A Study of the Safety and Efficacy of CNTO 328 and Bortezomib to Bortezomib Alone in Patients With Relapsed or Refractory Multiple Myeloma
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
3 other identifiers
interventional
307
18 countries
80
Brief 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2 multiple-myeloma
Started Nov 2006
Longer than P75 for phase_2 multiple-myeloma
80 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
November 17, 2006
CompletedFirst Posted
Study publicly available on registry
November 22, 2006
CompletedStudy Start
First participant enrolled
November 28, 2006
CompletedPrimary Completion
Last participant's last visit for primary outcome
August 16, 2011
CompletedResults Posted
Study results publicly available
August 4, 2015
CompletedStudy Completion
Last participant's last visit for all outcomes
September 24, 2019
CompletedNovember 19, 2019
November 1, 2019
4.7 years
November 17, 2006
July 7, 2015
November 7, 2019
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Progression-free Survival
Progression-free survival was defined as the time interval between randomization and the first documented sign of disease progression (including relapse from complete response \[CR\]) by the European Bone Marrow Transplant (EBMT) criteria or death, whichever occurred first. Relapse from CR requires at least 1 of the following: Reappearance of serum or urinary M-protein on immunofixation or routine electrophoresis, confirmed by at least 1 further investigation and excluding oligoclonal immune reconstitution; Greater than or equal to (\>=) 5 percent (%) plasma cells either in a bone marrow aspirate or on trephine bone biopsy; Development of new lytic bone lesions or soft tissue plasmacytomas or definite increase in the size of residual bone lesions (development of a compression fracture does not exclude continued response and may not indicate progression); Development of hypercalcemia not attributable to any other cause.
Randomization until disease progression or death, which ever occured first (maximum up to 5 years)
Number of Participants With Adverse Events (AEs) or Serious Adverse Events (SAEs)
An AE is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; lifethreatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.
up to 5 years
Secondary Outcomes (3)
Percentage of Participants With Best Confirmed Response of Complete Response (CR) or Partial Response (PR) (Overall Response Rate)
Randomization until disease progression (maximum up to 5 years)
Percentage of Participants With Confirmed Complete Response (CR Rate)
Randomization until disease progression (maximum up to 5 years)
Overall Survival
up to 5 years
Study Arms (3)
Part 1: Siltuximab Plus Bortezomib
EXPERIMENTALSiltuximab 6 milligram per kilogram (mg/kg) will be administered as intravenous infusion once every 2 weeks along with bortezomib 1.3 milligram per square meter (mg/m\^2) during cycle 1.
Part 2: Bortezomib + Placebo
EXPERIMENTALBortezomib 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 along with matching placebo administered as intravenous infusion once every 2 weeks during 42-day treatment phase. Bortezomib 1.3 mg/m\^2 will be administered as intravenous bolus on Days 1, 8, 15, 22 followed by a 13-day rest period (cycle Days 23 to 35) along with matching placebo once every 2 weeks during 35-day Maintenance Phase. Dexamethasone tablet will be administered at first occurrence of documented disease progression or if bortezomib was discontinued due to intolerable toxicity. Dexamethasone 40 milligram per day (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.
Part 2: Bortezomib + Siltuximab
EXPERIMENTALBortezomib 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 along with Siltuximab administered as intravenous infusion once every 2 weeks during 42-day treatment phase. Bortezomib 1.3 mg/m\^2 will be administered as intravenous bolus on Days 1, 8, 15, 22 followed by a 13-day rest period (cycle Days 23 to 35) along with Siltuximab administered as intravenous infusion once every 2 weeks for 35-day Maintenance Phase. Dexamethasone tablet will be administered at 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.
Interventions
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.
