NCT00401843

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

Completed Phase 2 Results posted Last updated 19 November 2019

What this trial tests

Phase 2 trial testing Siltuximab in Multiple Myeloma in 307 participants. Completed in 24 September 2019.

Timeline

28 November 2006

Primary endpoint
16 August 2011

24 September 2019

Quick facts

Lead sponsor	Janssen Research & Development, LLC
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	double
Primary purpose	treatment
Enrollment	307
Start date	28 November 2006
Primary completion	16 August 2011
Estimated completion	24 September 2019
Sites	80 locations across France, Netherlands, Russia, Greece, Slovakia, Belgium, United Kingdom, Germany

Drugs / interventions tested

• Siltuximab — full drug profile →
• Bortezomib (bortezomib) — full drug profile →
• Placebo
• Dexamethasone (dexamethasone) — full drug profile →

Conditions studied

• Multiple Myeloma — all drugs for Multiple Myeloma →

Sponsor

Janssen Research & Development, LLC — full company profile →

Who can join

Adults 18 to 99, any sex, with Multiple Myeloma. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Progression-free Survival Primary · Randomization until disease progression or death, which ever occured first (maximum up to 5 years)

Progression-free survival was defined as the time interval between randomization and the first documented sign of disease progression (including relapse from complete response \[CR\]) by the European Bone Marrow Transplant (EBMT) criteria or death, whichever occurred first. Relapse from CR requires at least 1 of the following: Reappearance of serum or urinary M-protein on immunofixation or routine electrophoresis, confirmed by at least 1 further investigation and excluding oligoclonal immune reconstitution; Greater than or equal to (\>=) 5 percent (%) plasma cells either in a bone marrow aspir

Group	Value	95% CI
Part 2 - Bortezomib + Placebo	232	191 – 302
Part 2 - Bortezomib + Siltuximab	245	217 – 300

Percentage of Participants With Best Confirmed Response of Complete Response (CR) or Partial Response (PR) (Overall Response Rate) Secondary · Randomization until disease progression (maximum up to 5 years)

Overall response rate was defined as best response (CR/PR confirmed) for a participant recorded from first administration of study agent or randomization (Part 2) until disease progression/recurrence and before dexamethasone was added. CR: Absence of original M-protein in serum/urine by immunofixation,maintained for minimum of 6 weeks. The presence of oligoclonal bands consistent with oligoclonal immune reconstitution does not exclude CR; Less than 5 percent (%) plasma cells in bone marrow aspirate and also on trephine bone biopsy if biopsy is performed; No increase in size/number of lytic bon

Group	Value	95% CI
Part 2 - Bortezomib + Placebo	46.7
Part 2 - Bortezomib + Siltuximab	55.0

Percentage of Participants With Confirmed Complete Response (CR Rate) Secondary · Randomization until disease progression (maximum up to 5 years)

CR rate was defined as the percentage of participants who achieved a confirmed CR before dexamethasone was added. CR: Absence of original M-protein in serum/urine by immunofixation,maintained for minimum of 6 weeks. The presence of oligoclonal bands consistent with oligoclonal immune reconstitution does not exclude CR; Less than 5 percent (%) plasma cells in bone marrow aspirate and also on trephine bone biopsy if biopsy is performed; No increase in size/number of lytic bone lesions; Disappearance of soft tissue plasmacytomas.

Group	Value	95% CI
Part 2 - Bortezomib + Placebo	7.3
Part 2 - Bortezomib + Siltuximab	10.7

Overall Survival Secondary · up to 5 years

Overall survival was defined as the interval between the first administration of study agent or randomization (Part 2) and the participant's death from any cause. For participants with unknown survival status as of the data cut-off date, overall survival was censored at the last date known to be alive.

Group	Value	95% CI
Part 2 - Bortezomib + Placebo	1121	1038.0 – NA
Part 2 - Bortezomib + Siltuximab	937	713 – 1127

Number of Participants With Adverse Events (AEs) or Serious Adverse Events (SAEs) Primary · up to 5 years

An AE is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; lifethreatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.

