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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT00911859




Registration number
NCT00911859
Ethics application status
Date submitted
29/05/2009
Date registered
29/05/2009
Date last updated
17/11/2014

Titles & IDs
Public title
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
Scientific title
A Randomized, Open-Label, Phase 2 Study of CNTO 328 (Anti-IL-6 Monoclonal Antibody) and VELCADE-Melphalan-Prednisone Compared With VELCADE-Melphalan-Prednisone for the Treatment of Previously Untreated Multiple Myeloma
Secondary ID [1] 0 0
CNTO328MMY2001
Secondary ID [2] 0 0
CR015901
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Multiple Myeloma 0 0
Multiple Myeloma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Other cancer types

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Siltuximab11 mg/kg
Treatment: Drugs - Siltuximab 8.3 mg/kg or 11 mg/kg
Treatment: Drugs - Velcade (bortezomib)
Treatment: Drugs - Velcade (bortezomib)
Treatment: Drugs - Melphalan
Treatment: Drugs - Melphalan
Treatment: Drugs - Prednisone
Treatment: Drugs - Prednisone
Treatment: Drugs - Velcade (bortezomib)
Treatment: Drugs - Melphalan
Treatment: Drugs - Prednisone
Treatment: Drugs - Siltuximab11 mg/kg
Treatment: Drugs - Siltuximab 8.3 mg/kg or 11 mg/kg
Treatment: Drugs - Velcade (bortezomib)
Treatment: Drugs - Velcade (bortezomib)
Treatment: Drugs - Melphalan
Treatment: Drugs - Melphalan
Treatment: Drugs - Prednisone
Treatment: Drugs - Prednisone
Treatment: Drugs - Velcade (bortezomib)
Treatment: Drugs - Melphalan
Treatment: Drugs - Prednisone

Experimental: 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).

Experimental: 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

Active Comparator: 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

Experimental: 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).

Experimental: 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

Active Comparator: 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


Treatment: Drugs: Siltuximab11 mg/kg
Participants will receive siltuximab 11 mg/kg as a 1-hour intravenous infusion every 3 weeks in Part 1.

Treatment: Drugs: 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.

Treatment: Drugs: 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.

Treatment: Drugs: 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)

Treatment: Drugs: 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.

Treatment: Drugs: 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.

Treatment: Drugs: 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.

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

Treatment: Drugs: Velcade (bortezomib)
Participants will receive Velcade 1.3 mg/m2 as an intravenous bolus injection according to the current approved package insert.

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

Treatment: Drugs: Prednisone
Participants will take prednisone 60 mg/m2 orally according to the package insert.

Treatment: Drugs: Siltuximab11 mg/kg
Participants will receive siltuximab 11 mg/kg as a 1-hour intravenous infusion every 3 weeks in Part 1.

Treatment: Drugs: 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.

Treatment: Drugs: 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.

Treatment: Drugs: 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)

Treatment: Drugs: 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.

Treatment: Drugs: 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.

Treatment: Drugs: 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.

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

Treatment: Drugs: Velcade (bortezomib)
Participants will receive Velcade 1.3 mg/m2 as an intravenous bolus injection according to the current approved package insert.

