Phase II Trial of Bevacizumab Combined With Lenalidomide and Dexamethasone (BEV/REV/DEX) in Relapsed or Refractory Multiple Myeloma

Inclusion Criteria:

- Histologically or cytologically confirmed symptomatic multiple myeloma:

- Stage II or III disease

- Relapsed or refractory disease after >= 2 courses of prior chemotherapy

- Measurable levels of monoclonal protein (M protein) > 1.0 g/dL by serum protein
electrophoresis OR > 200 mg of monoclonal light chain by 24-hour urine protein
electrophoresis

- Measurable bone disease, defined as >= 1 unidimensionally measurable lesion (longest
diameter to be recorded) >= 20 mm with conventional techniques OR >= 10 mm with
spiral CT scan (for patients with lytic bone disease)

- No known brain metastases

- ECOG performance status (PS) 0-2 OR Karnofsky PS 70-100%

- Patients with PS of 3 are eligible if it is due to pain that is likely to
improve with treatment

- Life expectancy > 6 months

- No known HIV positivity

- No abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within
the past 6 months

- No active infections requiring oral or intravenous antibiotics within the past week

- No proteinuria (i.e., albuminuria) > 1,000 mg/24 hours unless related to the
diagnosis of multiple myeloma

- Patients with light chain (i.e., "Bence-Jones") proteinuria are still eligible
if the non-light chain component of protein is < 1,000 mg/24 hours

- No serious nonhealing wound or ulcer

- No blood pressure > 150/90 mm Hg (even with medication)

- No significant traumatic injury within the past 28 days

- No clinically significant peripheral vascular disease

- No evidence of bleeding diathesis or coagulopathy

- No unstable angina or myocardial infarction within the past 6 months

- No stroke within the past 6 months

- No New York Heart Association class III or IV heart failure

- No secondary malignancy within the past 2 years except squamous cell or basal cell
carcinoma of the skin or carcinoma in situ of the cervix

- Hemoglobin > 9 g/dL (may be supported by transfusion or growth factors)

- WBC >= 2,000/mm^3

- Absolute neutrophil count >= 1,000/mm^3

- Platelet count >= 75,000/mm^3

- Bilirubin =< 2.5 mg/dL

- At least 4 weeks since prior chemotherapy or radiotherapy and recovered

- More than 7 days since prior minor surgical procedures, fine-needle aspirations, or
core biopsies:

More than 24 hours since prior bone marrow biopsy or central veinous access placement

- More than 28 days since prior major surgical procedure or open biopsy

- At least 4 weeks since prior and no concurrent participation in another experimental
drug study

- Prior autologous peripheral blood stem cell transplantation allowed

- No prior lenalidomide

- Concurrent full-dose anticoagulants allowed provided all of the following criteria
are met:

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

- No thrombocytopenia requiring transfusion

- Platelet count > 75,000/mm3

- INR 2-3 and stable

- No concurrent major surgery

- No concurrent sargramostim (GM-CSF)

- No other concurrent investigational agents

- No other concurrent anticancer agents or therapies

- AST and ALT =< 5 times upper limit of normal

- Creatinine < 2.5 mg/dL

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use 2 methods of effective contraception 4 weeks before,
during, and 4 weeks after completion of study treatment

- No history of allergic reactions attributed to compounds of similar chemical or
biological composition to lenalidomide and/or bevacizumab or other agents used in the
study