Clinical trial NCT00048230 (phase 3, status: completed)
Conditions: multiple myeloma
ICD codes: C90.01, C90.02, C90.00
Drugs: bortezomib
SMILES: ClCCN(CCCl)P1(=O)NCCCO1
Eligibility criteria:

        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             consent may be withdrawn by the patient at any time without prejudice to their future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, intra-uterine
             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 for the duration of
             the study.

          -  Patient was previously diagnosed with multiple myeloma based on standard criteria and
             currently requires second-, third-, or fourth-line therapy because of PD, defined as a
             25% increase in M-protein, development of new or worsening of existing lytic bone
             lesions or soft tissue plasmacytomas, or hypercalcemia (serum calcium >11.5 mg/dL), or
             relapse from CR.

          -  Patient has measurable disease, defined as follows:

          -  For secretory multiple myeloma, measurable disease is defined as any quantifiable
             serum monoclonal protein value (generally, but not exclusively, greater than 1 g/dL of
             IgG M-Protein and greater than 0.5g/dL IgA) and, where applicable, urine light-chain
             excretion of ≥200 mg/24 hours.

          -  For oligo- 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 assessments. Therefore, other disease sites (bone
             marrow; extramedullary mass) must be assessed and followed. In patients with
             non-secretory multiple myeloma, there is no M-protein in serum or urine by
             immunofixation.

          -  Patient has a Karnofsky performance status ≥60%.

          -  Patient has a life-expectancy >3 months.

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

          -  Platelet count ≥50 x 10E+9/L without transfusion support within 7 days before the
             laboratory test.

          -  Hemoglobin ≥7.5 g/dL, without transfusion support within 7 days before the laboratory
             test.

          -  Absolute neutrophil count (ANC) ≥0.75 x 10E+9/L without the use of colony stimulating
             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 (ALT): ≤2.5 x the ULN.

          -  Total bilirubin: ≤1.5 x the ULN.

          -  Calculated or measured creatinine clearance: ≥20 mL/minute.

        Exclusion Criteria

          -  Patient previously received treatment with VELCADE.

          -  Patient previously was refractory to treatment with high-dose dexamethasone, as
             experiencing less than a partial response to or PD within 6 months after discontinuing
             dexamethasone, or discontinued dexamethasone because of ≥Grade 3 dexamethasone-related
             toxicity.

          -  Previous high-dose dexamethasone therapy is defined as >500 mg dexamethasone or
             equivalent over a 10-week period, whether administered alone or as part of the VAD
             regimen.

          -  Patient received nitrosoureas within 6 weeks or any other chemotherapy, including
             thalidomide or clarithromycin, or radiation therapy within 3 weeks before enrollment.

          -  Patient received corticosteroids (>10 mg/day prednisone or equivalent) within 3 weeks
             before enrollment.

          -  Patient received immunotherapy or antibody therapy within 8 weeks before enrollment.

          -  Patient received plasmapheresis within 4 weeks before enrollment.

          -  Patient had major surgery within 4 weeks before enrollment. (Kyphoplasty is not
             considered major surgery.)

          -  Patient has a history of allergic reaction attributable to compounds containing boron
             or mannitol.

          -  Patient has peripheral neuropathy of Grade 2 or greater intensity, as defined by the
             NCI Common Toxicity Criteria (NCI CTC):

          -  Grade 2: Objective sensory loss or paresthesia (including tingling), interfering with
             function, but not interfering with activities of daily living (ADLs).

          -  Grade 3: Sensory loss or paresthesia interfering with ADLs.

          -  Grade 4: Permanent sensory loss that interferes with function.

          -  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 was treated for a cancer other than multiple myeloma within 5 years before
             enrollment, with the exception of basal cell carcinoma or cervical cancer in situ.

          -  Patient has cardiac amyloidosis.

          -  Patient has poorly controlled hypertension, diabetes mellitus, or other serious
             medical or psychiatric illness that could potentially interfere with the completion of
             treatment according to this protocol.

          -  Patient is known to be human immunodeficiency virus (HIV)-positive. (Patients assessed
             by the investigator to be at risk for HIV infection should be tested in accordance
             with local regulations.)

          -  Patient is known to be hepatitis B surface antigen-positive or has known active
             hepatitis C infection.

          -  Patient has an active systemic infection requiring treatment.

          -  Female patient is pregnant or breast-feeding.

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