Adverse Events (AEs)

Group	Value	95% CI
Part 1 - Bortezomib + Siltuximab	21
Part 2 - Bortezomib + Placebo	138
Part 2 - Bortezomib + Siltuximab	140

Serious Adverse Events (SAEs)

Group	Value	95% CI
Part 1 - Bortezomib + Siltuximab	10
Part 2 - Bortezomib + Placebo	44
Part 2 - Bortezomib + Siltuximab	47

Adverse events — posted to ClinicalTrials.gov

Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Part 1 - Bortezomib + Siltuximab

Serious: 10/21 (48%)

Deaths: —

Part 2 - Bortezomib + Placebo

Serious: 44/139 (32%)

Deaths: —

Part 2 - Bortezomib + Siltuximab

Serious: 47/142 (33%)

Deaths: —

Serious adverse events (122 terms)

Reaction	System	Part 1 - Bortezomib + Silt…	Part 2 - Bortezomib + Plac…	Part 2 - Bortezomib + Silt…
Pneumonia	Infections and infestations	—	—	—
Sepsis	Infections and infestations	—	—	—
Anaemia	Blood and lymphatic system disorders	—	—	—
Bronchopneumonia	Infections and infestations	—	—	—
Renal Failure Acute	Renal and urinary disorders	—	—	—
Pulmonary Oedema	Respiratory, thoracic and mediastinal disorders	—	—	—
Febrile Neutropenia	Blood and lymphatic system disorders	—	—	—
Thrombocytopenia	Blood and lymphatic system disorders	—	—	—
Gastrointestinal Haemorrhage	Gastrointestinal disorders	—	—	—
Sudden Death	General disorders	—	—	—
Acute Hepatitis B	Infections and infestations	—	—	—
Erysipelas	Infections and infestations	—	—	—
Lobar Pneumonia	Infections and infestations	—	—	—
Upper Respiratory Tract Infection	Infections and infestations	—	—	—
Basal Cell Carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—	—
Syncope	Nervous system disorders	—	—	—
Renal Failure	Renal and urinary disorders	—	—	—
Hypoxia	Respiratory, thoracic and mediastinal disorders	—	—	—
Pulmonary Embolism	Respiratory, thoracic and mediastinal disorders	—	—	—
Hypotension	Vascular disorders	—	—	—
Atrial Fibrillation	Cardiac disorders	—	—	—
Cardiac Disorder	Cardiac disorders	—	—	—
Cardiac Failure Congestive	Cardiac disorders	—	—	—
Cardiogenic Shock	Cardiac disorders	—	—	—
Cardiopulmonary Failure	Cardiac disorders	—	—	—

Other adverse events (87 terms — click to expand)

