A Study of the Safety and Efficacy of CNTO 328 and Bortezomib to Bortezomib Alone in Patients With Relapsed or Refractory Multiple Myeloma

NCT ID: NCT00401843

Last Updated: 2019-11-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 307 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-11-28
• Study Completion Date: 2019-09-24

Brief Summary

The purpose of Part 1 of the study is to determine the safety of the combination of Siltuximab (CNTO 328) and bortezomib (Velcade). The purpose of Part 2 of the study is to compare the length of progression free survival for those patients given CNTO 328 and bortezomib to those patients given bortezomib alone.

Detailed Description

The purpose of this study is to see what effects CNTO 328 has on relapsed or refractory multiple myeloma. The study drug, CNTO 328, is a chimeric (part mouse) antibody (small protein that is important for fighting infection).CNTO 328 blocks a small protein called Interleukin 6 (IL-6). IL-6 is made naturally by your body, and at normal levels is important for inflammatory response. High levels of IL-6 can help cancer cells grow and interfere with chemotherapy drugs killing cancer cells. Cancer-related sickness such as cachexia (weight loss), bone resorption (weakening of your bones), and depression have been linked to high levels of IL-6. CNTO 328 has been shown to slow down tumor growth or shrink tumors when tested in animals. In other clinical trials, over 100 patients have received CNTO 328. There are studies ongoing in participants with kidney cancer, hematologic malignancies (blood cancers such as multiple myeloma), and prostate cancer, to see if CNTO 328 is safe and to see what effects it has on these types of cancer. At this time, it is unknown what effect CNTO 328 has had on the participants' cancer. Bortezomib is a type of drug known as a "proteasome inhibitor." A proteasome is a substance that is found in every cell and it is there to help to break down other substances ('proteins') and has a role in the way cells divide. If the proteasome is inhibited, it cannot perform its function in the cell, and if a cell cannot divide it dies. Over 8000 patients with multiple myeloma and other types of cancer have been treated with bortezomib. Bortezomib has been extensively studied in patients with previously treated multiple myeloma. Based on its established activity in pretreated multiple myeloma, bortezomib is registered in the United States and in Europe for the treatment of multiple myeloma patients who have received at least two prior therapies and have demonstrated disease progression on the last therapy. Bortezomib is currently also being studied in several other cancer types.This study consists of two parts. The purpose of Part 1 is to determine the safety of CNTO 328 and bortezomib when given together as a treatment. The purpose of Part 2 is to compare the safety and effects (good and bad) of the combination of CNTO 328 and bortezomib to the safety and effects of bortezomib alone. About 20 patients will take part in the first part of the study. About 270 patients will take part in the second part of the study at approximately 70 sites in the US, Canada, and Europe. Patients will be in the study for about 12 months, with a follow-up period of around 9 months. The study is divided into four different phases: Screening phase-which lasts up to 4 weeks. During this phase the study doctor will perform tests to see if the patient can participate in the study.Treatment phase-which may last up to 4 cycles of 42 days each during which the patient will be treated with CNTO 328 and bortezomib. Maintenance phase-If the patient benefits from the therapy in the treatment phase, the patient will continue to receive CNTO 328 and bortezomib, but now in cycles of 35 days each. Follow up phase, this includes an end of treatment visit 4 weeks after the patient's last infusion and follow up visits every three months until the patient starts a new anti-cancer treatment. CNTO 328 6mg/kg ( 6 milligrams per kilogram of body weight) will be given intravenously (into the vein) over 2 hours once every 2 weeks. Patients who respond with stable disease or better may receive additional doses. Bortezomib will be given IV (into the vein) at 1.3 mg/m2 over 3-5 seconds twice a week for 2 weeks followed by 1 week of rest.

Conditions

Multiple Myeloma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Part 1: Siltuximab Plus Bortezomib

Siltuximab 6 milligram per kilogram (mg/kg) will be administered as intravenous infusion once every 2 weeks along with bortezomib 1.3 milligram per square meter (mg/m\^2) during cycle 1.

