Bevacizumab With or Without Thalidomide in Treating Patients With Relapsed or Refractory Multiple Myeloma

DISEASE CHARACTERISTICS:

• Histologically confirmed progressing multiple myeloma
• Stages I, II, or III
• More than 25% increase in urine or plasma paraprotein levels
• More than 5% malignant plasma cell involvement in bone marrow
• Smoldering myeloma is eligible provided there is evidence of progressive disease requiring therapy
• At least 25% increase in M protein levels or Bence Jones excretion
• Hemoglobin no greater than 10.5 g/dL
• Frequent infections
• Hypercalcemia
• Rise in serum creatinine above normal on 2 separate occasions
• Nonsecretory multiple myeloma that is bidimensionally measurable by MRI or CT scan is eligible provided the disease site is new or has shown an increase in M protein levels or Bence Jones excretion is greater than 30% from baseline
• No prior or concurrent CNS involvement with primary or metastatic tumor
• No nonquantifiable monoclonal proteins or IgM peaks unless there is evidence of bidimensionally measurable disease by MRI or CT scan
• No history of hemorrhagic tumor or hemorrhagic metastasis

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• Karnofsky 70-100%

Life expectancy:

• At least 3 months

Hematopoietic:

• See Disease Characteristics
• Absolute neutrophil count ≥1,000/mm^3
• Platelet count ≥ 50,000/mm^3
• No hemorrhagic illness within the past 3 weeks

Hepatic:

• Bilirubin ≤ 1.5 mg/dL
• SGOT/SGPT≤ 2.5 times upper limit of normal (ULN)
• INR ≤ 1.5
• aPTT < 1.5 times ULN

Renal:

• See Disease Characteristics
• Creatinine ≤ 2 mg/dL
• Creatinine clearance ≥ 40 mL/min
• Calcium ≤ 12 mg/dL
• No nephrotic syndrome

Cardiovascular:

• No active coronary artery disease
• No New York Heart Association class II-IV congestive heart failure
• No grade II or greater peripheral vascular disease (i.e, ischemic rest pain, non-healing ulcer, or tissue loss)
• No uncontrolled hypertension
• No history of deep venous thrombosis
• No vascular illness within the past 3 weeks
• No arterial thromboembolic event within the past 6 months, including any of the following:
• Transient ischemic attack
• Cerebrovascular accident
• Unstable angina
• Myocardial infarction

Pulmonary:

• No history of pulmonary embolus

Other:

• No other prior malignancy unless the patient has been in complete remission for at least 2 years
• No peripheral neuropathy or CNS abnormalities ≥ grade 2
• Patients with prior exposure to thalidomide and assigned to arm I may have grade 2 peripheral or CNS abnormalities
• No seizure disorder
• No serious non-healing wound, ulcer, or bone fracture
• No trauma within the past 3 weeks
• No significant inflammatory illness within the past 3 weeks
• No known hypersensitivity to Chinese hamster ovary cell products
• No known hypersensitivity to other recombinant human or humanized antibodies and/or positive human antimurine antibodies/human antichimeric antibodies
• No other significant medical, psychological, or social problem that would preclude study participation
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception for at least 2 weeks before and during study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• See Chemotherapy
• Prior nonmyeloablative transplantation allowed provided the following are true:
• Patient is not receiving concurrent immunosuppressive therapy
• Patient has no signs of graft-versus-host disease
• Concurrent epoetin alfa allowed if started at least 4 weeks prior to study entry

Chemotherapy:

• No more than 5 prior chemotherapy regimens
• Thalidomide, steroids, and interferon are not considered part of prior regimens
• Mobilization with chemotherapy followed by either single or tandem autologous transplantation is counted as 1 prior regimen
• Mobilization with chemotherapy followed by autologous and subsequent nonmyeloablative HLA-matched sibling allogeneic transplantation is counted as 1 prior regimen
• At least 3 weeks since prior chemotherapy
• No concurrent chemotherapy

Endocrine therapy:

• See Chemotherapy
• At least 2 weeks since prior steroids
• No concurrent steroids

Radiotherapy:

• At least 3 weeks since prior radiotherapy
• No concurrent radiotherapy

Surgery:

• At least 3 weeks since prior surgery, including biopsy of a visceral organ

Other:

• At least 10 days since prior anticoagulants, including aspirin
• At least 2 days since prior nonsteroidal anti-inflammatory agents
• Concurrent bisphosphonates allowed