An Efficacy and Safety Study of Siltuximab in Participants With Relapsed or Refractory Multiple Myeloma

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Centocor, Inc.
ClinicalTrials.gov Identifier:
NCT00402181
First received: November 17, 2006
Last updated: May 13, 2014
Last verified: May 2014
  Purpose

The purpose of this study is to evaluate the safety and efficacy of siltuximab in participants with relapsed (the return of a disease or the signs and symptoms of a disease after a period of improvement.) or refractory (cancer that does not respond to treatment) multiple myeloma (a type of cancer that begins in plasma cells [white blood cells that produce antibodies]).


Condition Intervention Phase
Multiple Myeloma
Biological: Siltuximab
Drug: Dexamethasone
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 2 Multicenter Study of CNTO 328 (Anti IL-6 Monoclonal Antibody) in Subjects With Relapsed or Refractory Multiple Myeloma

Resource links provided by NLM:


Further study details as provided by Centocor, Inc.:

Primary Outcome Measures:
  • Percentage of Participants With Overall Response [ Time Frame: Baseline up to end of study (Day 807) ] [ Designated as safety issue: No ]
    The overall response is defined as percentage of participants having confirmed Complete Response (CR) and Partial Response (PR) by using the European Group for Blood and Marrow Transplantation (EBMT) criteria. CR is absence of the original monoclonal protein (M-protein) in serum and urine maintained for a minimum of 6 weeks, and disappearance of soft tissue plasmacytomas. PR is greater than or equal to (>=) 50 percent reduction in the level of the serum M-protein maintained for a minimum of 6 weeks and >= 50 percent reduction in the size of soft tissue plasmacytomas.


Secondary Outcome Measures:
  • Time to Progression (TTP) [ Time Frame: Baseline up to end of study (Day 807) ] [ Designated as safety issue: No ]
    The TTP is defined as the time interval in days between the date of first administration of study treatment (as monotherapy or as combination therapy) to the date of first documented evidence of confirmed progressive disease (including relapse from CR). CR is absence of the original M-protein in serum and urine maintained for a minimum of 6 weeks, and disappearance of soft tissue plasmacytomas.

  • Duration of Response [ Time Frame: Baseline up to end of study (Day 807) ] [ Designated as safety issue: No ]
    The duration of response is defined as the time from initial documented response (Complete Response [CR] or Partial Response [PR]), to the first documented sign of progression. CR is absence of the original M-protein in serum and urine maintained for a minimum of 6 weeks, and disappearance of soft tissue plasmacytomas. PR is >= 50% reduction in the level of the serum M-protein maintained for a minimum of 6 weeks and >= 50% reduction in the size of soft tissue plasmacytomas.

  • Number of Participants With Immune Response [ Time Frame: Day 1 (Cycle 1 [pre-dose]), treatment discontinuation, and every 3 months after the last dose (up to 3 times) ] [ Designated as safety issue: No ]
    Immune response is defined as antibody (type of protein that helps to protect the body against foreign matter, such as bacteria and viruses) response to siltuximab.

  • Percent Change From Baseline in C-Reactive Protein (CRP) Level [ Time Frame: Before siltuximab administration in Cycles 1, 2, and 3 on Days 1 and 15; thereafter, on Day 1 of each cycle up to12 cycles ] [ Designated as safety issue: No ]
    Percentage change in CRP is equal to CRP at time of measurement minus CRP at baseline divided by CRP at baseline multiplied by 100.

  • Percent Change From Baseline in C-telopeptide (CTx) Level [ Time Frame: Before siltuximab administration on Day 1 of cycles 1, 2, and 3 ] [ Designated as safety issue: No ]
    Percentage change in CTx is equal to CTx at time of measurement minus CTx at baseline divided by CTx at baseline multiplied by 100.

  • Percent Change From Baseline in N-telopeptide (NTx) Level [ Time Frame: Before siltuximab administration on Day 1 of cycles 1, 2, and 3 ] [ Designated as safety issue: No ]
    Percentage change in NTx is equal to NTx at time of measurement minus NTx at baseline divided by NTx at baseline multiplied by 100.


Enrollment: 53
Study Start Date: October 2006
Study Completion Date: July 2009
Primary Completion Date: July 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment Plan A
Siltuximab 6 milligram per kilogram (mg/kg) as intravenous (directly into the vein) infusion once every 2 weeks for 12 cycles and duration of each cycle is 28 days (if participant have complete or partial response) along with dexamethasone (starting from Cycle 2, If participant do not have complete or partial response) 40 mg tablet orally on Day 1 to 4, 9 to 12 and 17 to 20 for maximum 4 cycles after that on Day 1 to 4 up to 12 cycles.
Biological: Siltuximab
Siltuximab 6 mg/kg as intravenous infusion once every 2 weeks for 12 cycles and duration of each cycle is 28 days.
Other Name: CNTO 328
Drug: Dexamethasone
Dexamethasone 40 mg tablet orally on Day 1 to 4, 9 to 12 and 17 to 20 for maximum 4 cycles after that on Day 1 to 4 up to 12 cycles and duration of each cycle is 28 days.
Experimental: Treatment Plan B
Siltuximab 6 mg/kg as intravenous infusion once every 2 weeks along with dexamethasone 40 mg tablet orally on Day 1 to 4, 9 to 12 and 17 to 20 for maximum 4 cycles (duration of each cycle is 28 days) after that on Day 1 to 4 up to 12 cycles.
Biological: Siltuximab
Siltuximab 6 mg/kg as intravenous infusion once every 2 weeks for 12 cycles and duration of each cycle is 28 days.
Other Name: CNTO 328
Drug: Dexamethasone
Dexamethasone 40 mg tablet orally on Day 1 to 4, 9 to 12 and 17 to 20 for maximum 4 cycles after that on Day 1 to 4 up to 12 cycles and duration of each cycle is 28 days.

