Clinical trial NCT00401843: A Study of the Safety and Efficacy of CNTO 328 and Bortezomib to Bortezomib Alone in Patients With Relapsed or Refractory Multiple Myeloma
Official title: A Phase 2, Randomized, Double-blind, Placebo-controlled Study Comparing the Combination of CNTO 328 (Anti-IL-6 Monoclonal Antibody) and Velcade Versus Velcade Alone in Subjects With Relapsed or Refractory Multiple Myeloma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Multiple Myeloma
Keywords: multiple myeloma
Monoclonal Antibody
Intravenous
refractory or relapsed multiple myeloma
velcade
bortezomib
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2006-11-22
Enrollment: 307
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Progression-free Survival
timeFrame: Randomization until disease progression or death, which ever occured first (maximum up to 5 years)
measure: Number of Participants With Adverse Events (AEs) or Serious Adverse Events (SAEs)
timeFrame: up to 5 years
Secondary outcomes:
measure: Percentage of Participants With Best Confirmed Response of Complete Response (CR) or Partial Response (PR) (Overall Response Rate)
timeFrame: Randomization until disease progression (maximum up to 5 years)
measure: Percentage of Participants With Confirmed Complete Response (CR Rate)
timeFrame: Randomization until disease progression (maximum up to 5 years)
measure: Overall Survival
timeFrame: up to 5 years
Other outcomes:
Locations:
city: Greenbrae
country: United States
state: California
city: Los Angeles
country: United States
state: California
city: Indianapolis
country: United States
state: Indiana
city: Albuquerque
country: United States
state: New Mexico
city: New York
country: United States
state: New York
city: Syracuse
country: United States
state: New York
city: Chapel Hill
country: United States
state: North Carolina
city: North Charleston
country: United States
state: South Carolina
city: Dallas
country: United States
state: Texas
city: Houston
country: United States
state: Texas
city: Madison
country: United States
state: Wisconsin
city: Antwerpen
country: Belgium
city: B-8000 Brugge
country: Belgium
city: Brussels
country: Belgium
city: Brussel
country: Belgium
city: Edegem
country: Belgium
city: Leuven
country: Belgium
city: Rio de Janeiro
country: Brazil
city: Bulgaria
country: Bulgaria
city: Pleven
country: Bulgaria
city: Plovdiv
country: Bulgaria
city: Vancouver
country: Canada
state: British Columbia
city: Quebec City
country: Canada
state: Quebec
city: Calgary
country: Canada
city: Brno
country: Czechia
city: Hradec Kralove
country: Czechia
city: Praha 2
country: Czechia
city: Grenoble
country: France
city: Lille Cedex N/a
country: France
city: Montpellier
country: France
city: Pierre Benite
country: France
city: Vandoeuvre Les Nancy
country: France
city: Aschaffenburg
country: Germany
city: Essen
country: Germany
city: Mainz
country: Germany
city: Münster
country: Germany
city: Stuttgart
country: Germany
city: Ulm
country: Germany
city: Athens
country: Greece
city: Budapest
country: Hungary
city: Debrecen
country: Hungary
city: Gyõr
country: Hungary
city: Nyiregyhaza N/a
country: Hungary
city: Szeged N/a
country: Hungary
city: Amersfoort
country: Netherlands
city: Amsterdam
country: Netherlands
city: Den Haag
country: Netherlands
city: Rotterdam
country: Netherlands
city: Bialystok
country: Poland
city: Gdansk
country: Poland
city: Katowice
country: Poland
city: Lodz
country: Poland
city: Lublin
country: Poland
city: Poznan
country: Poland
city: Wroclaw
country: Poland
city: Coimbra
country: Portugal
city: Lisboa N/a
country: Portugal
city: Lisboa
country: Portugal
city: Porto N/a
country: Portugal
city: Baia-Mare
country: Romania
city: Brasov
country: Romania
city: Bucharest
country: Romania
city: Bucuresti
country: Romania
city: Iasi
country: Romania
city: Tg Mures
country: Romania
city: Arkhangelsk
country: Russian Federation
city: Izhevsk
country: Russian Federation
city: Moscow N/a
country: Russian Federation
city: Moscow
country: Russian Federation
city: Nizhny Novgorod
country: Russian Federation
city: Novosibirsk
country: Russian Federation
city: St. Petersburg
country: Russian Federation
city: Ufa
country: Russian Federation
city: Bratislava
country: Slovakia
city: Martin
country: Slovakia
city: Badalona
country: Spain
city: Barcelona
country: Spain
city: Madrid
country: Spain
city: Salamanca
country: Spain
city: Valencia
country: Spain
city: London
country: United Kingdom
city: Nottingham
country: United Kingdom
city: Plymouth
country: United Kingdom
city: Sutton
country: United Kingdom
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References:
citation: 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.