Official Title: “An Open-Label, Randomized Study of VELCADE/Melphalan/Prednisone Versus Melphalan/Prednisone in Subjects With Previously Untreated Multiple Myeloma”

The primary reason for this study is to determine whether the addition of VELCADE (bortezomib) for injection to standard melphalan/prednisone (MP) therapy improves the time to disease progression (TTP) in subjects with previously untreated multiple myeloma.

Study Type: Interventional

Study Design: Treatment, Randomized, Open Label, Active Control, Parallel Assignment

Primary:

• Time to progression No

Secondary:

• Progression-free survival, overall response rate, overall survival, time to first response, duration of response, CR rate, and patient reported outcomes as assessed using the EORTC QLQ-C30, FACIT-F and EQ-5D instruments. No

Inclusion Criteria:

Subjects must satisfy the following criteria to be enrolled in the study:

• Male or female
• Not a candidate for HDT/SCT due to: age - subject is 65 years or older or in subjects less than 65 years of age - presence of important comorbid condition(s) likely to have a negative impact on tolerability of HDT/SCT.
• Symptomatic multiple myeloma or asymptomatic multiple myeloma with related organ or tissue damage. Asymptomatic multiple myeloma-related organ or tissue damage can include presence of asymptomatic lytic bone lesion or plasmacytoma, or presence of anemia, renal function impairment, or hypercalcemia, as long as the criteria for pre-treatment clinical laboratory values indicated below are met.
• Presence of measurable disease, defined as:
• For secretory multiple myeloma, measurable disease is defined as any quantifiable serum monoclonal protein value.
• For oligosecretory or nonsecretory multiple myeloma, measurable disease is defined by the presence of measurable soft tissue or organ (not bone) plasmacytomas as determined by clinical examination or applicable radiographs.
• Karnofsky performance status score of equal or greater then 60%.
• Willing and able to complete the PRO instruments
• Agrees to use an acceptable barrier method for contraception for the duration of the study (for male subjects); If female subjects are still having menstrual periods and are not surgically sterile, they must be practicing an effective method of birth control before entry, and throughout the study, and have a negative serum B-HCG pregnancy test at screening.
• Have pretreatment clinical laboratory values meeting the criteria as described in the protocol within 14 days before randomization.
• Subjects (or their legally acceptable representatives) must have signed an informed consent document indicating that they understand the purpose of and procedures required for the study and are willing to participate in the study.

Exclusion Criteria:

• Potential subjects who meet any of the following criteria will be excluded from participating in the study:
• Diagnosis of smoldering multiple myeloma or monoclonal gammopathy of undetermined significance (MGUS, hypercalcemia, and renal insufficiency related to the monoclonal protein; and (if determined) proportion of plasma cells in the bone marrow of 10% or less.
• Diagnosis of Waldenström's disease or other conditions in which IgM M protein is present in the absence of a clonal plasma cell infiltration with lytic bone lesions
• Prior or current systemic therapy for multiple myeloma including steroids (with the exception of emergency use of a short course [maximum of 4 days] of steroids before randomization or of prior or current use of bisphosphonates)
• Radiation therapy within 30 days before randomization
• Plasmapheresis within 30 days before randomization
• Major surgery within 30 days before randomization (kyphoplasty is not considered major surgery)
• History of allergic reaction attributable to compounds containing boron or mannitol
• Peripheral neuropathy or neuropathic pain Grade 2 or higher.
• Uncontrolled or severe cardiovascular disease, including myocardial infarction, within 6 months of enrollment, uncontrolled angina, clinically significant pericardial disease, or cardiac amyloidosis
• Other malignancy within the past 5 years. Exceptions if treated and not active include the following: basal cell or nonmetastatic squamous cell carcinoma of the skin, cervical carcinoma in situ or International Federation of Gynecology and Obstetrics (FIGO) Stage 1 carcinoma of the cervix
• Concurrent medical condition or disease (e.g., active systemic infection, uncontrolled diabetes) that is likely to interfere with study procedures or results, or that, in the opinion of the investigator would constitute a hazard for participating in this study
• Use of any investigational drugs within 30 days before randomization
• Employees of the investigator or study center, with direct involvement in the proposed study or other studies under the direction of that investigator or study center, or family members of the employees or the investigator.

Lead Sponsor: Millennium Pharmaceuticals

Investigative Clinical Research of Indiana, LLC

Indianapolis Indiana 46254 United States

Information obtained from ClinicalTrials.gov on July 18, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00111319

Study ID Number: 26866138-MMY-3002

ClinicalTrials.gov Identifier: NCT00111319

Health Authority: United States: Food and Drug Administration