Phase II Trial of Bevacizumab Combined With Lenalidomide and Dexamethasone (BEV/REV/DEX) in Relapsed or Refractory Multiple Myeloma
I. Determine the overall response rate (complete response and partial response) in patients
with relapsed or refractory stage II or III multiple myeloma treated with bevacizumab,
lenalidomide, and dexamethasone.
I. Determine time to progression in these patients. II. Determine the toxicity and
tolerability of this regimen. III. Determine the effect of bevacizumab and lenalidomide on
markers of myeloma activity in myeloma cells and stromal cells, including interleukin-6,
macrophage inflammatory protein-1α, vascular endothelial growth factor, and STAT3.
IV. Assess local cytokine milieu using tissue microarrays of bone marrow biopsy specimens.
OUTLINE: This is a multicenter, open-label study.
Patients receive bevacizumab IV over 30-90 minutes on days 1 and 15, oral lenalidomide on
days 1-21, and oral dexamethasone on days 1, 8, 15, and 22. Courses repeat every 4 weeks in
the absence of disease progression or unacceptable toxicity.
Blood samples are collected at baseline and before courses 2 and 4. Blood samples are
examined for vascular endothelial growth factor (VEGF) and VEGF receptor (VEGFR)
polymorphisms by pyrosequencing and VEGF, VEGFR1, VEGFR2, interleukin-6, and macrophage
inflammatory protein 1 by immunoenzyme techniques. Relationships between plasma cell myeloma
and stroma and the effect of study treatment on these relationships are examined in tissue
sections of bone marrow before and after treatment utilizing microvessel density
measurements, VEGF staining, and STAT3 staining (by immunohistochemistry and fluorescent in
situ hybridization [FISH]).
After completion of study treatment, patients are followed periodically for at least 5
Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Confirmed anti-tumor response rate (complete response and partial response) to the combination of bevacizumab and lenalidomide
Responses will be analyzed by descriptive statistics and summarized in tabular format (frequency tables). Furthermore, two-sided 95% confidence intervals for the proportions of subjects with a confirmed anti-tumor response will be computed using the method proposed by Chang, which takes into account the multiplicity problem associated with the two-stage testing procedure. The objective response rate will be estimated by using Whitehead's bias-adjustment approach.
Up to 5 years
University of Wisconsin Hospital and Clinics
United States: Food and Drug Administration
|University of Pittsburgh Cancer Institute||Pittsburgh, Pennsylvania 15213|
|University of Wisconsin Hospital and Clinics||Madison, Wisconsin 53792-0001|