Reaction	System	Part 1 - Bortezomib + Silt…	Part 2 - Bortezomib + Plac…	Part 2 - Bortezomib + Silt…
Neutropenia	Blood and lymphatic system disorders	—	—	—
Thrombocytopenia	Blood and lymphatic system disorders	—	—	—
Peripheral Sensory Neuropathy	Nervous system disorders	—	—	—
Diarrhoea	Gastrointestinal disorders	—	—	—
Anaemia	Blood and lymphatic system disorders	—	—	—
Nausea	Gastrointestinal disorders	—	—	—
Fatigue	General disorders	—	—	—
Leukopenia	Blood and lymphatic system disorders	—	—	—
Neuralgia	Nervous system disorders	—	—	—
Decreased Appetite	Metabolism and nutrition disorders	—	—	—
Constipation	Gastrointestinal disorders	—	—	—
Back Pain	Musculoskeletal and connective tissue disorders	—	—	—
Vomiting	Gastrointestinal disorders	—	—	—
Asthenia	General disorders	—	—	—
Pyrexia	General disorders	—	—	—
Pain in Extremity	Musculoskeletal and connective tissue disorders	—	—	—
Arthralgia	Musculoskeletal and connective tissue disorders	—	—	—
Weight Decreased	Investigations	—	—	—
Dyspnoea	Respiratory, thoracic and mediastinal disorders	—	—	—
Hypophosphataemia	Metabolism and nutrition disorders	—	—	—
Headache	Nervous system disorders	—	—	—
Cough	Respiratory, thoracic and mediastinal disorders	—	—	—
Hypertension	Vascular disorders	—	—	—
Hypokalaemia	Metabolism and nutrition disorders	—	—	—
Bone Pain	Musculoskeletal and connective tissue disorders	—	—	—
Oedema Peripheral	General disorders	—	—	—
Paraesthesia	Nervous system disorders	—	—	—
Nasopharyngitis	Infections and infestations	—	—	—
Insomnia	Psychiatric disorders	—	—	—
Rash	Skin and subcutaneous tissue disorders	—	—	—
Hepatic Function Abnormal	Hepatobiliary disorders	—	—	—
Bronchitis	Infections and infestations	—	—	—
Respiratory Tract Infection	Infections and infestations	—	—	—
Upper Respiratory Tract Infection	Infections and infestations	—	—	—
Dizziness	Nervous system disorders	—	—	—
Renal Impairment	Renal and urinary disorders	—	—	—
Lymphopenia	Blood and lymphatic system disorders	—	—	—
Dyspepsia	Gastrointestinal disorders	—	—	—
Herpes Zoster	Infections and infestations	—	—	—
Hypocalcaemia	Metabolism and nutrition disorders	—	—	—

Most-reported serious reactions: Pneumonia, Sepsis, Anaemia, Bronchopneumonia, Renal Failure Acute, Pulmonary Oedema, Febrile Neutropenia, Thrombocytopenia.

Data from ClinicalTrials.gov NCT00401843 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Targeting the IL-6/JAK/STAT3 signalling axis in cancer.
   Johnson DE, O'Keefe RA, Grandis JR. · · 2018 · cited 2398× · PMID 29405201 · DOI 10.1038/nrclinonc.2018.8
2. Targeting cytokine and chemokine signaling pathways for cancer therapy.
   Yi M, Li T, Niu M, Zhang H, et al · · 2024 · cited 264× · PMID 39034318 · DOI 10.1038/s41392-024-01868-3
3. IL-6 family cytokines: Key inflammatory mediators as biomarkers and potential therapeutic targets.
   Unver N, McAllister F. · · 2018 · cited 178× · PMID 29699936 · DOI 10.1016/j.cytogfr.2018.04.004
4. Clinical Application of Cytokines in Cancer Immunotherapy.
   Qiu Y, Su M, Liu L, Tang Y, et al · · 2021 · cited 76× · PMID 34079226 · DOI 10.2147/dddt.s308578
5. Cancer Cells Exploit Notch Signaling to Redefine a Supportive Cytokine Milieu.
   Colombo M, Mirandola L, Chiriva-Internati M, Basile A, et al · · 2018 · cited 51× · PMID 30154786 · DOI 10.3389/fimmu.2018.01823
6. Network meta-analysis of randomized trials in multiple myeloma: efficacy and safety in relapsed/refractory patients.
   Botta C, Ciliberto D, Rossi M, Staropoli N, et al · · 2017 · cited 44× · PMID 29296961 · DOI 10.1182/bloodadvances.2016003905
7. Monoclonal Antibodies for the Treatment of Multiple Myeloma: An Update.
   Abramson HN. · · 2018 · cited 42× · PMID 30544512 · DOI 10.3390/ijms19123924
8. Monoclonal Antibody Therapies for Hematological Malignancies: Not Just Lineage-Specific Targets.
   Cuesta-Mateos C, Alcaraz-Serna A, Somovilla-Crespo B, Muñoz-Calleja C. · · 2017 · cited 39× · PMID 29387053 · DOI 10.3389/fimmu.2017.01936