizumab 15 mg/kg administered by intravenous infusion Drug: Bortezomib 1.3 mg/m^2 administered by intravenous bolus injection
Active Comparator: Bortezomib + placebo 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.	Drug: Bortezomib 1.3 mg/m^2 administered by intravenous bolus injection Drug: placebo Intravenous repeating dose

Arms

Assigned Interventions

Experimental: Bortezomib + bevacizumab

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.

Drug: Bevacizumab

15 mg/kg administered by intravenous infusion

Drug: Bortezomib

1.3 mg/m^2 administered by intravenous bolus injection

Active Comparator: Bortezomib + placebo

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.

Drug: Bortezomib

1.3 mg/m^2 administered by intravenous bolus injection

Drug: placebo

Intravenous repeating dose

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00473590

Sponsors and Collaborators

Genentech

Investigators

Study Director:

Virginia (Ginny) Paton, M.D.

Genentech

More Information

No publications provided

Responsible Party:	Genentech
ClinicalTrials.gov Identifier:	NCT00473590 History of Changes
Other Study ID Numbers:	AVF4064g
Study First Received:	May 14, 2007
Results First Received:	March 31, 2011
Last Updated:	December 13, 2011
Health Authority:	United States: Food and Drug Administration

Keywords provided by Genentech:

Avastin
AMBER
Myeloma
Velcade

Additional relevant MeSH terms:

Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases

Bevacizumab
Bortezomib
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Growth Inhibitors
Antineoplastic Agents
Therapeutic Uses
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on February 09, 2012