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STUDY DESIGN

study design

Patients (n=79) were randomised to SYLVANT® (n=53) or placebo (n=26) and treated until treatment failure (disease progression based on increase in symptoms, radiologic progression or deterioration in performance status) or unacceptable toxicity (Figure 6).6,7

KEY INCLUSION AND EXCLUSION CRITERIA

For inclusion, patients had to:6-8

  • Be ≥ 18 years of age
  • Have multicentric Castleman’s disease (based on patient history, physical examination, assessment of laboratory abnormalities, pathological diagnosis, and radiological imaging, and a histologically confirmed diagnosis using pre-specified criteria by a central pathology laboratory from an excisional lymph node taken before enrolment)
  • Have measurable disease (not limited to cutaneous lesions)
  • Have grade ≥1 disease symptoms (according to the National Cancer Institute Common Terminology Criteria for Adverse Events v 4.0)
  • Have ECOG score 0–2

Patients could be newly diagnosed or previously treated, except those who had previously received IL-6 targeted treatment.

Patients were excluded if they:

  • Were HIV-seropositive
  • Evidence of human herpesvirus-8 infection (by quantitative PCR in plasma by a central laboratory)
  • Other clinically significant infections, including hepatitis B or C
  • Had a history of, or concurrent lymphoma

ENDPOINTS

The primary endpoint was the percentage of patients who achieved durable tumour and symptomatic response (as assessed by an independent radiology review) defined as either a complete response or a partial response for at least 18 weeks. There was no validated criteria to evaluate iMCD. As iMCD is lymphoproliferative, the modified Cheson criteria were used (as they can be used to evaluate lymph nodes), however the criteria were adjusted to include the assessment of cutaneous lesions caused by iMCD.

Symptoms were scored using the MCD-related overall symptom score, which is the sum of the severity grades of MCD-related signs and symptoms. The percentage change from baseline in MCD-related signs and symptoms and MCD-related overall symptom score at each cycle was calculated.6 A complete response was defined as a 100% reduction from baseline in the MCD-related overall symptoms score.

Key secondary endpoints included:7,8

  • Median duration of durable tumour and symptomatic response
  • Tumour response rate (percentage of participants who achieved complete response or partial tumour response)
  • Time to tumour response (by independent review for responders)
  • Durable symptomatic response rate
  • Complete symptoms response rate
  • Time to durable symptomatic response
  • Time to treatment failure
  • Percentage of patients who achieved ≥ 15 g/L haemoglobin at week 13
  • Percentage of patients who discontinued corticosteroids
  • Overall survival at 1 year
  • Patient-reported outcomes

Figure 6: Study Design

Figure 6: Study design

Figure 6: Study Design

Study Design Back button

BACK

 

*  Treatment failure was defined as sustained increase in grade ≥2 disease-related symptoms persisting ≥3 weeks; new disease-related grade ≥3 symptoms; sustained >1 paint increase in ECOG-PS persisting for ≥3 weeks; radiological progression by modified Cheson criteria or initiation of another treatment for iMCD. At 1st treatment failure, patients in the placebo arm could crossover to receive open-label Sylvant® (+ best supportive care) until second treatment failure.

References

  1. SYLVANT® EU Summary of Product Characteristics (Sept 2019).
  2. LLC Clinical Trial. A Study to Evaluate the Efficacy and Safety of CNTO328 Plus Best Supportive Care in Multicentric Castleman’s Disease 2018 [Available from: https://clinicaltrials.gov/ct2/show/NCT01024036?term=siltuximab&recrs=e&phase=1&draw=2&rank=3.
  3. Van Rhee F, Wong RS, Munshi N, Rossi JF, Ke XY, Fossa A, et al. Siltuximab for multicentric Castleman’s disease: a randomised, double-blind, placebo-controlled trial. Lancet Oncol. 2014;15(9):966-74.
  4. Van Rhee F, Casper C, Voorhees PM, Fayad LE, Gibson D, Kanhai K, et al. Long-term safety of siltuximab in patients with idiopathic multicentric Castleman disease: a prespecified, open-label, extension analysis of two trials. Lancet Haematol. 2020;7(3):e209-e217.

EUSA Sylvant © 2021 EUSA Pharma      Date of prep: November 2021    GL-SIL-2100103

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