Bendamustine, Wkly Bortezomib, Lenalidomide and Dexamethasone for Multiple Myeloma (BVRD)

• Maximally Tolerated Dose of Bendamustine [ Time Frame: 21 days ] [ Designated as safety issue: Yes ]
  Primary objective of this phase is to determine the MTD of bendamustine when combined with bortezomib, lenalidomide and dexamethasone in subjects with relapsed and/or refractory multiple myeloma.
  
  

• Drug Toxicity [ Time Frame: 21 days ] [ Designated as safety issue: Yes ]

  toxicity is defined as the inability to complete cycle 1 due to the following: Grade 3 or higher non-hematologic toxicity that are clearly not related to disease progression or intercurrent illness

  • nausea, vomiting, diarrhea,
  • Grade 3 or 4 venous thromboembolic events
  • Grade 4 hematologic toxicity defined as: thrombocytopenia with platelets less than or equal to 10,000 on more than one occasion despite transfusion support
  
  
• Survival [ Time Frame: 168 days ] [ Designated as safety issue: Yes ]
  The secondary objectives of the phase II portion of this study are to identify Median Progression-free survival, Median Overall Survival, Median Time to Next Treatment, and to identify any prognostic features that correlate to improved response.
  
  
• Response Rates [ Time Frame: 168 days ] [ Designated as safety issue: Yes ]
  The primary objective of the phase II portion of this study is to determine the overall response rate (Minor Response (MR), partial response (PR), very good partial response (VGPR), complete response (CR), and stringent complete response (SCR) in patients treated with bendamustine in combination with weekly bortezomib, plus lenalidomide and dexamethasone. ORR will be calculated as the percentage of patients who achieve a MR or better after up to 8 cycles of protocol therapy.
  
  

Multiple myeloma is a multi-organ neoplastic disorder caused by the clonal proliferation of plasma cells. It has an incidence of about 4.5/100,000 per year in the U.S., making it the second most common hematologic malignancy. For many years, alkylating agents have been the backbone of treatment. The combination of melphalan and prednisone was, for many years, the standard of care for patients who were not candidates for autologous transplantation. Melphalan continues to be the primary conditioning agent for autologous transplant,and cyclophosphamide has also gained a foothold in the treatment of this disease.

The introduction of novel agents has fundamentally changed the landscape of treating this disease, although the true effects on survival are not yet known. Immunomodulatory agents and proteosome inhibitors, including thalidomide, lenalidomide and bortezomib, have been used in both newly diagnosed and relapsed patients. Currently, there is intense clinical research on the optimal way to combine these novel agents with the traditional backbones of treatment - including alkylators, with one another and, eventually, with the subsequent iterations of these classes of drugs. However, despite the therapeutic excitement surrounding this disease, nearly all patients will relapse, and cure remains an elusive goal for all but a rare handful.