Conditions: Multiple Myeloma
Keywords: multiple myeloma myeloma relapsed myeloma refractory myeloma relapsed, refractory myeloma relapsed, refractory multiple myeloma refractory multiple myeloma relapsed multiple myeloma B lymphoid malignancies Myeloma, Plasma-Cell Myeloma Proteins hnRNP A1 myeloma helix-destabilizing protein, mouse IgC3kappa Jir protein, human gamma 3 myeloma protein Jir, human M-proteins (Myeloma) M315 myeloma protein, mouse myeloma protein M 315, mouse McPC603 antibody myeloma protein McPC603 antibody multiple myeloma M-proteins M protein, multiple myeloma myeloma cell activator myeloma immunoglobulins myeloma immunoglobulin M603 myeloma immunoglobulin S15 myeloma protein A48, mouse A48 myeloma protein, mouse ABPC48 myeloma protein, mouse myeloma protein A 48, mouse myeloma protein Dob myeloma protein M 467 myeloma protein M467 myeloma protein MOPC 141, mouse MOPC141 myeloma protein, mouse myeloma protein MOPC 173 myeloma protein Rou IgA2 myeloma protein Rou myeloma protein TEPC15 myeloma protein T15 myeloma protein TEPC 15 myeloma protein W3129 myeloma protein WIE myeloma-associated membrane antigen KMA myeloma antigen KMA MYEOV protein, human protein 460 myeloma protein MOPC 460 TRAPPC1 protein, human multiple myeloma protein 2, human Wis heavy-chain disease protein, human myeloma protein Wis, human
Allocation: NA | Intervention model: SINGLE_GROUP
Enrollment: 7
Healthy volunteers: yes

Brief summary:
The purpose of this study is to determine whether the combination of bevacizumab and bortezomib have increased efficacy in the treatment of relapsed/ refractory multiple myeloma.

Detailed description:
Rationale: With the identification of thalidomide as an active agent in Multiple Myeloma, the role of angiogenesis in its pathogenesis has become a subject of much investigation. Micro vessel density (neovascularization) is inversely related to prognosis in Multiple Myeloma. Response to thalidomide was felt to correlate with a decline in microvessel density (Singhal et al NEJM). While the mechanism of neovascularization is yet to be fully elucidated, a number of models have shown VEGF to play a central role.

Thalidomide has been shown to synergize with a number of agents used to treat MM, including bortezomib. (Wang et al ASH 2005) This would justify the use of other therapeutics with known antiangiogenic activity in conjunction with established antimyeloma therapies.

Bortezomib, which has the precedence of known synergy with Thalidomide and has an extremely well established optimal dose, schedule, response rate, event free survival, and overall survival would make it an excellent candidate for combination therapy with other established antiangiogenic compounds.

There have been several reports of the role of VEGF in multiple myeloma. It has been shown that multiple myeloma cells secreteVEGF, which further promotes production of IL-6 in BMSCs, as well as migration and proliferation of the tumor cells. Thus VEGF is both an autocrine growth factor and trigger of IL-6-mediated paracrine multiple myeloma cell growth. Recent reports have highlighted the major role of VEGF in multiple myeloma pathogenesis, demonstrating the VEGF also increases microvessel density in the bone marrow. VEGF also inhibits dendritic cells. Taken together, these preclinical reports make strong suggestion for the promise of VEGF targeted agents in multiple myeloma (Le Gouill et al 2004).

Arms:
arm 1: Bortezomib will be administered at 1.3 mglm2 IVP on Days 1. 4, 8, and 11. Response will be assessed subsequent to each cycle. A total of 8 cycles would beplanned. Patients would be removed subsequent to Cycle 2. if progression of disease is documented.

Interventions: intervention 1: Bortezomib
Intervention descriptions: intervention 1: Bortezomib will be administered at 1.3 mglm2 IVP on Days 1. 4, 8, and 11. Response will be assessed subsequent to each cycle. A total of 8 cycles would beplanned. Patients would be removed subsequent to Cycle 2. if progression of disease is documented.

Protocol document: