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

NCT ID: NCT00911859

Last Updated: 2014-11-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 118 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-06-30
• Study Completion Date: 2013-04-30

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).

Detailed Description

The study will be conducted in 2 parts (Part 1 and Part 2) and will consist of screening period up to 2 weeks; treatment period; maintenance period (CNTO 328 hereafter referred to as siltuximab) for a maximum of 18 months and follow up period until the study ends. Part 1 is an open-label (all people know the identity of the intervention), single group safety lead-in part to evaluate the safety of siltuximab. Approximately 12 patients will be treated with siltuximab in combination with VMP. If the safety profile of the combination is acceptable, the study will proceed to Part 2. Part 2 is a randomized (the study medication is assigned by chance), open-label, 2-arm (Arm A: siltuximab + VMP; Arm B: VMP alone) study. Approximately 104 patients will be equally randomized, followed by a maintenance period with siltuximab in particiants in Arm A who achieve a partial response (PR) or better. Particiants in both parts of the study will be treated up to a maximum of nine 6-week cycles provided there is no evidence of disease progression, unacceptable toxicity, or withdrawal from treatment. Study medication will be continued for at least 2 additional cycles after confirmation of complete response, and preferably for the full 9 cycles of the treatment period. Participants who will be receiving maintenance treatment after the 12-month effectiveness analysis may continue to receive treatment with siltuximab only after careful consideration by the treating physician and on evidence of clinical benefit and in the absence of unwarranted toxicities. Safety assessments will include evaluation of adverse events, clinical laboratory tests, eastern cooperative oncology group performance status, electrocardiogram, vital signs, and physical examination which will be monitored throughout the study.

Conditions

Multiple Myeloma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Part 1: VMP+Siltuximab 11 mg/kg

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).

Group Type: EXPERIMENTAL

Siltuximab11 mg/kg

Intervention Type: DRUG

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

Velcade (bortezomib)

Intervention Type: DRUG

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

Melphalan

Intervention Type: 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.

Prednisone

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

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

Group Type: EXPERIMENTAL

Siltuximab 8.3 mg/kg or 11 mg/kg

Intervention Type: 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.

Velcade (bortezomib)

Intervention Type: DRUG

Participants will receive Velcade 1.3 mg/m2 as an intravenous bolus injection for 9 cycles of the treatment period in Part 2. It will be administered twice weekly for first 4 cycles (on Days 1, 4, 8, 11, 22, 25, 29, and 32, followed by a 10-day rest period) and once weekly for next 5 cycles (on Days 1, 8, 22, and 29, followed by a 13-day rest period)

Melphalan

Intervention Type: DRUG

Participants will receive melphalan according to currently approved package inserts. Melphalan 9 mg/m2 will be administered orally for 9 cycles of treatment period in Part 2, Arm A.

Prednisone

Intervention Type: DRUG

Participants will take prednisone 60 mg/m2 orally for 9 cycles of treatment period in Part 2, Arm A.

Part 2, Arm B: 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

Group Type: ACTIVE_COMPARATOR

Velcade (bortezomib)

Intervention Type: DRUG

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

Melphalan

Intervention Type: DRUG

Participants will take melphalan 9 mg/m2 orally according to currently approved package insert.

Prednisone

Intervention Type: DRUG

Participants will take prednisone 60 mg/m2 orally according to the package insert.

Interventions

Siltuximab11 mg/kg

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

Intervention Type: DRUG

Siltuximab 8.3 mg/kg or 11 mg/kg

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.

Intervention Type: DRUG

Velcade (bortezomib)

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

Intervention Type: DRUG

Velcade (bortezomib)

Participants will receive Velcade 1.3 mg/m2 as an intravenous bolus injection for 9 cycles of the treatment period in Part 2. It will be administered twice weekly for first 4 cycles (on Days 1, 4, 8, 11, 22, 25, 29, and 32, followed by a 10-day rest period) and once weekly for next 5 cycles (on Days 1, 8, 22, and 29, followed by a 13-day rest period)

Intervention Type: DRUG

Melphalan

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.

Intervention Type: DRUG

Melphalan

Participants will receive melphalan according to currently approved package inserts. Melphalan 9 mg/m2 will be administered orally for 9 cycles of treatment period in Part 2, Arm A.

Intervention Type: DRUG

Prednisone

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.

Intervention Type: DRUG

Prednisone

Participants will take prednisone 60 mg/m2 orally for 9 cycles of treatment period in Part 2, Arm A.

Intervention Type: DRUG

Velcade (bortezomib)

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

Intervention Type: DRUG

Melphalan

Participants will take melphalan 9 mg/m2 orally according to currently approved package insert.

Intervention Type: DRUG

Prednisone

Participants will take prednisone 60 mg/m2 orally according to the package insert.

Intervention Type: DRUG

Other Intervention Names

CNTO 328; CNTO 328; bortezomib; bortezomib; bortezomib

Eligibility Criteria

Inclusion Criteria

• 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

Exclusion Criteria

• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Janssen Research & Development, LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Janssen Research & Development L.L.C Clinical Trial

Role: STUDY_DIRECTOR

Janssen Research & Development L.L.C

Locations

Boston, Massachusetts, United States

Chapel Hill, North Carolina, United States

Philadelphia, Pennsylvania, United States

Houston, Texas, United States

Adelaide, , Australia

Melbourne, , Australia

Bordeaux, , France

Montpellier, , France

Strasbourg, , France

Ahmedabad, , India

Calicut, , India

Hyderabad, , India

Jaipur, , India

Mumbai, , India

Afula, , Israel

Haifa, , Israel

Jerusalem, , Israel

Petah Tikva, , Israel

Ramat Gan, , Israel

Bialystok, , Poland

Chorzów, , Poland

Gdynia, , Poland

Lodz, , Poland

Wroclaw, , Poland

Baia Mare, , Romania

Brasov, , Romania

Iași, , Romania

Arkhangelsk, , Russia

Moscow, , Russia

Nizhny Novgorod, , Russia

Saint Petersburg, , Russia

Singapore, , Singapore

Seoul, , South Korea

Barcelona, , Spain

Madrid, , Spain

Murcia, , Spain

Salamanca, , Spain

Countries

United States; Australia; France; India; Israel; Poland; Romania; Russia; Singapore; South Korea; Spain

References

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.

Reference Type: DERIVED

PMID: 24833354 (View on PubMed)

Other Identifiers

CNTO328MMY2001

Identifier Type: OTHER

Identifier Source: secondary_id

2008-007157-12

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CR015901

Identifier Type: -

Identifier Source: org_study_id

NCT01710241

Identifier Type: -

Identifier Source: nct_alias