A Study of the Safety and Efficacy of CNTO 328 and Bortezomib to Bortezomib Alone in Patients With Relapsed or Refractory Multiple Myeloma
Condition: Multiple Myeloma
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell
Study type: Interventional
Phase: Phase 2

Summary: 
      The purpose of Part 1 of the study is to determine the safety of the combination of
      Siltuximab (CNTO 328) and bortezomib (Velcade). The purpose of Part 2 of the study is to
      compare the length of progression free survival for those patients given CNTO 328 and
      bortezomib to those patients given bortezomib alone.
    

Detailed description: 
      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.
    

Intervention name(s): Siltuximab; Bortezomib; Placebo; Dexamethasone
Intervention type(s): Biological; Drug; Drug; Drug
Intervention description(s): Siltuximab 6 mg/kg will be administered as intravenous infusion once every 2 weeks during cycle 1 in Part 1. Siltuximab 6 mg/kg will be administered as intravenous infusion once every 2 weeks during 42-day Treatment Phase and 35-day Maintenance Phase in Part 2.; Bortezomib 1.3 mg/m^2 will be administered as intravenous bolus once every 2 weeks during cycle 1 in Part 1. Bortezomib 1.3 mg/m^2 will be administered as intravenous bolus on Days 1, 4, 8, 11, followed by a 10-day rest period; and on Days 22, 25, 29, and 32 followed by a 10-day rest period during 42-day treatment phase in Part 2. Bortezomib 1.3 mg/m2 will be administered as intravenous bolus on Days 1, 8, 15, 22 followed by a 13-day rest period (cycle Days 23 to 35) during 35-day Maintenance Phase in Part 2.; Matching placebo will be administered as intravenous infusion once every 2 weeks during 42-day treatment phase and 35-day maintenance phase in Part 2.; Dexamethasone tablet will be administered in this study at the first occurrence of documented disease progression or if bortezomib was discontinued due to intolerable toxicity. Dexamethasone 40 mg/day will be administered on days 1-4, 9-12, and 17-20 for four 28-day cycles then 40 mg/day for Days 1-4 for all subsequent cycles in treatment phase and maintenance phase of Part 2.
Other intervention name(s): CNTO 328; VELCADE
Intervention MeSH terms: Dexamethasone; Bortezomib; Siltuximab
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Care Provider)
Primary purpose: Treatment
Keywords: multiple myeloma; Monoclonal Antibody; Intravenous; refractory or relapsed multiple myeloma; velcade; bortezomib