- ICH GCP
- Amerikanska kliniska prövningsregistret
- Klinisk prövning NCT01266811
A Phase 3 Study of Siltuximab or Placebo in Combination With Velcade and Dexamethasone in Patients With Relapsed or Refractory Multiple Myeloma
25 januari 2013 uppdaterad av: 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.
Studieöversikt
Status
Indragen
Betingelser
Intervention / Behandling
Detaljerad beskrivning
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.
Studietyp
Interventionell
Fas
- Fas 3
Kontakter och platser
Det här avsnittet innehåller kontaktuppgifter för dem som genomför studien och information om var denna studie genomförs.
Studieorter
-
-
-
Adelaide, Australien
-
Camperdown, Australien
-
Heidelberg, Australien
-
Parkville, Australien
-
Prahran, Australien
-
-
-
-
-
Edegem, Belgien
-
Liège, Belgien
-
Turnhout, Belgien
-
Yvoir, Belgien
-
-
-
-
-
Plovdiv N/A, Bulgarien
-
Sofia, Bulgarien
-
Varna, Bulgarien
-
-
-
-
Iowa
-
Iowa City, Iowa, Förenta staterna
-
-
Massachusetts
-
Boston, Massachusetts, Förenta staterna
-
-
Ohio
-
Toledo, Ohio, Förenta staterna
-
-
Pennsylvania
-
Willow Grove, Pennsylvania, Förenta staterna
-
-
Wisconsin
-
Milwaukee, Wisconsin, Förenta staterna
-
-
-
-
-
Gandhinagar Guiarat, Indien
-
-
-
-
-
Ankara, Kalkon
-
Bursa, Kalkon
-
Edirne, Kalkon
-
-
-
-
-
Toronto, Kanada
-
-
-
-
-
Hwasun Gun, Korea, Republiken av
-
Seoul, Korea, Republiken av
-
-
-
-
-
Apeldoorn, Nederländerna
-
Deventer, Nederländerna
-
Zwolle, Nederländerna
-
-
-
-
-
Christchurch, Nya Zeeland
-
Grafton, Nya Zeeland
-
Nz 9 Takapuna Auckland, Nya Zeeland
-
Palmerston North, Nya Zeeland
-
-
-
-
-
Brzozow, Polen
-
Gdansk, Polen
-
Lodz, Polen
-
Opole, Polen
-
Wroclaw, Polen
-
-
-
-
-
Nottingham, Storbritannien
-
-
-
-
-
Hradec Kralove, Tjeckien
-
Liberec, Tjeckien
-
Praha, Tjeckien
-
Praha 2, Tjeckien
-
-
-
-
-
Cherkassy, Ukraina
-
Dnepropetrovsk, Ukraina
-
Kharkov, Ukraina
-
Khmelnitskiy, Ukraina
-
Kiev, Ukraina
-
Odessa, Ukraina
-
Simferopol, Ukraina
-
Vinnitsa, Ukraina
-
-
Deltagandekriterier
Forskare letar efter personer som passar en viss beskrivning, så kallade behörighetskriterier. Några exempel på dessa kriterier är en persons allmänna hälsotillstånd eller tidigare behandlingar.
Urvalskriterier
Åldrar som är berättigade till studier
18 år och äldre (Vuxen, Äldre vuxen)
Tar emot friska volontärer
Nej
Kön som är behöriga för studier
Allt
Beskrivning
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
Det här avsnittet ger detaljer om studieplanen, inklusive hur studien är utformad och vad studien mäter.
Hur är studien utformad?
Designdetaljer
- Primärt syfte: Behandling
- Tilldelning: Randomiserad
- Interventionsmodell: Parallellt uppdrag
- Maskning: Fyrdubbla
Vapen och interventioner
Deltagargrupp / Arm |
Intervention / Behandling |
---|---|
Experimentell: 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
|
Given in 21-day treatment cycles
|
Övrig: 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
|
Siltuximab 11 mg/kg as 1 hour IV infusion on Day 1 of every cycle
|
Vad mäter studien?
Primära resultatmått
Resultatmått |
Tidsram |
---|---|
Progression-free survival (PFS)
Tidsram: Event driven, i.e. every 3-4 weeks until progression, death, or end of study (5 years after first patient is dosed)
|
Event driven, i.e. every 3-4 weeks until progression, death, or end of study (5 years after first patient is dosed)
|
Sekundära resultatmått
Resultatmått |
Tidsram |
---|---|
Overall survival
Tidsram: Every 3 months until death or end of study (5 years after 1st patient is dosed)
|
Every 3 months until death or end of study (5 years after 1st patient is dosed)
|
Overall response rate
Tidsram: Every 3 weeks until disease progression or end of study (5 years after 1st patient is dosed)
|
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
Tidsram: Day 1 of Cycles 1, 2, 3, 5, 7, 11, 15, and 19 and during the follow-up period (12 weeks after last dose)
|
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
Tidsram: Pre-dose on Day 1 of Cycles 1, 2 and 3; at Cycle 3 measured 1, 2, 4, 6 and 24 hours after dose
|
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
Tidsram: Routinely until 30 days after last dose at a minimum, or until end of study
|
Routinely until 30 days after last dose at a minimum, or until end of study
|
Samarbetspartners och utredare
Det är här du hittar personer och organisationer som är involverade i denna studie.
