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

Study Overview
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Brief Summary
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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.

Detailed Description
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OBJECTIVES: Compare the response rate and time to progression in patients with relapsed or refractory multiple myeloma treated with bevacizumab with or without thalidomide. Compare the toxicity of these regimens in these patients. Compare the effects of these regimens on histological and molecular biomarkers of angiogenesis, tumor invasion, and cell death in these patients. Correlate plasma and urine vascular endothelial growth factor and basic fibroblast growth factor levels and other potential markers of angiogenesis and myeloma cell proliferation with outcome in patients treated with these regimens. Determine the pharmacokinetics of thalidomide in these patients. Compare the effects of these regimens on the psychological/physical well being of these patients. 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. Arm I: Patients receive bevacizumab IV over 30-90 minutes on days 1, 15, 29, and 43. Patients also receive oral thalidomide once daily. Arm II: Patients receive bevacizumab as in arm I. Patients who have received prior treatment with thalidomide receive bevacizumab as in arm I. 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.

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

Conditions
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Multiple Myeloma and Plasma Cell Neoplasm

Intervention / Treatment
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* Biological: bevacizumab
* Drug: thalidomide


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized


Arms and Interventions

| Intervention/Treatment |
| --- |
|Biological: bevacizumab|nan|
|Drug: thalidomide|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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refractory multiple myeloma, stage I multiple myeloma, stage II multiple myeloma, stage III multiple myeloma