Trial Information

A Study of Siltuximab (Anti-IL-6 Monoclonal Antibody) Effects on the QT Interval in Subjects With Monoclonal Gammopathy of Undetermined Significance, Smoldering Multiple Myeloma, or Indolent Multiple Myeloma

This is a research study with an experimental drug called siltuximab (also known as CNTO
328). Currently there are studies with siltuximab, completed or ongoing, in patients with
blood cancers such as multiple myeloma and Castleman's disease and with solid tumors such as
kidney, ovarian and prostate cancer, to see if siltuximab is safe and to determine what
effects it has on these types of cancer. This study is being done in patients with
Monoclonal Gammopathy of Undetermined Significance (MGUS), Smoldering Multiple Myeloma (SMM)
or Indolent Multiple Myeloma (IMM) to determine if siltuximab has an effect on heart
function measured by ECG recordings, and more specifically to determine if siltuximab has
any effect on the QT interval. MGUS, SMM and IMM patients usually go on to develop active
multiple myeloma which 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 the blood. The cancer cells also make proteins (called
M-proteins), which can result in damage to other organs, especially the kidneys. Siltuximab
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 will also look
to see if siltuximab may be useful in treating patients with MGUS, SMM or IMM. All
participating patients will be in the study for about 6 months and will receive siltuximab
four (4) times every 3 weeks at a dose of 15mg per kg bodyweight. Siltuximab is given as a 1
hour intravenous infusion, through a small tube that goes directly into the vein. Following
this treatment period, patients showing a response, defined as a 50% or higher reduction in
M-protein in their blood/urine, may be allowed to continue treatment with siltuximab 15mg/kg
every 4 weeks for up to 2 years.