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

Treatment: Drugs: Prednisone
Participants will take prednisone 60 mg/m2 orally according to the package insert.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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.
Timepoint [1] 0 0
Up to disease progression, approximately 3 years
Primary outcome [2] 0 0
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.
Timepoint [2] 0 0
Up to disease progression, approximately 3 years
Secondary outcome [1] 0 0
Percentage of Participants Who Achieved Overall Response ie, Complete Response (CR) or Partial Response (PR) - European Group for Blood and Marrow Transplantation (EBMT) Criteria - CR or PR was assessed using EBMT criteria. CR: 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; PR: >=50% reduction in the level of serum monoclonal paraprotein for at least 2 determinations 6 weeks apart, if present, reduction in 24-hour urinary light chain excretion by either >=90% or to <200 mg for at least 2 determinations 6 weeks apart, >=50% reduction in the size of soft tissue plasmacytomas (by clinical or radiographic examination) for at least 6 weeks, if skeletal survey is available: no increase in size or number of lytic bone lesions
Timepoint [1] 0 0
Up to disease progression, approximately 3 years
Secondary outcome [2] 0 0
Percentage of Participants Who Achieved Stringent Complete Response (sCR) - International Myeloma Working Group (IMWG) Criteria - sCR was assesses by IMWG Criteria: Negative immunofixation on the serum and urine, disappearance of any soft tissue plasmacytomas, <=5% plasma cells in bone marrow, normal free light chain ratio, absence of clonal cells in bone marrow by immunohistochemistry or immunofluorescence. sCR is a CR that has been confirmed by immunofixation + free light chain assay + either bone marrow immunohistochemistry or immunofluorescence
Timepoint [2] 0 0
Up to disease progression, approximately 3 years
Secondary outcome [3] 0 0
Progression-Free Survival (PFS) - PFS was defined as the time between randomization and either disease progression or death, whichever occurred first.
Timepoint [3] 0 0
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)
Secondary outcome [4] 0 0
1-year Progression-Free Survival (PFS) Rate - The 1-year PFS rate was defined as the percentage of participants surviving 1 year after randomization without disease progression or death.
Timepoint [4] 0 0
1 year
Secondary outcome [5] 0 0
Duration of Response (DOR) - DOR was defined as length from the earliest date a participant achieved a complete response (CR) or partial response (PR) to either date for disease progression (including relapse from CR) or the censoring date for progressive disease. Responders without disease progression were censored at the last efficacy assessment for disease progression.
Timepoint [5] 0 0
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
Secondary outcome [6] 0 0
1-year Survival Rate - Percentage of participants who are alive at the end of year 1 after randomization
Timepoint [6] 0 0
1 year
Secondary outcome [7] 0 0
Overall Survival - Overall survival is defined as the time interval in days between the date of randomization and the participant's death from any cause.
Timepoint [7] 0 0
From the date of randomization till the date of death, as assessed up to the end of study (approximately 3 years)
Secondary outcome [8] 0 0
Change From Baseline to Cycle 9 in Global Health Status/Quality of Life Subscale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ C30) - Global health status/quality of life is a subscale of the EORTC QOL C30, which comprises two questions related to overall health/quality of life during the past week. The raw score to each question ranged from 1 (very poor) to 7 (excellent). The raw mean score of health status/quality of life subscale is calculated for each participant and a linear transformation applied to standardize the raw score, so that scores range from 0 to 100; a higher score represents a higher ("better") health and quality of life.
Timepoint [8] 0 0
Baseline (Day 1 predose) and Cycle 9 (Week 54)
Secondary outcome [9] 0 0
Percentage of Participants Who Achieved Overall Response ie, Complete Response (CR) or Partial Response (PR) - European Group for Blood and Marrow Transplantation (EBMT) Criteria - CR or PR was assessed using EBMT criteria. CR: 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; PR: >=50% reduction in the level of serum monoclonal paraprotein for at least 2 determinations 6 weeks apart, if present, reduction in 24-hour urinary light chain excretion by either >=90% or to <200 mg for at least 2 determinations 6 weeks apart, >=50% reduction in the size of soft tissue plasmacytomas (by clinical or radiographic examination) for at least 6 weeks, if skeletal survey is available: no increase in size or number of lytic bone lesions
Timepoint [9] 0 0
Up to disease progression, approximately 3 years
Secondary outcome [10] 0 0
Percentage of Participants Who Achieved Stringent Complete Response (sCR) - International Myeloma Working Group (IMWG) Criteria - sCR was assesses by IMWG Criteria: Negative immunofixation on the serum and urine, disappearance of any soft tissue plasmacytomas, <=5% plasma cells in bone marrow, normal free light chain ratio, absence of clonal cells in bone marrow by immunohistochemistry or immunofluorescence. sCR is a CR that has been confirmed by immunofixation + free light chain assay + either bone marrow immunohistochemistry or immunofluorescence
Timepoint [10] 0 0
Up to disease progression, approximately 3 years
Secondary outcome [11] 0 0
Progression-Free Survival (PFS) - PFS was defined as the time between randomization and either disease progression or death, whichever occurred first.
Timepoint [11] 0 0
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)
Secondary outcome [12] 0 0
1-year Progression-Free Survival (PFS) Rate - The 1-year PFS rate was defined as the percentage of participants surviving 1 year after randomization without disease progression or death.
Timepoint [12] 0 0
1 year
Secondary outcome [13] 0 0
Duration of Response (DOR) - DOR was defined as length from the earliest date a participant achieved a complete response (CR) or partial response (PR) to either date for disease progression (including relapse from CR) or the censoring date for progressive disease. Responders without disease progression were censored at the last efficacy assessment for disease progression.
Timepoint [13] 0 0
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
Secondary outcome [14] 0 0
1-year Survival Rate - Percentage of participants who are alive at the end of year 1 after randomization
Timepoint [14] 0 0
1 year
Secondary outcome [15] 0 0
Overall Survival - Overall survival is defined as the time interval in days between the date of randomization and the participant's death from any cause.
Timepoint [15] 0 0
From the date of randomization till the date of death, as assessed up to the end of study (approximately 3 years)
Secondary outcome [16] 0 0
Change From Baseline to Cycle 9 in Global Health Status/Quality of Life Subscale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ C30) - Global health status/quality of life is a subscale of the EORTC QOL C30, which comprises two questions related to overall health/quality of life during the past week. The raw score to each question ranged from 1 (very poor) to 7 (excellent). The raw mean score of health status/quality of life subscale is calculated for each participant and a linear transformation applied to standardize the raw score, so that scores range from 0 to 100; a higher score represents a higher ("better") health and quality of life.
Timepoint [16] 0 0
Baseline (Day 1 predose) and Cycle 9 (Week 54)

