Phase II Randomized Trial of Bevacizumab Versus Bevacizumab and Thalidomide for Relapsed/Refractory Multiple Myeloma
Phase II Randomized Trial of Bevacizumab Versus Bevacizumab and Thalidomide for Relapsed/Refractory Multiple Myeloma
RATIONALE: Monoclonal antibodies, such as bevacizumab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or deliver cancer-killing substances to them. Thalidomide may stop the growth of cancer cells by stopping blood flow to the tumor. It is not yet known whether bevacizumab works better with or without thalidomide for multiple myeloma.
PURPOSE: This randomized phase II trial is to see if bevacizumab works better with or without thalidomide in treating patients who have relapsed or refractory multiple myeloma.
OBJECTIVES:
OUTLINE: This is a randomized, multicenter study. Patients are stratified according to prior treatment with thalidomide (yes vs no).
Patients who have received no prior treatment with thalidomide are randomized to 1 of 2 treatment arms.
Courses repeat every 56 days in the absence of disease progression or unacceptable toxicity.
Patients are followed monthly for 3 months and then every 3-4 months for 3 years.
PROJECTED ACCRUAL: A total of 55-103 patients (16-32 who have received prior thalidomide, 16-32 in arm I, and 23-39 in arm II) will be accrued for this study within 2.5 years.
DISEASE CHARACTERISTICS:
Histologically confirmed progressing multiple myeloma
Smoldering myeloma is eligible provided there is evidence of progressive disease requiring therapy
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:
Performance status:
Life expectancy:
Hematopoietic:
Hepatic:
Renal:
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:
Pulmonary:
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
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:
Concurrent epoetin alfa allowed if started at least 4 weeks prior to study entry
Chemotherapy:
No more than 5 prior chemotherapy regimens
At least 3 weeks since prior chemotherapy
No concurrent chemotherapy
Endocrine therapy:
Radiotherapy:
Surgery:
Other: