Recruitment in a randomized, double-blind, placebo-controlled study to assess siltuximab (CNTO 328), an anti-IL-6 monoclonal antibody, in patients with multicentric Castleman’s disease.

Abstract

TPS8117 Background: Multicentric Castleman’s disease (MCD) is a rare lymphoproliferative disorder in which dysregulated production of interleukin (IL)-6 results in lymph node enlargement and debilitating symptoms, including systemic inflammatory manifestations (eg, fever, fatigue, weight loss), autoimmune phenomena, and markedly abnormal laboratory findings (eg, anemia, hyper-γ-globulinemia, hypoalbuminemia, thrombocytosis, increases in acute-phase proteins such as CRP, ESR, fibrinogen). There is currently no approved systemic treatment for MCD in the US or EU. Siltuximab (CNTO 328) is a chimeric mAb with high affinity for soluble IL-6. In a previous phase 1 study, high objective tumor response rate (64%) has been observed in patients with MCD (van Rhee F et al. Blood 2008;112:1008), and the long-term safety profile looks favourable (Kurzrock R et al. Blood 2011;118:3959). These results have prompted a randomized, double-blind, placebo-controlled study to definitively assess the efficacy and safety of siltuximab in combination with best supportive care (BSC) compared with BSC in patients with MCD. Methods: Eligibility includes HIV- and HHV-8-negative, symptomatic, measurable MCD patients. Patients with prior lymphoma or prior exposure to treatment targeting IL-6 or its receptor are excluded. Patients can be enrolled when receiving stable doses of corticosteroids (<1 mg/kg/d of prednisone or equivalent). Patients will be randomized in a 1:2 ratio to placebo + BSC or to 11 mg/kg siltuximab + BSC and will receive siltuximab/placebo in a 1-hour IV infusion every 3 weeks. The primary objective is to evaluate durable tumor and symptomatic response in the intent-to-treat population. Secondary objectives include additional efficacy measures, safety, patient reported outcomes, and pharmacologic assessment. Status: 67/78 patients have been randomly assigned. This is the first randomized, placebo-controlled study to be conducted in MCD. The rarity of the disease has posed unique challenges, and various enrollment strategies have been successfully implemented, with projected completion of enrollment in March 2012.