Bendamustine, Wkly Bortezomib, Lenalidomide and Dexamethasone for Multiple Myeloma

An Open-Label Phase I/II Study of Bendamustine, Weekly Bortezomib, Lenalidomide and Dexamethasone for the Treatment of Relapsed or Refractory Multiple Myeloma

The purpose of the study is to determine the safety and efficacy of the use of bendamustine in combination with a commonly used combination chemotherapy to treat relapsed and refractory multiple myeloma. The study will be conducted in two phases. Participants in phase I will receive 1 of 4 escalating doses of bendamustine. Once the maximum tolerated dose of bendamustine is determined, phase II of this trial will begin. Participants in phase II will receive the maximum tolerated dose of bendamustine in combination with standard of care chemotherapy.

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, most patients will relapse and a cure remains an elusive goal.

Inclusion Criteria:

• Adults with relapsed and/or refractory myeloma who have received between 1-4 prior lines of therapy
• Must have adequate liver and renal function
• Zubrod Performance Status (ZPS) of 2 or better
• Must have measurable disease

Exclusion Criteria:

• Peripheral neuropathy of grade II or higher
• Thrombocytopenia (platelets less than 50,000/uL)
• Neutropenia (ANC<1000/uL)
• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >2.4 X ULN
• Total bilirubin >1.5 X upper limit of normal (ULN)
• Creatinine clearance of less than 45 milliliters per minute (mL/min)
• Patients with HIV
• Patients with active hepatitis
• Pregnant or lactating women
• Individuals of child-bearing potential not using adequate contraception
• Individuals unable to provide informed consent