Group Type: EXPERIMENTAL

Siltuximab

Intervention Type: BIOLOGICAL

Siltuximab 6 mg/kg will be administered as intravenous infusion once every 2 weeks during cycle 1 in Part 1. Siltuximab 6 mg/kg will be administered as intravenous infusion once every 2 weeks during 42-day Treatment Phase and 35-day Maintenance Phase in Part 2.

Bortezomib

Intervention Type: DRUG

Bortezomib 1.3 mg/m\^2 will be administered as intravenous bolus once every 2 weeks during cycle 1 in Part 1. Bortezomib 1.3 mg/m\^2 will be administered as intravenous bolus on Days 1, 4, 8, 11, followed by a 10-day rest period; and on Days 22, 25, 29, and 32 followed by a 10-day rest period during 42-day treatment phase in Part 2. Bortezomib 1.3 mg/m2 will be administered as intravenous bolus on Days 1, 8, 15, 22 followed by a 13-day rest period (cycle Days 23 to 35) during 35-day Maintenance Phase in Part 2.

Part 2: Bortezomib + Placebo

Bortezomib 1.3 mg/m\^2 will be administered as intravenous bolus on Days 1, 4, 8, 11, followed by a 10-day rest period; and on Days 22, 25, 29, and 32 followed by a 10-day rest period along with matching placebo administered as intravenous infusion once every 2 weeks during 42-day treatment phase. Bortezomib 1.3 mg/m\^2 will be administered as intravenous bolus on Days 1, 8, 15, 22 followed by a 13-day rest period (cycle Days 23 to 35) along with matching placebo once every 2 weeks during 35-day Maintenance Phase. Dexamethasone tablet will be administered at first occurrence of documented disease progression or if bortezomib was discontinued due to intolerable toxicity. Dexamethasone 40 milligram per day (mg/day) will be administered on days 1-4, 9-12, and 17-20 for four 28-day cycles then 40 mg/day for Days 1-4 for all subsequent cycles.

Group Type: EXPERIMENTAL

Bortezomib

Intervention Type: DRUG

Bortezomib 1.3 mg/m\^2 will be administered as intravenous bolus once every 2 weeks during cycle 1 in Part 1. Bortezomib 1.3 mg/m\^2 will be administered as intravenous bolus on Days 1, 4, 8, 11, followed by a 10-day rest period; and on Days 22, 25, 29, and 32 followed by a 10-day rest period during 42-day treatment phase in Part 2. Bortezomib 1.3 mg/m2 will be administered as intravenous bolus on Days 1, 8, 15, 22 followed by a 13-day rest period (cycle Days 23 to 35) during 35-day Maintenance Phase in Part 2.

Placebo

Intervention Type: DRUG

Matching placebo will be administered as intravenous infusion once every 2 weeks during 42-day treatment phase and 35-day maintenance phase in Part 2.

Dexamethasone

Intervention Type: DRUG

Dexamethasone tablet will be administered in this study at the first occurrence of documented disease progression or if bortezomib was discontinued due to intolerable toxicity. Dexamethasone 40 mg/day will be administered on days 1-4, 9-12, and 17-20 for four 28-day cycles then 40 mg/day for Days 1-4 for all subsequent cycles in treatment phase and maintenance phase of Part 2.

Part 2: Bortezomib + Siltuximab

Bortezomib 1.3 mg/m\^2 will be administered as intravenous bolus on Days 1, 4, 8, 11, followed by a 10-day rest period; and on Days 22, 25, 29, and 32 followed by a 10-day rest period along with Siltuximab administered as intravenous infusion once every 2 weeks during 42-day treatment phase. Bortezomib 1.3 mg/m\^2 will be administered as intravenous bolus on Days 1, 8, 15, 22 followed by a 13-day rest period (cycle Days 23 to 35) along with Siltuximab administered as intravenous infusion once every 2 weeks for 35-day Maintenance Phase. Dexamethasone tablet will be administered at first occurrence of documented disease progression or if bortezomib was discontinued due to intolerable toxicity. Dexamethasone 40 mg/day will be administered on days 1-4, 9-12, and 17-20 for four 28-day cycles then 40 mg/day for Days 1-4 for all subsequent cycles.

Group Type: EXPERIMENTAL

Siltuximab

Intervention Type: BIOLOGICAL

Siltuximab 6 mg/kg will be administered as intravenous infusion once every 2 weeks during cycle 1 in Part 1. Siltuximab 6 mg/kg will be administered as intravenous infusion once every 2 weeks during 42-day Treatment Phase and 35-day Maintenance Phase in Part 2.

Bortezomib

Intervention Type: DRUG

Bortezomib 1.3 mg/m\^2 will be administered as intravenous bolus once every 2 weeks during cycle 1 in Part 1. Bortezomib 1.3 mg/m\^2 will be administered as intravenous bolus on Days 1, 4, 8, 11, followed by a 10-day rest period; and on Days 22, 25, 29, and 32 followed by a 10-day rest period during 42-day treatment phase in Part 2. Bortezomib 1.3 mg/m2 will be administered as intravenous bolus on Days 1, 8, 15, 22 followed by a 13-day rest period (cycle Days 23 to 35) during 35-day Maintenance Phase in Part 2.

Dexamethasone

Intervention Type: DRUG

Dexamethasone tablet will be administered in this study at the first occurrence of documented disease progression or if bortezomib was discontinued due to intolerable toxicity. Dexamethasone 40 mg/day will be administered on days 1-4, 9-12, and 17-20 for four 28-day cycles then 40 mg/day for Days 1-4 for all subsequent cycles in treatment phase and maintenance phase of Part 2.

Interventions

Siltuximab

Siltuximab 6 mg/kg will be administered as intravenous infusion once every 2 weeks during cycle 1 in Part 1. Siltuximab 6 mg/kg will be administered as intravenous infusion once every 2 weeks during 42-day Treatment Phase and 35-day Maintenance Phase in Part 2.

Intervention Type: BIOLOGICAL

Bortezomib

Bortezomib 1.3 mg/m\^2 will be administered as intravenous bolus once every 2 weeks during cycle 1 in Part 1. Bortezomib 1.3 mg/m\^2 will be administered as intravenous bolus on Days 1, 4, 8, 11, followed by a 10-day rest period; and on Days 22, 25, 29, and 32 followed by a 10-day rest period during 42-day treatment phase in Part 2. Bortezomib 1.3 mg/m2 will be administered as intravenous bolus on Days 1, 8, 15, 22 followed by a 13-day rest period (cycle Days 23 to 35) during 35-day Maintenance Phase in Part 2.

Intervention Type: DRUG

Placebo

Matching placebo will be administered as intravenous infusion once every 2 weeks during 42-day treatment phase and 35-day maintenance phase in Part 2.

Intervention Type: DRUG

Dexamethasone

Dexamethasone tablet will be administered in this study at the first occurrence of documented disease progression or if bortezomib was discontinued due to intolerable toxicity. Dexamethasone 40 mg/day will be administered on days 1-4, 9-12, and 17-20 for four 28-day cycles then 40 mg/day for Days 1-4 for all subsequent cycles in treatment phase and maintenance phase of Part 2.

Intervention Type: DRUG

Other Intervention Names

CNTO 328; VELCADE

Eligibility Criteria

Inclusion Criteria

• Measurable secretory disease defined as either serum monoclonal paraprotein, (M-protein) greater than or equal to (>=)1 gram per deciliter (g/dL) or urine monoclonal (light chain) protein (> 200 mg/24 hours)
• Documented disease progression after at least 1 prior line of therapy but no more than 3 or have had no response to previous treatment (primary refractory disease)
• ECOG performance status score of less than or equal to (<=) 2
• Adequate bone marrow, liver, and renal function

Exclusion Criteria

• No prior treatment with bortezomib
• Not Refractory to high-dose dexamethasone
• Not >= Grade 2 peripheral neuropathy
• Have not received an allogeneic bone marrow or allogeneic peripheral blood stem cell transplant
• No prior or concomitant malignancy (other than multiple myeloma) except adequately treated basal cell or squamous cell carcinoma of the skin, carcinoma in situ of the cervix, or other cancer for which the patient has been disease-free for <= 3 years

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 99 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, LLC Clinical Trial

Role: STUDY_DIRECTOR

Janssen Research & Development, LLC

Locations

Greenbrae, California, United States

Los Angeles, California, United States

Indianapolis, Indiana, United States

Albuquerque, New Mexico, United States

New York, New York, United States

Syracuse, New York, United States

Chapel Hill, North Carolina, United States

North Charleston, South Carolina, United States

Dallas, Texas, United States

Houston, Texas, United States

Madison, Wisconsin, United States

Antwerp, , Belgium

B-8000 Brugge, , Belgium

Brussels, , Belgium

Edegem, , Belgium

Leuven, , Belgium

Rio de Janeiro, , Brazil

Bulgaria, , Bulgaria

Pleven, , Bulgaria

Plovdiv, , Bulgaria

Vancouver, British Columbia, Canada

Québec, Quebec, Canada

Calgary, , Canada

Brno, , Czechia

Hradec Králové, , Czechia

Prague, , Czechia

Grenoble, , France

Lille Cedex N/a, , France

Montpellier, , France

Pierre-Bénite, , France

Vandœuvre-lès-Nancy, , France

Aschaffenburg, , Germany

Essen, , Germany

Mainz, , Germany

Münster, , Germany

Stuttgart, , Germany

Ulm, , Germany

Athens, , Greece

Budapest, , Hungary

Debrecen, , Hungary

Gyõr, , Hungary

Nyíregyháza, , Hungary

Szeged, , Hungary

Amersfoort, , Netherlands

Amsterdam, , Netherlands

Rotterdam, , Netherlands

The Hague, , Netherlands

Bialystok, , Poland

Gdansk, , Poland

Katowice, , Poland

Lodz, , Poland

Lublin, , Poland

Poznan, , Poland

Wroclaw, , Poland

Coimbra, , Portugal

Lisbon, , Portugal

Porto, , Portugal

Baia Mare, , Romania

Brasov, , Romania

Bucharest, , Romania

Iași, , Romania

Tg Mures, , Romania

Arkhangelsk, , Russia

Izhevsk, , Russia

Moscow, , Russia

Nizhny Novgorod, , Russia

Novosibirsk, , Russia

Saint Petersburg, , Russia

Ufa, , Russia

Bratislava, , Slovakia

Martin, , Slovakia

Badalona, , Spain

Barcelona, , Spain

Madrid, , Spain

Salamanca, , Spain

Valencia, , Spain

London, , United Kingdom

Nottingham, , United Kingdom

Plymouth, , United Kingdom

Sutton, , United Kingdom

Countries

United States; Belgium; Brazil; Bulgaria; Canada; Czechia; France; Germany; Greece; Hungary; Netherlands; Poland; Portugal; Romania; Russia; Slovakia; Spain; United Kingdom

References

Orlowski RZ, Gercheva L, Williams C, Sutherland H, Robak T, Masszi T, Goranova-Marinova V, Dimopoulos MA, Cavenagh JD, Spicka I, Maiolino A, Suvorov A, Blade J, Samoylova O, Puchalski TA, Reddy M, Bandekar R, van de Velde H, Xie H, Rossi JF. A phase 2, randomized, double-blind, placebo-controlled study of siltuximab (anti-IL-6 mAb) and bortezomib versus bortezomib alone in patients with relapsed or refractory multiple myeloma. Am J Hematol. 2015 Jan;90(1):42-9. doi: 10.1002/ajh.23868.

Reference Type: DERIVED

PMID: 25294016 (View on PubMed)

Other Identifiers

C0328T06

Identifier Type: OTHER

Identifier Source: secondary_id

2006-001904-36

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CR012784

Identifier Type: -

Identifier Source: org_study_id