Trial Information

A Phase 2, Randomized, Double-blind, Placebo-controlled Study Comparing the Combination of CNTO 328 (Anti-IL-6 Monoclonal Antibody) and Velcade� Versus Velcade Alone in Subjects With Relapsed or Refractory Multiple Myeloma

The purpose of this study is to see what effects CNTO 328 has on relapsed or refractory
multiple myeloma. The study drug, CNTO 328, is a chimeric (part mouse) antibody (small
protein that is important for fighting infection).CNTO 328 blocks a small protein called
Interleukin 6 (IL-6). IL-6 is made naturally by your body, and at normal levels is
important for inflammatory response. High levels of IL-6 can help cancer cells grow and
interfere with chemotherapy drugs killing cancer cells. Cancer-related sickness such as
cachexia (weight loss), bone resorption (weakening of your bones), and depression have been
linked to high levels of IL-6. CNTO 328 has been shown to slow down tumor growth or shrink
tumors when tested in animals. In other clinical trials, over 100 patients have received
CNTO 328. There are studies ongoing in participants with kidney cancer, hematologic
malignancies (blood cancers such as multiple myeloma), and prostate cancer, to see if CNTO
328 is safe and to see what effects it has on these types of cancer. At this time, it is
unknown what effect CNTO 328 has had on the participants' cancer. Bortezomib is a type of
drug known as a "proteasome inhibitor." A proteasome is a substance that is found in every
cell and it is there to help to break down other substances ('proteins') and has a role in
the way cells divide. If the proteasome is inhibited, it cannot perform its function in the
cell, and if a cell cannot divide it dies. Over 8000 patients with multiple myeloma and
other types of cancer have been treated with bortezomib. Bortezomib has been extensively
studied in patients with previously treated multiple myeloma. Based on its established
activity in pretreated multiple myeloma, bortezomib is registered in the United States and
in Europe for the treatment of multiple myeloma patients who have received at least two
prior therapies and have demonstrated disease progression on the last therapy. Bortezomib
is currently also being studied in several other cancer types.This study consists of two
parts. The purpose of Part 1 is to determine the safety of CNTO 328 and bortezomib when
given together as a treatment. The purpose of Part 2 is to compare the safety and effects
(good and bad) of the combination of CNTO 328 and bortezomib to the safety and effects of
bortezomib alone. About 20 patients will take part in the first part of the study. About
270 patients will take part in the second part of the study at approximately 70 sites in the
US, Canada, and Europe. Patients will be in the study for about 12 months, with a follow-up
period of around 9 months. The study is divided into four different phases: Screening
phase-which lasts up to 4 weeks. During this phase the study doctor will perform tests to
see if the patient can participate in the study.Treatment phase-which may last up to 4
cycles of 42 days each during which the patient will be treated with CNTO 328 and
bortezomib. Maintenance phase-If the patient benefits from the therapy in the treatment
phase, the patient will continue to receive CNTO 328 and bortezomib, but now in cycles of 35
days each. Follow up phase, this includes an end of treatment visit 4 weeks after the
patient's last infusion and follow up visits every three months until the patient starts a
new anti-cancer treatment. CNTO 328 6mg/kg ( 6 milligrams per kilogram of body weight) will
be given intravenously (into the vein) over 2 hours once every 2 weeks. Patients who
respond with stable disease or better may receive additional doses. Bortezomib will be given
IV (into the vein) at 1.3 mg/m2 over 3-5 seconds twice a week for 2 weeks followed by 1 week
of rest.