Phase II Randomized Trial of Bevacizumab Versus Bevacizumab and Thalidomide for Relapsed/Refractory Multiple Myeloma

Inclusion Criteria

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