A Study to Compare CNTO 328 (Anti-IL-6 Monoclonal Antibody) and VELCADE-Melphalan-Prednisone (VMP) With VMP Alone in Previously Untreated Multiple Myeloma Patients

NCT00911859 | Completed Phase 2 Results DMC

• 3 other identifiers: CR015901CNTO328MMY20012008-007157-12
• Study Type: interventional
• Target: 118
• Locations: 11 countries
• Sites: 37

Brief Summary

The purpose of this study is to evaluate safety and effectiveness of CNTO 328 (siltuximab) when it is administered together with velcade-melphalan-prednisone (VMP) in comparison with VMP alone in participants with multiple myeloma (a type of cancer that affects the blood and bone marrow).

Conditions

Multiple Myeloma

Keywords

Multiple Myeloma; CNTO328; Interleukin-6 (IL-6); Monoclonal antibody; Anti-IL-6 monoclonal antibody; Bortezomib; Velcade; Melphalan; Prednisone

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants Who Achieved Complete Response (CR) - European Group for Blood and Marrow Transplantation (EBMT) Criteria

  CR was assessed using EMBT criteria: disappearance of the original monoclonal paraprotein from the blood and urine on at least 2 determinations for a minimum of 6 weeks by immunofixation studies, \<5% plasma cells in the bone marrow on at least 1 determination, if skeletal survey is available: no increase in the size or number of lytic bone lesions (development of a compression fracture does not exclude response), disappearance of soft tissue plasmacytomas for at least 6 weeks.

  Up to disease progression, approximately 3 years

Secondary Outcomes (8)

• Percentage of Participants Who Achieved Overall Response ie, Complete Response (CR) or Partial Response (PR) - European Group for Blood and Marrow Transplantation (EBMT) Criteria

  Up to disease progression, approximately 3 years

• Percentage of Participants Who Achieved Stringent Complete Response (sCR) - International Myeloma Working Group (IMWG) Criteria

  Up to disease progression, approximately 3 years

• Progression-Free Survival (PFS)

  From the date of randomization until disease progression or death, whichever occurred first, as assessed up to the last efficacy assessment for disease progression (approximately 3 years)

• 1-year Progression-Free Survival (PFS) Rate

  1 year

• Duration of Response (DOR)

  From the date participants achieved CR or PR to either date for disease progression (including relapse from CR) or the censoring date for progressive disease, as assessed Up to 30 days after last dose of study medication

Study Arms (3)

Part 1: VMP+Siltuximab 11 mg/kg

EXPERIMENTAL

Siltuximab 11 mg/kg as a 1-hour intravenous infusion every 3 weeks along with VMP (Velcade+Melphalan+Prednisone). Velcade 1.3 mg/m2 will be administered as an intravenous bolus injection according to the current approved package inserts. Melphalan 9 mg/m2 and prednisone 60 mg/m2 will be taken orally (by mouth).

Drug: Siltuximab11 mg/kg; Drug: Velcade (bortezomib); Drug: Melphalan; Drug: Prednisone

Part 2, Arm A: VMP+Siltuximab 8.3 mg/kg or 11 mg/kg

EXPERIMENTAL

Siltuximab 8.3 mg/kg or 11 mg/kg as a 1-hour intravenous infusion every 3 weeks along with VMP. Velcade 1.3 mg/m2 will be administered as an intravenous bolus injection according to the current approved package inserts. Melphalan 9 mg/m2 and prednisone 60 mg/m2 will be taken orally

Drug: Siltuximab 8.3 mg/kg or 11 mg/kg; Drug: Velcade (bortezomib); Drug: Melphalan; Drug: Prednisone

Part 2, Arm B: VMP

ACTIVE COMPARATOR

Velcade 1.3 mg/m2 will be administered as an intravenous bolus injection according to the current approved package inserts. Melphalan 9 mg/m2 and prednisone 60 mg/m2 will be taken orally

Drug: Velcade (bortezomib); Drug: Melphalan; Drug: Prednisone

Interventions

Siltuximab11 mg/kg DRUG

Participants will receive siltuximab 11 mg/kg as a 1-hour intravenous infusion every 3 weeks in Part 1.

Also known as: CNTO 328

Part 1: VMP+Siltuximab 11 mg/kg

Siltuximab 8.3 mg/kg or 11 mg/kg DRUG

Participants will receive siltuximab 8.3 mg/kg or 11 mg/kg as a 1-hour intravenous infusion every 3 weeks for 9 cycles of treatment in Part 2, Arm A and in maintenance period.

Also known as: CNTO 328

Part 2, Arm A: VMP+Siltuximab 8.3 mg/kg or 11 mg/kg

Velcade (bortezomib) DRUG

Participants will receive Velcade 1.3 mg/m2 as an intravenous bolus injection according to the current approved package insert in Part 1.

Also known as: bortezomib

Part 1: VMP+Siltuximab 11 mg/kg

Melphalan DRUG

Participants will take melphalan 9 mg/m2 will be administered orally on Days 1 to 4, followed by a 38-day rest period in Part 1.

Part 1: VMP+Siltuximab 11 mg/kg

Prednisone DRUG

Participants will take prednisone 60 mg/m2 will be administered orally on Days 1 to 4, followed by a 38-day rest period in Part 1.

Part 1: VMP+Siltuximab 11 mg/kg

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Confirmed diagnosis of previously untreated multiple myeloma and not a candidate for high dose chemotherapy with stem cell transplantation
• Eastern cooperative oncology group performance status score of less than or equal to 2
• Measurable secretory disease, defined as either serum monoclonal paraprotein greater than or equal to 1 g/dL or urine monoclonal protein greater than 200 mg/24 hours
• Adequate laboratory results that will be confirmed by a study physician
• Agrees to protocol-defined use of effective contraception

You may not qualify if:

• Diagnosed with primary amyloidosis, asymptomatic or smoldering multiple myeloma or monoclonal gammopathy of undetermined significance
• Diagnosed with Waldenstrom's disease, or other conditions in which IgM M-protein is present in the absence of a clonal plasma cell infiltration with lytic bone lesions
• Received prior or current systemic therapy or stem cell transplantation for multiple myeloma
• Peripheral neuropathy or neuropathic pain (Grade 2 or higher)
• Received radiation therapy, plasmapheresis or surgery within 14 days
• Transplanted solid organ, with the exception of a corneal transplant
• Serious concurrent illness or history of uncontrolled heart disease

Sponsors & Collaborators

• Janssen Research & Development, LLC: lead

Study Sites (37)

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Boston, Massachusetts, United States

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Chapel Hill, North Carolina, United States

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Philadelphia, Pennsylvania, United States

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Houston, Texas, United States

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Adelaide, Australia

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Melbourne, Australia

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Bordeaux, France

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Montpellier, France

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Strasbourg, France

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Ahmedabad, India

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Calicut, India

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Hyderabad, India

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Jaipur, India

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Mumbai, India

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Afula, Israel

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Haifa, Israel

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Jerusalem, Israel

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Petah Tikva, Israel

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Ramat Gan, Israel

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Bialystok, Poland

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Chorzów, Poland

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Gdynia, Poland

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Lodz, Poland

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Wroclaw, Poland

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Baia Mare, Romania

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Brasov, Romania

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Iași, Romania

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Arkhangelsk, Russia

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Moscow, Russia

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Nizhny Novgorod, Russia

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Saint Petersburg, Russia

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Singapore, Singapore

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Seoul, South Korea

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Barcelona, Spain

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Madrid, Spain

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Murcia, Spain

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Salamanca, Spain

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Related Publications (1)

• San-Miguel J, Blade J, Shpilberg O, Grosicki S, Maloisel F, Min CK, Polo Zarzuela M, Robak T, Prasad SV, Tee Goh Y, Laubach J, Spencer A, Mateos MV, Palumbo A, Puchalski T, Reddy M, Uhlar C, Qin X, van de Velde H, Xie H, Orlowski RZ. Phase 2 randomized study of bortezomib-melphalan-prednisone with or without siltuximab (anti-IL-6) in multiple myeloma. Blood. 2014 Jun 26;123(26):4136-42. doi: 10.1182/blood-2013-12-546374. Epub 2014 May 15.

  PMID: 24833354 DERIVED

MeSH Terms

Conditions

Multiple Myeloma

Interventions

siltuximab; Bortezomib; Melphalan; Prednisone

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Results Point of Contact

• Title: Senior Director
• Organization: Janssen R&D BE

ClinicalTrialDisclosure@its.jnj.com

Study Officials

• Janssen Research & Development L.L.C Clinical Trial

  Janssen Research & Development L.L.C

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 29, 2009
• First Posted: June 2, 2009
• Study Start: June 1, 2009
• Primary Completion: April 1, 2013
• Study Completion: April 1, 2013
• Last Updated: November 18, 2014
• Results First Posted: November 18, 2014

Record last verified: 2014-11

Locations

KR (1); US (4); IL (5); FR (3); AU (2); IN (5); RO (3); PL (5); RU (4); SG (1); ES (4)