Detailed Description:

This is an open-label (all people know the identity of the intervention), multicenter (when more than one hospital or medical school team work on a medical research study), non-randomized (a clinical trial in which the participants are not assigned by chance to different treatment groups), prospective (study following participants forward in time) safety and efficacy study of siltuximab in participants with relapsed or refractory multiple myeloma. The study consists of 3 Phases: Screening Phase (from first visit until the first dose of study drug), Treatment Phase (from the first dose to the end-of-treatment), and Follow-up Phase (after end-of-treatment until the end of study). The duration of participation in the study for an individual participant will be up to 4 weeks for Screening Phase, approximately 52 weeks for Treatment Phase and until death, lost to follow-up, withdraw of consent or end of study, whichever, comes first for Follow-up Phase. Treatment will be administered on a 28-day cycle. The study is designed with 2 alternative treatment plans. Treatment Plan A: during first 2 cycles siltuximab will be administered alone, dexamethasone may be added to the treatment regimen based on the participant's response to treatment. Treatment Plan B: siltuximab and dexamethasone combination for the duration of the study. The first 14 eligible participants will follow Treatment Plan A and data evaluation will be conducted for participants after 2 cycles of treatment and 2 post baseline disease assessments. If at least one complete response (CR) or partial response (PR) is observed in 14 participants, all subsequent participants will follow Treatment Plan A. However, if no responses (CR or PR) are observed, all subsequent participants will follow Treatment Plan B. The primary efficacy endpoint will be percentage of participants with overall response. Participants' safety will be monitored throughout the study.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Confirmed diagnosis of multiple myeloma with relapsed or refractory disease after failing at least 2 prior lines of therapy
  • Prior treatment regimen must have included bortezomib (alone or in combination with other agents)
  • Measurable secretory disease defined as either serum monoclonal paraprotein (M- protein) greater than or equal to (>=) 1 gram per deciliter (g/dL) or urine monoclonal (light chain) protein (greater than (>) 200 milligram/24 hours)
  • Eastern Cooperative Oncology Group (ECOG) performance status score of less than or equal to (<=) 2 - Participants of childbearing potential must use adequate birth control measures, female participants of childbearing potential must have a negative serum pregnancy test at screening

Exclusion Criteria:

  • Treatment with systemic cancer therapy (including clarithromycin) or radiotherapy within 30 days before the first dose of study agent - Treatment with nitrosoureas (a group of alkylating agents used as antineoplastic drugs in the chemotherapy) within 42 days before the first dose of study agent
  • Major surgery within 30 days before the first dose of study agent or planning to have surgery (except for minor surgical procedures) during the study
  • Serious concurrent illness (medical or psychiatric), uncontrolled infection, or significant cardiac disease characterized by significant ischemic coronary disease (an imbalance between myocardial functional requirements and the capacity of the coronary vessels to supply sufficient blood flow) or congestive heart failure (condition in which the heart is unable to pump out sufficient blood to meet the metabolic need of the body) not under medical control, or any uncontrolled medical condition (for example: uncontrolled diabetes), including the presence of clinical laboratory abnormalities, that places the subject at unacceptable risk by participating in the study or confounds the ability to interpret data from the study
  • Known to be seropositive (giving a positive result in a test of blood serum) for Human Immunodeficiency Virus (HIV), or active hepatitis A, B or C infection
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00402181

Locations
United States, California
Duarte, California, United States
United States, Connecticut
Norwalk, Connecticut, United States
United States, Indiana
Indianapolis, Indiana, United States
United States, Minnesota
Rochester, Minnesota, United States
United States, New York
New York, New York, United States
United States, North Carolina
Chapel Hill, North Carolina, United States
United States, Pennsylvania
Pittsburgh, Pennsylvania, United States
United States, South Carolina
N Charleston, South Carolina, United States
United States, Texas
Houston, Texas, United States
Netherlands
Amsterdam, Netherlands
Den Haag, Netherlands
Leiden, Netherlands
Rotterdam, Netherlands
Sponsors and Collaborators
Centocor, Inc.
Investigators
Study Director: Centocor, Inc. Clinical Trial Centocor, Inc.
  More Information

Additional Information:
No publications provided

Responsible Party: Centocor, Inc.
ClinicalTrials.gov Identifier: NCT00402181     History of Changes
Other Study ID Numbers: CR012631, C0328T05, 2006-001897-26
Study First Received: November 17, 2006
Last Updated: May 13, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Centocor, Inc.:
Myeloma
Intravenous
Monoclonal antibody
Siltuximab
Dexamethasone
CNTO 328

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Dexamethasone acetate
Dexamethasone
Dexamethasone 21-phosphate
BB 1101
Antibodies, Monoclonal
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Central Nervous System Agents
Gastrointestinal Agents
Glucocorticoids
Hormones

ClinicalTrials.gov processed this record on September 30, 2014