Clinical trial NCT00911859: 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
Official 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Multiple Myeloma
Keywords: Multiple Myeloma
CNTO328
Interleukin-6 (IL-6)
Monoclonal antibody
Anti-IL-6 monoclonal antibody
Bortezomib
Velcade
Melphalan
Prednisone
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2009-06-02
Enrollment: 118
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Percentage of Participants Who Achieved Complete Response (CR) - European Group for Blood and Marrow Transplantation (EBMT) Criteria
timeFrame: Up to disease progression, approximately 3 years
Secondary outcomes:
measure: Percentage of Participants Who Achieved Overall Response ie, Complete Response (CR) or Partial Response (PR) - European Group for Blood and Marrow Transplantation (EBMT) Criteria
timeFrame: Up to disease progression, approximately 3 years
measure: Percentage of Participants Who Achieved Stringent Complete Response (sCR) - International Myeloma Working Group (IMWG) Criteria
timeFrame: Up to disease progression, approximately 3 years
measure: Progression-Free Survival (PFS)
timeFrame: 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)
measure: 1-year Progression-Free Survival (PFS) Rate
timeFrame: 1 year
measure: Duration of Response (DOR)
timeFrame: 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
measure: 1-year Survival Rate
timeFrame: 1 year
measure: Overall Survival
timeFrame: From the date of randomization till the date of death, as assessed up to the end of study (approximately 3 years)
measure: 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)
timeFrame: Baseline (Day 1 predose) and Cycle 9 (Week 54)
Other outcomes:
Locations:
city: Boston
country: United States
state: Massachusetts
city: Chapel Hill
country: United States
state: North Carolina
city: Philadelphia
country: United States
state: Pennsylvania
city: Houston
country: United States
state: Texas
city: Adelaide
country: Australia
city: Melbourne
country: Australia
city: Bordeaux Cedex
country: France
city: Montpellier
country: France
city: Strasbourg
country: France
city: Ahmedabad
country: India
city: Calicut
country: India
city: Hyderabad N/A
country: India
city: Jaipur
country: India
city: Mumbai
country: India
city: Afula
country: Israel
city: Haifa
country: Israel
city: Jerusalem
country: Israel
city: Petah Tikva
country: Israel
city: Ramat-Gan
country: Israel
city: Seoul
country: Korea, Republic of
city: Bialystok
country: Poland
city: Chorzów
country: Poland
city: Gdynia
country: Poland
city: Lodz
country: Poland
city: Wroclaw
country: Poland
city: Baia Mare
country: Romania
city: Brasov
country: Romania
city: Iasi
country: Romania
city: Arkhangelsk
country: Russian Federation
city: Moscow N/A
country: Russian Federation
city: Nizhni Novgorod
country: Russian Federation
city: St. Petersburg
country: Russian Federation
city: Singapore
country: Singapore
city: Barcelona
country: Spain
city: Madrid
country: Spain
city: Murcia N/A
country: Spain
city: Salamanca
country: Spain
Study officials:
affiliation: Janssen Research & Development L.L.C
name: Janssen Research & Development L.L.C Clinical Trial
role: STUDY_DIRECTOR
References:
citation: 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.