Sponsor
Studieavstämningsdatum
Dessa datum spårar framstegen för inlämningar av studieposter och sammanfattande resultat till ClinicalTrials.gov. Studieposter och rapporterade resultat granskas av National Library of Medicine (NLM) för att säkerställa att de uppfyller specifika kvalitetskontrollstandarder innan de publiceras på den offentliga webbplatsen.
Studera stora datum
Studiestart
1 juli 2011
Primärt slutförande (Förväntat)
1 april 2014
Avslutad studie (Förväntat)
1 december 2014
Studieregistreringsdatum
Först inskickad
23 december 2010
Först inskickad som uppfyllde QC-kriterierna
23 december 2010
Första postat (Uppskatta)
24 december 2010
Uppdateringar av studier
Senaste uppdatering publicerad (Uppskatta)
28 januari 2013
Senaste inskickade uppdateringen som uppfyllde QC-kriterierna
25 januari 2013
Senast verifierad
1 januari 2013
Mer information
Termer relaterade till denna studie
Nyckelord
Ytterligare relevanta MeSH-villkor
- Hjärt-kärlsjukdomar
- Kärlsjukdomar
- Immunsystemets sjukdomar
- Neoplasmer efter histologisk typ
- Neoplasmer
- Lymfoproliferativa störningar
- Immunproliferativa störningar
- Hematologiska sjukdomar
- Hemorragiska störningar
- Hemostatiska störningar
- Paraproteinemier
- Blodproteinstörningar
- Multipelt myelom
- Neoplasmer, Plasmacell
- Läkemedels fysiologiska effekter
- Molekylära mekanismer för farmakologisk verkan
- Autonoma agenter
- Agenter från det perifera nervsystemet
- Enzyminhibitorer
- Antiinflammatoriska medel
- Antineoplastiska medel
- Antiemetika
- Gastrointestinala medel
- Glukokortikoider
- Hormoner
- Hormoner, hormonsubstitut och hormonantagonister
- Antineoplastiska medel, hormonella
- Proteashämmare
- Dexametason
- Dexametasonacetat
- BB 1101
- Bortezomib
- Siltuximab
Andra studie-ID-nummer
- CR017743
- CNTO328MMY3001 (Annan identifierare: Centocor, Inc.)
Denna information hämtades direkt från webbplatsen clinicaltrials.gov utan några ändringar. Om du har några önskemål om att ändra, ta bort eller uppdatera dina studieuppgifter, vänligen kontakta register@clinicaltrials.gov. Så snart en ändring har implementerats på clinicaltrials.gov, kommer denna att uppdateras automatiskt även på vår webbplats .
Kliniska prövningar på Multipelt myelom
-
Lawson Health Research InstituteThe Ottawa Hospital; Hamilton Health Sciences Corporation; Dalhousie University och andra samarbetspartnersAktiv, inte rekryterandeMultipelt myelom vid återfall | Multipelt myelom med misslyckad remission | Multipelt myelom stadium I | Multipelt myelomprogression | Multipelt myelom steg II | Multipelt myelom steg IIIKanada
-
Fred Hutchinson Cancer Research Center/University...National Cancer Institute (NCI)AvslutadSteg I multipelt myelom | Steg II multipelt myelom | Steg III multipelt myelom | Refraktärt multipelt myelomFörenta staterna
-
Case Comprehensive Cancer CenterNational Cancer Institute (NCI)AvslutadSteg I multipelt myelom | Steg II multipelt myelom | Steg III multipelt myelom | Refraktärt multipelt myelomFörenta staterna
-
Mayo ClinicAvslutadMultipelt myelom | Steg I multipelt myelom | Steg II multipelt myelom | Steg III multipelt myelom | Refraktärt multipelt myelomFörenta staterna
-
National Cancer Institute (NCI)AvslutadSteg I multipelt myelom | Steg II multipelt myelom | Steg III multipelt myelom | Refraktärt multipelt myelomFörenta staterna
-
National Cancer Institute (NCI)AvslutadSteg I multipelt myelom | Steg II multipelt myelom | Steg III multipelt myelom | Refraktärt multipelt myelomFörenta staterna
-
City of Hope Medical CenterAvslutadSteg I multipelt myelom | Steg II multipelt myelom | Steg III multipelt myelom | Refraktärt multipelt myelomFörenta staterna
-
University of WashingtonNational Cancer Institute (NCI)AvslutadSteg I multipelt myelom | Steg II multipelt myelom | Steg III multipelt myelom | Refraktärt multipelt myelomFörenta staterna
-
Fred Hutchinson Cancer CenterNational Cancer Institute (NCI)AvslutadSteg I multipelt myelom | Steg II multipelt myelom | Steg III multipelt myelom | Refraktärt multipelt myelomFörenta staterna
-
Barbara Ann Karmanos Cancer InstituteNational Cancer Institute (NCI)AvslutadSteg I multipelt myelom | Steg II multipelt myelom | Steg III multipelt myelom | Refraktärt multipelt myelomFörenta staterna