Eligibility Criteria
You may qualify if:
- 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 (\> 200 mg/24 hours)
- Documented disease progression after at least 1 prior line of therapy but no more than 3 or have had no response to previous treatment (primary refractory disease)
- ECOG performance status score of less than or equal to (\<=) 2
- Adequate bone marrow, liver, and renal function
You may not qualify if:
- No prior treatment with bortezomib
- Not Refractory to high-dose dexamethasone
- Not \>= Grade 2 peripheral neuropathy
- Have not received an allogeneic bone marrow or allogeneic peripheral blood stem cell transplant
- No prior or concomitant malignancy (other than multiple myeloma) except adequately treated basal cell or squamous cell carcinoma of the skin, carcinoma in situ of the cervix, or other cancer for which the patient has been disease-free for \<= 3 years
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (80)
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Greenbrae, California, United States
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Los Angeles, California, United States
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Indianapolis, Indiana, United States
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Albuquerque, New Mexico, United States
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New York, New York, United States
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Syracuse, New York, United States
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Chapel Hill, North Carolina, United States
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North Charleston, South Carolina, United States
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Dallas, Texas, United States
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Houston, Texas, United States
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Madison, Wisconsin, United States
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Antwerp, Belgium
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B-8000 Brugge, Belgium
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Brussels, Belgium
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Edegem, Belgium
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Leuven, Belgium
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Rio de Janeiro, Brazil
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Bulgaria, Bulgaria
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Pleven, Bulgaria
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Plovdiv, Bulgaria
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Vancouver, British Columbia, Canada
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Québec, Quebec, Canada
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Calgary, Canada
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Brno, Czechia
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Hradec Králové, Czechia
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Prague, Czechia
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Grenoble, France
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Lille Cedex N/a, France
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Montpellier, France
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Pierre-Bénite, France
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Vandœuvre-lès-Nancy, France
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Aschaffenburg, Germany
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Essen, Germany
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Mainz, Germany
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Münster, Germany
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Stuttgart, Germany
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Ulm, Germany
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Athens, Greece
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Budapest, Hungary
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Debrecen, Hungary
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Gyõr, Hungary
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Nyíregyháza, Hungary
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Szeged, Hungary
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Amersfoort, Netherlands
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Amsterdam, Netherlands
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Rotterdam, Netherlands
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The Hague, Netherlands
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Bialystok, Poland
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Gdansk, Poland
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Katowice, Poland
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Lodz, Poland
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Lublin, Poland
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Poznan, Poland
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Wroclaw, Poland
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Coimbra, Portugal
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Lisbon, Portugal
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Porto, Portugal
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Baia Mare, Romania
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Brasov, Romania
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Bucharest, Romania
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Iași, Romania
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Tg Mures, Romania
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Arkhangelsk, Russia
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Izhevsk, Russia
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Moscow, Russia
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Nizhny Novgorod, Russia
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Novosibirsk, Russia
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Saint Petersburg, Russia
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Ufa, Russia
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Bratislava, Slovakia
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Martin, Slovakia
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Badalona, Spain
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Barcelona, Spain
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Madrid, Spain
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Salamanca, Spain
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Valencia, Spain
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London, United Kingdom
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Nottingham, United Kingdom
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Plymouth, United Kingdom
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Sutton, United Kingdom
Related Publications (1)
Orlowski RZ, Gercheva L, Williams C, Sutherland H, Robak T, Masszi T, Goranova-Marinova V, Dimopoulos MA, Cavenagh JD, Spicka I, Maiolino A, Suvorov A, Blade J, Samoylova O, Puchalski TA, Reddy M, Bandekar R, van de Velde H, Xie H, Rossi JF. A phase 2, randomized, double-blind, placebo-controlled study of siltuximab (anti-IL-6 mAb) and bortezomib versus bortezomib alone in patients with relapsed or refractory multiple myeloma. Am J Hematol. 2015 Jan;90(1):42-9. doi: 10.1002/ajh.23868.
PMID: 25294016DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Project Physician
- Organization
- Janssen R&D UK
Study Officials
- STUDY DIRECTOR
Janssen Research & Development, LLC Clinical Trial
Janssen Research & Development, LLC
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Who Masked
- PARTICIPANT, CARE PROVIDER
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
November 17, 2006
First Posted
November 22, 2006
Study Start
November 28, 2006
Primary Completion
August 16, 2011
Study Completion
September 24, 2019
Last Updated
November 19, 2019
Results First Posted
August 4, 2015
Record last verified: 2019-11