Aflibercept for Relapsed Multiple Myeloma

OBJECTIVES:

I. To evaluate the safety and efficacy of VEGF Trap (aflibercept) in patients with relapsed
or refractory, stage II or III multiple myeloma (MM).

II. To perform correlative studies in order to evaluate the angiogenic properties of tissue
from patients during the course of treatment with VEGF Trap.

OUTLINE: This is a multicenter study.

Patients receive aflibercept intravenously (IV) over 1 hour on day 1. Treatment repeats
every 2 weeks for up to 6 courses in the absence of disease progression or unacceptable
toxicity.

After completion of study treatment, patients are followed for 60 days and then periodically
thereafter.

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