Aflibercept for Relapsed Multiple Myeloma

Inclusion Criteria:

Histologically or cytologically confirmed multiple myeloma

Stage II or III disease according to Salmon-Durie staging criteria
Relapsed or refractory disease
Progressive disease

Measurable disease, defined by ≥ 1 of the following criteria:

Serum M protein ≥ 1.0 g/dL by serum protein electrophoresis
Free light chain measurement > 200 mg/dL
Urinary M protein excretion ≥ 200 mg/24 hours

Must have received ≥ 2 prior therapies* for multiple myeloma that meet the following criteria:

Antimyeloma therapeutic regimen consisting of ≥ 1 complete course of single-agent or combination-agent therapy, or a planned series of treatments (e.g., 3-4 courses of induction therapy followed by a stem cell harvest procedure followed by conditioning high-dose therapy supported by stem cell transplantation)
Antimyeloma regimen is discontinued because of the development of resistant disease or severe therapy-related toxicity
Individual antimyeloma regimen will be considered to have been discontinued when all agents of the regimen have been permanently stopped
A prior regimen will not be considered to have been discontinued for the modification of drug doses, or if less than all the agents of a combination regimen have been discontinued, or if the regimen has been halted temporarily for the development of a plateau phase of myeloma
Maintenance therapy will not be considered an additional regimen
If new agents are added to an existing regimen, presumably because of tumor resistance, the old regimen will be considered to have ended and a new regimen to have started
No evidence of central nervous system (CNS) disease, including primary brain tumor or brain metastasis
Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2 OR Karnofsky PS 60-100%
Life expectancy > 12 weeks
White blood cell (WBC) ≥ 3,000/mm^3
Absolute neutrophil count ≥ 1,500/mm^3
Platelet count ≥ 75,000/mm^3
Bilirubin ≤ 1.5 times upper limit of normal (ULN)
Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 times ULN
Creatinine ≤ 2.0 mg/dL OR creatinine clearance ≥ 60 mL/min

No albuminuria only

Urine protein: creatinine ratio < 1 OR 24-hour urine protein with an albumin level < 500 mg
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception during and for ≥ 6 months after completion of study therapy

Exclusion criteria:

No known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies
No known history of allergic reactions attributed to compounds of similar chemical or biological composition to other agents used in the study
No serious or nonhealing wound, ulcer, or bone fracture
No significant traumatic injury within the past 28 days
No abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 28 days
No clinically significant cardiovascular disease
No prothrombin time (PT) or international normalized ratio (INR) > 1.5 (unless patient is on full-dose warfarin)
No evidence of bleeding diathesis or coagulopathy
No uncontrolled intercurrent illness that would limit compliance with study requirements, including ongoing or active infection
No psychiatric illness or social situations that would limit study compliance
No concurrent major surgery
No concurrent immunosuppressive agents (including steroids)
No other concurrent investigational agents