A Phase 2 Study of VEGF Trap (NSC 724770) for the Treatment of Relapsed or Refractory 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

- 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, including any of the following:

- History of cerebrovascular accident within the past 6 months

- Uncontrolled hypertension (i.e., blood pressure [BP] > 150/100 mm Hg or systolic
BP > 180 mm Hg and diastolic BP < 90 mm Hg on ≥ 2 repeated determinations on
separate days within the past 3 months)

- Myocardial infarction, coronary artery bypass graft, or unstable angina within
the past 6 months

- New York Heart Association class III or IV congestive heart failure, serious
cardiac arrhythmia requiring medication, or unstable angina pectoris within the
past 6 months

- Clinically significant peripheral vascular disease within the past 6 months

- Pulmonary embolism, deep vein thrombosis, or other thromboembolic event within
the past 6 months

- 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

- At least 4 weeks since prior radiotherapy or chemotherapy (6 weeks for nitrosoureas
or mitomycin C)

- At least 48 hours since prior minor surgical procedures (e.g., bone marrow aspiration
or biopsy, fine-needle aspiration, placement or removal of a central venous access
device, or biopsy of a skin lesion)

- More than 28 days since prior major surgery or open biopsy

- More than 7 days since prior core biopsy

- Concurrent full-dose anticoagulants (e.g., warfarin) with PT or INR >1.5 allowed
provided the following criteria are met:

- In-range INR (usually between 2 and 3) on a stable dose of oral anticoagulant or
on a stable dose of low molecular weight heparin

- No active bleeding or pathological condition that carries a high risk of
bleeding (e.g., tumor involving major vessels or known varices)

- No concurrent major surgery

- No concurrent immunosuppressive agents (including steroids)

- No other concurrent investigational agents