Study of DOXIL/CAELYX (Pegylated Liposomal Doxorubicin) and VELCADE (Bortezomib) or VELCADE Monotherapy for the Treatment of Relapsed Multiple Myeloma
Study of DOXIL/CAELYX (Pegylated Liposomal Doxorubicin) and VELCADE (Bortezomib) or VELCADE Monotherapy for the Treatment of Relapsed Multiple Myeloma
The purpose of this study is to evaluate time to progression, overall survival, response rate
 and safety for the two open-label treatment groups; DOXIL/CAELYX in combination with VELCADE
 vs. VELCADE monotherapy.
This is a randomized (study drug assigned by chance), parallel-group, open-label (all
 involved people know the identity of the intervention), multicenter study in 18 countries. A
 total of 646 patients with multiple myeloma whose disease has progressed after an initial
 response to at least 1 line of prior therapy or was refractory to initial treatment will be
 enrolled. The primary endpoint is time to progression (the interval between the date of
 randomization and the date of disease progression); secondary endpoints are overall survival
 (the interval between the date of randomization and the patient's death from any cause),
 response rate (the proportion of patients in the evaluable population who achieved a complete
 or partial response), and safety. Other study endpoints include patient reported outcomes and
 exploratory pharmacogenics (to identify genetic markers of response). Patients are assessed
 for efficacy and safety every 3 weeks until disease progression is documented or for up to 42
 weeks from the start of the first dose of study drug. Patients, who do not progress after the
 42-week period, are assessed every 6 weeks until disease progression is documented. Efficacy
 evaluations includes: serum protein electrophoresis, 24-hour urine collection for protein
 electrophoresis, skeletal survey (plain films), bone marrow biopsy and aspirate, clinical or
 radiologic assessment of plasmacytomas, and serum calcium. Responses and progressions are
 assessed objectively by a computer algorithm based on the EBMT criteria. Safety evaluations
 include adverse event reports, changes in clinical laboratory findings, and tests for cardiac
 function (multiple gated acquisition scan/echocardiogram and electrocardiogram). Group A:
 VELCADE monotherapy: VELCADE 1.3 milligram per meter square (mg/m^2) to be administered by
 i.v. bolus on Days 1, 4, 8, and 11 of each 21-day cycle. Group B: DOXIL/VELCADE combination:
 treated with VELCADE at the same dose and schedule as specified in Group A. DOXIL/CAELYX 30
 mg/m^2 by intravenous infusion given on Day 4 of every 21-day cycle following the
 administration of VELCADE.
Inclusion Criteria:

 -  Patients with multiple myeloma who have received at least 1 prior therapy and who have
 either responded and later had progressive disease or have progressed during their
 first therapy (primary refractory) are eligible for the study

 -  Patients who may have received prior doxorubicin but not more than a cumulative dose
 of 240 milligram per meter square (mg/m^2) doxorubicin, DOXIL, or the equivalent
 amount of another anthracycline (i.e., 1 mg doxorubicin = 1 mg DOXIL/CAELYX = 1.8 mg
 epirubicin = 0.3 mg mitoxantrone = 0.25 mg idarubicin)

 -  Must have normal cardiac function, as evidenced by a left LVEF within institutional
 normal limits.

 Exclusion Criteria:

 -  History of treatment with VELCADE or progressive disease while receiving an
 anthracycline-containing regimen

 -  No change in disease status during initial therapy

 -  No treatment for malignancy within past 5 yrs (other than multiple myeloma) or
 progressive disease while receiving anthracycline-containing regimen

 -  Non-secretory disease

 -  Myocardial infarct within past 6 months

 -  No major surgery in past 30 days.