- ICH GCP
- US Clinical Trials Registry
- Klinisk forsøg NCT01266811
A Phase 3 Study of Siltuximab or Placebo in Combination With Velcade and Dexamethasone in Patients With Relapsed or Refractory Multiple Myeloma
25. januar 2013 opdateret af: Centocor, Inc.
A Phase 3, Randomized, Double-blind Study of Siltuximab (Anti-IL-6 Monoclonal Antibody) or Placebo in Combination With VELCADE and Dexamethasone for the Treatment of Subjects With Relapsed or Refractory Multiple Myeloma
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.
Studieoversigt
Status
Trukket tilbage
Betingelser
Intervention / Behandling
Detaljeret beskrivelse
This is a research study with an experimental drug called siltuximab (also known as CNTO 328).
Siltuximab is being developed to see if it may be useful in treating multiple myeloma, including multiple myeloma that has returned after (relapsed) or did not respond (refractory) to previous treatment.
Multiple myeloma is a type of cancer that affects the blood and bone marrow.
The cancer cells in the bone marrow can cause the normal bone marrow cells to breakdown.
This can result in low levels of red blood cells (which may make the patient feel tired or fatigued), low levels of white blood cells (which may increase the patient's chances of infections) or low levels of platelets (which may increase risk of bleeding).
The cancer cells can cause damage to the normal bone.
This can cause bone pain, bone fractures, and can increase the level of calcium in the blood.
The cancer cells also make proteins (called M-proteins), which can result in damage to other organs, especially the kidneys.
Siltuximab is a chimeric (part mouse and part human) antibody (immunoglobulin that is important for fighting infection).
Siltuximab blocks another small protein called Interleukin 6 (IL-6).
The body makes IL-6 naturally, and at normal levels it is important for the inflammatory response.
But high levels of IL-6 can help cancer cells grow and interfere with chemotherapy drugs killing cancer cells.
Cancer-related sicknesses such as weight loss, bone weakening, and depression have been linked to high levels of IL-6.
This study tests the effectiveness and safety of siltuximab when it is taken together with Velcade and dexamethasone.
There are two treatment groups, Arm A and Arm B. To try to make sure the groups are similar, patients will be put into Arm A or Arm B, randomly (by chance), like flipping a coin.
Patients in Arm A will receive siltuximab plus Velcade and dexamethasone.
Patients in Arm B will receive placebo plus Velcade and dexamethasone.
About 500 patients will participate in the study.
Velcade, also known as bortezomib, is injected directly into the vein all at once.
This is called an intravenous (IV) push.
Siltuximab or placebo is given as a 1 hour IV infusion through a small tube that goes directly into the vein.
Dexamethasone is given orally.
The treatment period is divided into cycles lasting about 21 days which will last until the patient's multiple myeloma gets worse, side effects that are not acceptable happen or when the patient decides to withdraw consent for treatment, whichever occurs first.
Siltuximab 11mg/kg or placebo will be given on Day 1 of every cycle.
Velcade 1.3 mg/m2 will be given 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 will be given on the day of and the day after each Velcade dose.
Safety assessments will be performed throughout the study and include obtaining and evaluating laboratory tests, vital signs (e.g.
blood pressure), and checking the occurrence and severity of adverse events.
Disease assessments will also be performed and include obtaining and evaluating blood and 24 hour urine samples, bone marrow aspirate and/or biopsy samples and clinical and radiologic evaluations.
After treatment, patients will enter the follow-up period, which includes visits up to 12 weeks after the last dose and checks every three months until death or the end of the study.
Patients who stop treatment before their multiple myeloma gets worse will have disease assessments until their disease gets worse, they start a new multiple myeloma treatment, they decide to withdraw consent for study participation or the end of the study, whichever happens first.
Siltuximab or placebo plus Velcade and dexamethasone will be given in 21-day treatment cycles until worsening of disease (progression), unacceptable toxicity or withdrawal of consent for treatment, whichever comes first.
Siltuximab 11 mg/kg or placebo will be given on Day 1 of every cycle.
