VELCADEXA: Velcade and Dexamethasone in Multiple Myeloma
VELCADEXA: Velcade and Dexamethasone in Multiple Myeloma
The primary efficacy objective of this study is to study the efficacy in terms of response
 rate to alternating bortezomib/dexamethasone regimen
Multiple Myeloma is a plasma cell disorder characterized by an uncontrolled proliferation of
 bone marrow plasma cells leading to skeletal destruction with bone pain, anemia, renal
 failure, hypercalcemia, recurrent bacterial infections and extramedullary plasmacytomas. It
 accounts for 1% of all malignancies and slightly more than 10% of hematologic malignancies,
 with an annual incidence of about four per 100.000. Although this disease is incurable with a
 median survival of about 3 years, remarkable treatment advances have been recently made,
 including high-dose therapy followed by stem cell rescue and, particularly, the introduction
 of novel promising agents with new mechanisms of action.

 Data from pre-clinical and clinical studies conducted to date support the continued
 development of VELCADE for the treatment of Multiple Myeloma. Standard chemotherapy remains
 as the gold standard for induction before HDT/SCT treatment in younger multiple myeloma
 patients (<65 years). Since VELCADE has a mechanism of action different from chemotherapy and
 dexamethasone and is considered to be efficacious in Multiple Myeloma, its introduction in
 induction regimens may contribute to increase the response rate and eventually survival of
 these patients that represent half of myeloma population.

 Since VBMCP/VBAD is considered to be the gold standard for Multiple Myeloma patients <65
 years as induction regimen prior HDT/SCT, the results of VEL/DEX will be compared with those
 obtained in 100 patients treated with VBMCP/VBAD chemotherapy in our last GEM protocol
 (Spanish Myeloma Group) for patients <65 years (closed in Dec 2004
Inclusion Criteria:

 -  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 consent may be withdrawn by the patient at any time without prejudice to their future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.

 -  Age over 18 and under 65 years old.

 -  Patient recently diagnosed with symptomatic Multiple Myeloma based on standard
 criteria and that has not received any previous chemotherapy treatment for Multiple
 Myeloma.

 -  Patient has measurable disease, defined as follows:

 For secretory multiple myeloma, measurable disease is defined as any quantifiable serum
 monoclonal protein value and, where applicable, urine light-chain excretion of ≥ 200 mg/24
 hours.

 For poor or non-secretory multiple myeloma, measurable disease is defined by the presence
 of soft tissue (not bone) plasmacytomas as determined by clinical examination or applicable
 radiographs (i.e. MRI, CT-Scan). In patients with oligosecretory multiple myeloma, the
 serum and/or urine M-protein measurements are very low and difficult to follow for response
 assessment. In patients with non-secretory multiple myeloma, there is no M-protein in serum
 or urine by immunofixation.

 -  Patient has a ECOG performance status < 2.

 -  Patient has a life-expectancy >3 months.

 -  Patient has the following laboratory values within 14 days before Baseline visit (Day
 1 of Cycle 1, before study drug administration):

 Platelet count ≥ 50x109/L, hemoglobin ≥ 8 g/dl and absolute neutrophil count (ANC) ≥
 1.0x109/L; Corrected serum calcium <14mg/dl. Aspartate transaminase (AST): ≤ 2.5 x the
 upper limit of normal. Alanine transaminase (ALT): ): ≤ 2.5 x the upper limit of normal.
 Total bilirubin: ≤1.5 x the upper limit of normal. Serum creatinine value ≤ 2mg/dl

 Exclusion Criteria:

 -  Patient previously received treatment with VELCADE.

 -  Patient previously received treatment for Multiple Myeloma

 -  Patient had major surgery within 4 weeks before enrollment.

 -  Patient has a platelet count < 50x 109/L within 14 days before enrollment.

 -  Patient has an absolute neutrophil count < 1.0 x 109/L within 14 days before
 enrollment.

 -  Patient has < Grade 2 peripheral neuropathy within 14 days before enrollment.

 -  Patient has hypersensitivity to bortezomib, boron or mannitol.

 -  Patient has received other investigational drugs within 14 days before enrollment.

 -  Patient is known to be seropositive for the human immunodeficiency virus (HIV),
 Hepatitis B surface antigen-positive or active hepatitis C infection.

 -  Patient had a myocardial infarction within 6 months of enrollment or has New York
 Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe
 uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute
 ischemia or active conduction system abnormalities.

 -  Patient is enrolled in another clinical research study and/or is receiving an
 investigational agent for any reason.

 -  Pregnancy, breast-feeding or fertile women who are not going to use a medical
 effective contraceptive method during the trial.