NCT01266811

Brief Summary

The purpose of this study is to determine if there is an improvement in progression-free survival (length of time during and after treatment in which a patient is living with a disease that does not get worse) when siltuximab is added to VELCADE and dexamethasone in subjects with relapsed or refractory multiple myeloma.

Trial Health

42
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Timeline
Completed

Started Jul 2011

Shorter than P25 for phase_3 multiple-myeloma

Geographic Reach
14 countries

48 active sites

Status
withdrawn

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

December 23, 2010

Completed
1 day until next milestone

First Posted

Study publicly available on registry

December 24, 2010

Completed
6 months until next milestone

Study Start

First participant enrolled

July 1, 2011

Completed
2.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

April 1, 2014

Completed
8 months until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2014

Completed
Last Updated

January 28, 2013

Status Verified

January 1, 2013

Enrollment Period

2.8 years

First QC Date

December 23, 2010

Last Update Submit

January 25, 2013

Conditions

Keywords

dexamethasoneSiltuximabCNTO 328IL-6Monoclonal AntibodyMultiple MyelomaRelapsed or RefractoryVelcadebortezomib

Outcome Measures

Primary Outcomes (1)

  • Progression-free survival (PFS)

    Event driven, i.e. every 3-4 weeks until progression, death, or end of study (5 years after first patient is dosed)

Secondary Outcomes (5)

  • Overall survival

    Every 3 months until death or end of study (5 years after 1st patient is dosed)

  • Overall response rate

    Every 3 weeks until disease progression or end of study (5 years after 1st patient is dosed)

  • Siltuximab pharmacokinetic evaluations (Cmin, Cmax) to provide information on the pharmacokinetic profile of siltuximab

    Day 1 of Cycles 1, 2, 3, 5, 7, 11, 15, and 19 and during the follow-up period (12 weeks after last dose)

  • Dexamethasone pharmacokinetic evaluations (Cmin, AUC[t1-t2]) from approx. 30 patients from each treatment arm to provide information on the pharmacokinetic profile of dexamethasone

    Pre-dose on Day 1 of Cycles 1, 2 and 3; at Cycle 3 measured 1, 2, 4, 6 and 24 hours after dose

  • Number of adverse events as a measure of safety and tolerability

    Routinely until 30 days after last dose at a minimum, or until end of study

Study Arms (2)

001

EXPERIMENTAL

Siltuximab Velcade and dexamethasone Given in 21-day treatment cycles Siltuximab 11 mg/kg as 1 hour IV infusion on Day 1 of every cycle Velcade 1.3 mg/m2 IV push on Days 1 4 8 and 11 for Cycles 1-8 and on Days 1 and 8 for Cycles 9 and higher Dexamethasone 20 mg orally on the day of and the day after each Velcade dose

Biological: Siltuximab, Velcade and dexamethasone

002

OTHER

Placebo Velcade and dexamethasone Given in 21-day treatment cycles Placebo as 1-hour IV infusion on Day 1 of every cycle Velcade 1.3 mg/m2 IV push on Days 1 4 8 and 11 for Cycles 1-8 and on Days 1 and 8 for Cycles 9 and higher Dexamethasone 20 mg orally on the day of and the day after each Velcade dose

Drug: Placebo, Velcade and dexamethasone

Interventions

Siltuximab 11 mg/kg as 1 hour IV infusion on Day 1 of every cycle

002

Given in 21-day treatment cycles

001

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Confirmed diagnosis of multiple myeloma requiring treatment
  • Measurable secretory disease, defined as either serum M-protein \>=1 g/dL or urine M-protein (light chain) \>=¿200 mg/24 hours
  • Must have received 1 to 3 lines of prior treatment for multiple myeloma
  • Must have achieved a response (Minimal Response or better) to at least 1 prior line of treatment
  • Must have progressed on or been refractory (defined as \< Minimal Response or disease progression within 60 days of last dose) to the most recent line of treatment
  • Must not be refractory to any previous line of treatment that included a proteasome inhibitor
  • Qualifying hematology and chemistry laboratory results.

