Melphalan, Prednisone, Thalidomide And Bortezomib In Advanced And Refractory Multiple Myeloma Patients

Inclusion Criteria:

• Patient is of a legally consenting age as defined by local regulations.
• Patient is, in the investigator(s) opinion willing and able to comply with the protocol requirements.
• Patient has given voluntary written informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to their future medical care.
• Female patient is either post-menopausal or surgically sterilized or willing to use an acceptable method of birth control (i.e., a hormonal contraceptive, intrauterine device, diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of the study.
• Male patient agrees to use an acceptable method for contraception (i.e., condom or abstinence) for the duration of the study.
• Patient was previously diagnosed with multiple myeloma based on standard criteria.
• Patient is relapsed or refractory after one or two lines of treatment including high-dose chemotherapy with stem cell support, conventional poli-chemotherapy, thalidomide- and melphalan-based regimens.
• Patient has measurable disease, defined as follows: any quantifiable serum monoclonal protein value (generally, but not necessarily, greater than 1 g/dL of IgG M-Protein and greater than 0.5 g/dL of IgA M-Protein) and, where applicable, urine light-chain excretion of >200 mg/24 hours.
• Patient has a Karnofsky performance status ≥60%.
• Patient has a life-expectancy >3 months.
• Patient has the following laboratory values within 14 days before Baseline (day 1 of the Cycle 1, before study drug administration):
• Platelet count ≥75 x 109/L without transfusion support within 7 days before the test.
• Absolute neutrophil count (ANC) ≥ 0.75 x 109/L without the use of growth factors.
• Corrected serum calcium ≤14 mg/dL (3.5 mmol/L).
• Aspartate transaminase (AST): ≤ 2.5 x the upper limit of normal (ULN).
• Alanine transaminase (AST): ≤ 2.5 x the ULN.
• Total bilirubin: ≤ 1.5 x the ULN.
• Calculated or measured creatinine clearance: ≥20 mL/minute.

Exclusion Criteria:

• Patient has an absolute neutrophil count <0.75 × 109/L within 14 days before enrollment.
• Patient has a calculated or measured creatinine clearance <20 mL/minute within 14 days before enrollment.
• Patient has ≥Grade 2 peripheral neuropathy within 14 days before enrollment.
• Patient has known hypersensitivity to bortezomib, boron, mannitol or thalidomide.