Velcade 1.3 mg/m2 will be given 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 will be given on the day of and the day after each Velcade dose.
Undersøgelsestype
Interventionel
Fase
- Fase 3
Kontakter og lokationer
Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.
Studiesteder
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Adelaide, Australien
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Camperdown, Australien
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Heidelberg, Australien
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Parkville, Australien
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Prahran, Australien
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Edegem, Belgien
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Liège, Belgien
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Turnhout, Belgien
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Yvoir, Belgien
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Plovdiv N/A, Bulgarien
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Sofia, Bulgarien
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Varna, Bulgarien
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Toronto, Canada
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Nottingham, Det Forenede Kongerige
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Iowa
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Iowa City, Iowa, Forenede Stater
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Massachusetts
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Boston, Massachusetts, Forenede Stater
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Ohio
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Toledo, Ohio, Forenede Stater
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Pennsylvania
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Willow Grove, Pennsylvania, Forenede Stater
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Wisconsin
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Milwaukee, Wisconsin, Forenede Stater
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Apeldoorn, Holland
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Deventer, Holland
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Zwolle, Holland
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Gandhinagar Guiarat, Indien
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Ankara, Kalkun
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Bursa, Kalkun
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Edirne, Kalkun
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Hwasun Gun, Korea, Republikken
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Seoul, Korea, Republikken
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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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Brzozow, Polen
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Gdansk, Polen
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Lodz, Polen
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Opole, Polen
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Wroclaw, Polen
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Hradec Kralove, Tjekkiet
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Liberec, Tjekkiet
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Praha, Tjekkiet
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Praha 2, Tjekkiet
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Cherkassy, Ukraine
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Dnepropetrovsk, Ukraine
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Kharkov, Ukraine
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Khmelnitskiy, Ukraine
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Kiev, Ukraine
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Odessa, Ukraine
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Simferopol, Ukraine
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Vinnitsa, Ukraine
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Deltagelseskriterier
Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.
Berettigelseskriterier
Aldre berettiget til at studere
18 år og ældre (Voksen, Ældre voksen)
Tager imod sunde frivillige
Ingen
Køn, der er berettiget til at studere
Alle
Beskrivelse
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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¿
Studieplan
Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
- Primært formål: Behandling
- Tildeling: Randomiseret
- Interventionel model: Parallel tildeling
- Maskning: Firedobbelt
Våben og indgreb
Deltagergruppe / Arm |
Intervention / Behandling |
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Eksperimentel: 001
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
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Given in 21-day treatment cycles
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Andet: 002
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
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Siltuximab 11 mg/kg as 1 hour IV infusion on Day 1 of every cycle
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Hvad måler undersøgelsen?
Primære resultatmål
Resultatmål |
Tidsramme |
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Progression-free survival (PFS)
Tidsramme: Event driven, i.e. every 3-4 weeks until progression, death, or end of study (5 years after first patient is dosed)
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Event driven, i.e. every 3-4 weeks until progression, death, or end of study (5 years after first patient is dosed)
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Sekundære resultatmål
Resultatmål |
Tidsramme |
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Overall survival
Tidsramme: Every 3 months until death or end of study (5 years after 1st patient is dosed)
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Every 3 months until death or end of study (5 years after 1st patient is dosed)
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Overall response rate
Tidsramme: Every 3 weeks until disease progression or end of study (5 years after 1st patient is dosed)
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Every 3 weeks until disease progression or end of study (5 years after 1st patient is dosed)
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Siltuximab pharmacokinetic evaluations (Cmin, Cmax) to provide information on the pharmacokinetic profile of siltuximab
Tidsramme: Day 1 of Cycles 1, 2, 3, 5, 7, 11, 15, and 19 and during the follow-up period (12 weeks after last dose)
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Day 1 of Cycles 1, 2, 3, 5, 7, 11, 15, and 19 and during the follow-up period (12 weeks after last dose)
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Dexamethasone pharmacokinetic evaluations (Cmin, AUC[t1-t2]) from approx. 30 patients from each treatment arm to provide information on the pharmacokinetic profile of dexamethasone
Tidsramme: Pre-dose on Day 1 of Cycles 1, 2 and 3; at Cycle 3 measured 1, 2, 4, 6 and 24 hours after dose
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Pre-dose on Day 1 of Cycles 1, 2 and 3; at Cycle 3 measured 1, 2, 4, 6 and 24 hours after dose
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Number of adverse events as a measure of safety and tolerability
Tidsramme: Routinely until 30 days after last dose at a minimum, or until end of study
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Routinely until 30 days after last dose at a minimum, or until end of study
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Samarbejdspartnere og efterforskere
Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.