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
- Adelaide
Recruitment hospital [2] 0 0
- Melbourne
Recruitment postcode(s) [1] 0 0
- Adelaide
Recruitment postcode(s) [2] 0 0
- Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Massachusetts
Country [2] 0 0
United States of America
State/province [2] 0 0
North Carolina
Country [3] 0 0
United States of America
State/province [3] 0 0
Pennsylvania
Country [4] 0 0
United States of America
State/province [4] 0 0
Texas
Country [5] 0 0
France
State/province [5] 0 0
Bordeaux Cedex
Country [6] 0 0
France
State/province [6] 0 0
Montpellier
Country [7] 0 0
France
State/province [7] 0 0
Strasbourg
Country [8] 0 0
India
State/province [8] 0 0
Ahmedabad
Country [9] 0 0
India
State/province [9] 0 0
Calicut
Country [10] 0 0
India
State/province [10] 0 0
Hyderabad N/A
Country [11] 0 0
India
State/province [11] 0 0
Jaipur
Country [12] 0 0
India
State/province [12] 0 0
Mumbai
Country [13] 0 0
Israel
State/province [13] 0 0
Afula
Country [14] 0 0
Israel
State/province [14] 0 0
Haifa
Country [15] 0 0
Israel
State/province [15] 0 0
Jerusalem
Country [16] 0 0
Israel
State/province [16] 0 0
Petah Tikva
Country [17] 0 0
Israel
State/province [17] 0 0
Ramat-Gan
Country [18] 0 0
Korea, Republic of
State/province [18] 0 0
Seoul
Country [19] 0 0
Poland
State/province [19] 0 0
Bialystok
Country [20] 0 0
Poland
State/province [20] 0 0
Chorzów
Country [21] 0 0
Poland
State/province [21] 0 0
Gdynia
Country [22] 0 0
Poland
State/province [22] 0 0
Lodz
Country [23] 0 0
Poland
State/province [23] 0 0
Wroclaw
Country [24] 0 0
Romania
State/province [24] 0 0
Baia Mare
Country [25] 0 0
Romania
State/province [25] 0 0
Brasov
Country [26] 0 0
Romania
State/province [26] 0 0
Iasi
Country [27] 0 0
Russian Federation
State/province [27] 0 0
Arkhangelsk
Country [28] 0 0
Russian Federation
State/province [28] 0 0
Moscow N/A
Country [29] 0 0
Russian Federation
State/province [29] 0 0
Nizhni Novgorod
Country [30] 0 0
Russian Federation
State/province [30] 0 0
St. Petersburg
Country [31] 0 0
Singapore
State/province [31] 0 0
Singapore
Country [32] 0 0
Spain
State/province [32] 0 0
Barcelona
Country [33] 0 0
Spain
State/province [33] 0 0
Madrid
Country [34] 0 0
Spain
State/province [34] 0 0
Murcia N/A
Country [35] 0 0
Spain
State/province [35] 0 0
Salamanca

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Janssen Research & Development, LLC
Address
Country

Ethics approval
Ethics application status

Summary
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).
Trial website
https://clinicaltrials.gov/show/NCT00911859
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Janssen Research & Development L.L.C Clinical Trial
Address 0 0
Janssen Research & Development L.L.C
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications