A Phase II Study of Bevacizumab and Bortezomib in Patients With Relapsed/Refractory Multiple Myeloma

Inclusion Criteria:

- Must have been previously diagnosed with multiple myeloma based on Durie-Salmon
criteria and/or the diagnostic criteria developed by the International Myeloma
Working Group (IMWG).The patient must currently require therapy for relapsed
(progressive disease, defined as a 25% increase in M-protein, development of new or
worsening of existing lesions or soft tissue plasmacytoma, or hypercalcemia, or
relapse from CR. Or patient must have disease that is refractory to most recent
therapy. Defined as less than a 50% reduction in serum paraprotein or 90% reduction
in urine paraprotein.

- Must have measurable disease, defined as follows: For secretory multiple myeloma,
measurable levels of monoclonal protein: greater than or equal to 0.5g/dL on
electrophoresis or greater than or equal to 200mg of monoclonal light chain on a 24
hour protein electrophoresis.

- Must have had at least one prior line of therapy but no more than three prior lines
of therapy.

- Must understand and voluntarily sign an informed consent form.

- Must be greater than/equal to 18 years of age at time of signing consent.

- Must be able to adhere to study visit schedule and other protocol requirements.

- Must have an ECOG performance status of 0,1or 2

- Women of Child-bearing potential (WCBP) defined as a sexually mature woman who has
not undergone a hysterectomy or who has not been naturally post-menopausal for at
least 24 consecutive months must have a negative serum or urine pregnancy test within
7 days of starting study drug. In addition, sexually active WCBP must agree to use
adequate contraceptive methods (oral, injectable, or implantable hormonal
contraceptive method; tubal ligation; intra-uterine device; barrier contraceptive
with spermicide; or vasectomized partner) while on study medication.

- All WCBP and all sexually active male patients must agree to use adequate methods of
birth control throughout the study.

Exclusion Criteria:

- Inability to comply with study and/or follow-up procedures

- Life expectancy of less than 12 weeks

- Inadequately controlled hypertension (defined as systolic blood pressure >150 and/or
diastolic blood pressure > 100 mmHg on antihypertensive medications)

- Any prior history of hypertensive crisis or hypertensive encephalopathy

- New York Heart Association (NYHA) Grade II or greater congestive heart failure or
left ventricular ejection fraction (LVEF) < 40% (Note: baseline evaluation of LVEF
should be performed for any patient who has received >450mg/m2 of any anthracycline
during prior chemotherapy.

- History of myocardial infarction or unstable angina within 6 months prior to study
enrollment

- History of stroke or transient ischemic attack within 6 months prior to study
enrollment

- Known CNS disease

- Significant vascular disease (e.g., aortic aneurysm, aortic dissection)

- Symptomatic peripheral vascular disease

- Known hypersensitivity to any component of bevacizumab and/or bortezomib

- Previously treated with Bortezomib and/or Bevacizumab.

- Received nitrosoureas within 3 weeks or any other chemotherapy, including thalidomide
or clarithromycin, or radiation therapy before enrollment.

- Received corticosteroids (greater than 10mg/day prednisone or equivalent) within
three weeks prior to enrollment.

- Received immunotherapy or antibody therapy within 8 weeks prior to enrollment.

- Received plasmapheresis within 4 weeks before enrollment.

- Had major surgery within 4 weeks before enrollment. (kyphoplasty is not considered
major surgery)

- History of allergic reactions attributable to compounds containing boron or mannitol.

- Grade 3 or greater peripheral neuropathy as defined by the NCI Common Toxicity
Criteria (NCI CTC version 3.0) Grade 3: Sensory loss or paresthesia interfering with
ADLs. Grade 4: Permanent sensory loss that interferes with function.