You may not qualify if:

  • Diagnosis of primary amyloidosis, plasma cell leukemia, or other conditions in which a paraprotein is present in the absence of a clonal plasma cell infiltration with lytic bone lesions
  • Grade 1 peripheral neuropathy with pain or Grade 2 or higher peripheral neuropathy
  • Allogeneic bone marrow transplantation within 28 days
  • Bone marrow transplant planned within 12 months after study start
  • Chemotherapy or radiation therapy within 21 days
  • Clinically significant infection, including known HIV or hepatitis C infection, or known hepatitis B surface antigen positivity
  • Major surgery within 21 days before or planned during the study
  • Subjects who the investigator believes would not tolerate starting doses of VELCADE or dexamethasone
  • Significant cardiac disease or myocardial infarction within 6 months
  • Vaccination with live attenuated vaccines within 4 weeks
  • Prior exposure to agents targeting IL-6 or the IL-6 receptor
  • Received any investigational agent within 30 days¿

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (48)

Unknown Facility

Iowa City, Iowa, United States

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Boston, Massachusetts, United States

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Toledo, Ohio, United States

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Willow Grove, Pennsylvania, United States

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Milwaukee, Wisconsin, United States

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Adelaide, Australia

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Camperdown, Australia

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Heidelberg, Australia

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Parkville, Australia

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Prahran, Australia

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Edegem, Belgium

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Liège, Belgium

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Turnhout, Belgium

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Yvoir, Belgium

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Plovdiv, Bulgaria

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Sofia, Bulgaria

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Varna, Bulgaria

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Toronto, Canada

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Hradec Králové, Czechia

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Liberec, Czechia

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Prague, Czechia

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Gandhinagar Guiarat, India

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Apeldoorn, Netherlands

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Deventer, Netherlands

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Zwolle, Netherlands

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Christchurch, New Zealand

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Grafton, New Zealand

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Nz 9 Takapuna Auckland, New Zealand

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Palmerston North, New Zealand

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Brzozów, Poland

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Gdansk, Poland

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Lodz, Poland

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Opole, Poland

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Wroclaw, Poland

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Hwasun Gun, South Korea

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Seoul, South Korea

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Ankara, Turkey (Türkiye)

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Bursa, Turkey (Türkiye)

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Edirne, Turkey (Türkiye)

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Cherkassy, Ukraine

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Dnipro, Ukraine

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Kharkiv, Ukraine

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Khmelnitskiy, Ukraine

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Kiev, Ukraine

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Odesa, Ukraine

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Simferopol, Ukraine

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Vinnitsa, Ukraine

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Nottingham, United Kingdom

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MeSH Terms

Conditions

Multiple MyelomaRecurrence

Interventions

BortezomibDexamethasonesiltuximab

Condition Hierarchy (Ancestors)

Neoplasms, Plasma CellNeoplasms by Histologic TypeNeoplasmsHemostatic DisordersVascular DiseasesCardiovascular DiseasesParaproteinemiasBlood Protein DisordersHematologic DiseasesHemic and Lymphatic DiseasesHemorrhagic DisordersLymphoproliferative DisordersImmunoproliferative DisordersImmune System DiseasesDisease AttributesPathologic ProcessesPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Boronic AcidsAcids, NoncarboxylicAcidsInorganic ChemicalsBoron CompoundsOrganic ChemicalsPyrazinesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsPregnadienetriolsPregnadienesPregnanesSteroidsFused-Ring CompoundsPolycyclic CompoundsSteroids, Fluorinated

Study Officials

  • Centocor, Inc. Clinical Trial

    Centocor, Inc.

    STUDY DIRECTOR
0

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

December 23, 2010

First Posted

December 24, 2010

Study Start

July 1, 2011

Primary Completion

April 1, 2014

Study Completion

December 1, 2014

Last Updated

January 28, 2013

Record last verified: 2013-01

Locations