Bevacizumab 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 carry cancer-killing substances to them. Bevacizumab may also stop the growth of multiple myeloma by blocking blood flow to the cancer. PURPOSE: This phase II trial is studying how well bevacizumab works in treating patients with relapsed or refractory multiple myeloma.

Detailed Description
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OBJECTIVES: Primary Determine the hematologic response rate in patients with relapsed or refractory multiple myeloma treated with bevacizumab. Determine the proportion of patients who are progression free and have not failed treatment after 1 year. Secondary Determine the toxicity of this drug in these patient. Determine the time to disease progression in patients receiving this drug. Determine the overall survival and survival at 1 year in patients receiving this drug. OUTLINE: This is an open-label study. Patients receive bevacizumab IV on day 1. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. Blood samples are obtained for correlative studies at baseline, after course 2, and at 12 weeks. Samples are analyzed for interleukin-6, Flt-1, and VEGF levels. After completion of study therapy, patients are followed every 3-6 months for up to 3 years.

Official Title
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A Phase II Trial of Bevacizumab in Patients With Relapsed or Refractory Multiple Myeloma

Conditions
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Multiple Myeloma and Plasma Cell Neoplasm

Intervention / Treatment
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* Biological: bevacizumab
* Genetic: gene expression analysis
* Genetic: protein expression analysis
* Other: laboratory biomarker analysis


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Diagnosis of relapsed or refractory multiple myeloma Measurable or evaluable disease as defined by ≥ 1 of the following: Serum monoclonal protein ≥ 1.0 g by protein electrophoresis Monoclonal protein ≥ 200 mg by 24-hour urine electrophoresis Serum immunoglobulin free light chain ≥ 10 mg/dL AND abnormal serum immunoglobulin kappa to lambda free light chain ratio Monoclonal bone marrow plasmacytosis ≥ 30% (evaluable disease) No concurrent amyloidosis PATIENT CHARACTERISTICS: ECOG performance status (PS) 0 or 1 ECOG PS 2 based on immobility from myeloma bone disease alone allowed at the discretion of treating physician Creatinine ≤ 2.0 mg/dL ANC ≥ 1,000/mm³ Platelet count ≥ 75,000/mm³ Hemoglobin ≥ 8.0 g/dL Proteinuria ≤ 1 g/dL by 24-hour urine collection (excluding monoclonal protein) Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception during and for 4 weeks after completion of study treatment No bleeding diathesis No hypertension (defined as BP > 150/100 mm Hg) No active bleeding, healing or nonhealing wound, ulcer, or bone fracture (excluding fractures secondary to myeloma) No active ulcerative disease including, but not limited to, any of the following: Peptic ulcer disease Ulcerative esophagitis Ulcerative colitis Crohn's disease LVEF ≥ 50% by 2-dimensional ECHO or MUGA scan No NYHA class III or IV heart disease No other active malignancy except for nonmelanoma skin cancer or in situ cervical or breast cancer No active infection No other comorbidity that would interfere with study compliance No transient ischemic attack, cerebrovascular accident, or myocardial infarction within the past year No abdominal fistula, gastrointestinal perforation, or intraabdominal abscess within the past 6 months No significant traumatic injury within the past 28 days PRIOR CONCURRENT THERAPY: See Disease Characteristics No more than 2 prior antimyeloma treatment courses, except for bisphosphonates No standard or experimental drug therapy, other than ongoing bisphosphonate treatment and/or epoetin alfa, within the past 28 days No experimental non-drug therapy within the past 28 days Palliative radiation therapy within the past 28 days allowed provided ≤ 3 sites of bone disease was irradiated No prior bevacizumab or other experimental antiangiogenic agents other than thalidomide or lenalidomide No minor surgical procedures, fine-needle aspiration, or core biopsies within the past 7 days No major surgical procedure or open biopsy within the past 28 days No concurrent corticosteroids Chronic steroids ≤ 20 mg/day (prednisone equivalent) for disorders other than myeloma (i.e., adrenal insufficiency, rheumatoid arthritis) allowed No other concurrent investigational therapy No other concurrent systemic antineoplastic therapy including, but not limited to, the following: Cytotoxic chemotherapy Immunotherapy Hormonal therapy Monoclonal antibody therapy 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
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Biological: bevacizumab|nan|
|Genetic: gene expression analysis|nan|
|Genetic: protein expression analysis|nan|
|Other: laboratory biomarker analysis|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Confirmed hematologic response |  |  | 
| Progression-free survival at 1 year |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Toxicity as measured by NCI CTCAE v3.0 |  |  | 
| Time to progression |  |  | 
| Duration of response |  |  | 
| Survival |  |  | 

 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