Sponsor
Datoer for undersøgelser
Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.
Studer store datoer
Studiestart
1. juli 2011
Primær færdiggørelse (Forventet)
1. april 2014
Studieafslutning (Forventet)
1. december 2014
Datoer for studieregistrering
Først indsendt
23. december 2010
Først indsendt, der opfyldte QC-kriterier
23. december 2010
Først opslået (Skøn)
24. december 2010
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Skøn)
28. januar 2013
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
25. januar 2013
Sidst verificeret
1. januar 2013
Mere information
Begreber relateret til denne undersøgelse
Nøgleord
Yderligere relevante MeSH-vilkår
- Hjerte-kar-sygdomme
- Karsygdomme
- Sygdomme i immunsystemet
- Neoplasmer efter histologisk type
- Neoplasmer
- Lymfoproliferative lidelser
- Immunproliferative lidelser
- Hæmatologiske sygdomme
- Hæmoragiske lidelser
- Hæmostatiske lidelser
- Paraproteinæmier
- Blodproteinforstyrrelser
- Myelomatose
- Neoplasmer, Plasmacelle
- Lægemidlers fysiologiske virkninger
- Molekylære mekanismer for farmakologisk virkning
- Autonome agenter
- Agenter fra det perifere nervesystem
- Enzymhæmmere
- Anti-inflammatoriske midler
- Antineoplastiske midler
- Antiemetika
- Gastrointestinale midler
- Glukokortikoider
- Hormoner
- Hormoner, hormonsubstitutter og hormonantagonister
- Antineoplastiske midler, hormonelle
- Proteasehæmmere
- Dexamethason
- Dexamethasonacetat
- BB 1101
- Bortezomib
- Siltuximab
Andre undersøgelses-id-numre
- CR017743
- CNTO328MMY3001 (Anden identifikator: Centocor, Inc.)
Disse oplysninger blev hentet direkte fra webstedet clinicaltrials.gov uden ændringer. Hvis du har nogen anmodninger om at ændre, fjerne eller opdatere dine undersøgelsesoplysninger, bedes du kontakte register@clinicaltrials.gov. Så snart en ændring er implementeret på clinicaltrials.gov, vil denne også blive opdateret automatisk på vores hjemmeside .
Kliniske forsøg med Siltuximab, Velcade and dexamethasone
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Judit Pich MartínezAfsluttet
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Centocor, Inc.AfsluttetMyelomatoseForenede Stater, Holland
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Janssen Research & Development, LLCAfsluttetMyelomatoseForenede Stater, Frankrig, Polen, Det Forenede Kongerige, Belgien, Spanien, Tyskland, Portugal, Bulgarien, Rumænien, Holland, Grækenland, Canada, Den Russiske Føderation, Ungarn, Brasilien, Slovakiet, Tjekkiet
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M.D. Anderson Cancer CenterJanssen Services, LLCAfsluttet
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GlaxoSmithKlineAfsluttetKvalme | Opkastning | Kvalme og opkastning, kemoterapi-induceretForenede Stater, Tyskland, Bulgarien, Ungarn, Filippinerne, Den Russiske Føderation, Taiwan, Korea, Republikken, Belgien, Danmark, Hong Kong, Slovakiet, Sydafrika, Spanien, Irland, Letland, Thailand, Italien, Det Forenede Kongerige og mere