A Study of the Safety and Effectiveness of CNTO 328 When Added to Velcade-Melphalan-Prednisone in Patients With Multiple Myeloma

This is a research study with a new investigational drug called CNTO328. CNTO328 is being
developed to see if it may be useful in treating Multiple Myeloma (MM). Multiple Myeloma
(MM), is a type of cancer that affects the blood and bone marrow. The cancer cells in the
bone marrow can cause the normal bone marrow cells to breakdown. This can result in low
levels of red blood cells (which may make the patient feel tired or fatigued), low levels of
white blood cells (which may increase the patient's chances of infections) or low levels of
platelets (which may increase risk of bleeding). The cancer cells can cause damage to the
normal bone. This can cause bone pain, bone fractures, and can increase the level of calcium
in your blood. The cancer cells also make proteins, which can result in damage to other
organs, especially the kidneys. The study drug, CNTO 328, is a chimeric (part mouse and
part human) antibody (immunoglobulin that is important for fighting infection). It does
this by blocking another small protein called Interleukin 6 (IL-6). The body makes IL-6
naturally, and at normal levels it is important for the inflammatory response. But high
levels of IL-6 can help cancer cells grow and interfere with chemotherapy drugs killing
cancer cells. Cancer-related sicknesses such as weight loss, bone weakening, and depression
have been linked to high levels of IL-6. This study tests the safety and effectiveness of
CNTO 328 when it is taken together with VMP (Velcade, melphalan, and prednisone). There
are 2 parts to this study. In Part One, the purpose is to study the safety of CNTO 328 in
combination with VMP and all patients will be treated with CNTO 328 plus VMP. About 12
patients will participate in Part one of the study. In Part 2, the purpose of Part 2 is to
study the effectiveness (measured by EBMT criteria) and safety of CNTO 328 in combination
with VMP compared with the effectiveness and safety of VMP alone. In part 2 , there are two
treatment groups, Group A and Group B. To try to make sure the groups are similar, patients
will be put into Group A or Group B, randomly (by chance), like flipping a coin. Patients
in Group A will receive CNTO 328 plus VMP. Patients in Group B will receive just VMP.
About 104 patients will participate in Part two of the study. Velcade (V), also known as
Bortezomib, is injected directly into the vein all at once. This is called an IV bolus
injection. CNTO 328 is given through a small tube that goes directly into the vein.
Melphalan and Prednisone (M, P) are given orally. The treatment period may last up to 54
weeks and is divided into cycles lasting about 6 weeks. Patients who are in Part 2, Group B
may be eligible to receive up to 1 additional year of CNTO 328. Safety assessments will be
performed throughout the study and include obtaining and evaluating laboratory tests, vital
signs (e.g., blood pressure), and the occurrence and severity of adverse events. CNTO 328
plus VMP will be given in 42 day treatment cycles (up to 9 cycles). CNTO 328 11mg/kg or 8.3
mg/kg will be given on Days 1 and 22. Velcade 1.3 mg/m2 will be given on Day 1, 4, 8, 11,
22, 25, 29 and 32 for Cycles 1-4 and on days 1, 8, 22 and 29 of Cycles 5-9. Melphalan
9mg/kg and prednisone 60mg/kg will be given on Days 1-4 of each cycle.