Melphalan, Prednisone, Thalidomide And Bortezomib In Advanced And Refractory Multiple Myeloma Patients
Melphalan, Prednisone, Thalidomide And Bortezomib In Advanced And Refractory Multiple Myeloma Patients
The purpose of this study is to evaluate the safety and the efficacy of the association of
 Melphalan/Prednisone/Thalidomide/VELCADE (MPTV) as salvage treatment in advanced and
 refractory myeloma patients. This association might further increase the response rate
 achieved by the standard oral MP regimen.
In Multiple Myeloma (MM) patients, the conventional treatment is the oral combination
 melphalan and prednisone (MP). thalidomide has been widely used in myeloma, it has been
 proved clinical effective in refractory myeloma patients, it acts sinergistically in
 association with dexamethasone. In newly diagnosed patients, the combination oral MP plus
 thalidomide increased the partial and complete response rate.Bortezomib represents a novel
 class of anti-cancer drugs, it is active in patient with multiple myeloma who are refractory
 to conventional chemotherapy. In a preliminary report, the combination of VELCADE and
 Thalidomide induced a remarkable 60% PR rate in advanced refractory myeloma patients. This
 study will evaluate the safety and the efficacy of the association of Melphalan/
 Prednisone/Thalidomide/VELCADE (MPTV) as salvage treatment in advanced and refractory myeloma
 patients. This association might further increase the response rate achieved by the standard
 oral MP regimen.
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 consent may be withdrawn by the patient at any time without prejudice to their future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.