Clinical Trial: Pilot Study of Tocilizumab in Patients With Erdheim-Chester Disease

Study Status: Terminated
Recruit Status: Terminated
Study Type: Interventional

Official Title: Open-label, Single-arm, Phase II, Prospective, Pilot Study of Tocilizumab in Patients With Erdheim-Chester Disease

Brief Summary:

The study we propose is a pilot phase II, interventional, treatment, open-label, single-arm, efficacy/safety clinical trial of a 6-month treatment with tocilizumab (8 mg/kg once monthly) in adult patients with extraskeletal Erdheim-Chester disease (ECD). Efficacy will be assessed as the effect of the treatment on the size of the measurable lesions, as evaluated by bidimensional measurements, and by the impact of the treatment on symptom control and on patient quality of life. Safety of the treatment will be determined by the analysis of adverse events and of the relevant safety laboratory parameters.

Secondary objectives of the study will be:

1. to better characterize the mechanisms underlying such disease and the possible response to the treatment. In particular: i) we will investigate the immunophenotypic and histomorphologic features of ECD histiocytes; ii) we will gather gene expression data from peripheral blood immune cells to better characterize their functional status, to define their transcriptional fingerprints and their possible modulation as a result of tocilizumab treatment; iii) we will assess the production of soluble mediators and the expression of activation molecules by monocytes derived from ECD patients, as well as after stimulation with selected inflammatory cytokines; iv) we will investigate the ex vivo and in vitro impact of tocilizumab treatment on those markers, for possible use as a predictor or indicator of response to treatment.
2. to investigate the metabolic pattern in ECD patients before and after tocilizumab treatment as evaluated by fluoro-d-glucose positron emission tomography (FDG-PET) and to verify if it can be an indicator of ECD activity.

Detailed Summary:
Sponsor: Ospedale San Raffaele

Current Primary Outcome:

• Reduction in the dimensions of measurable lesions according to the Response Evaluation Criteria in Solid Tumors (RECIST) criteria [ Time Frame: 6 months ]
• Functional improvement in measurable indexes [ Time Frame: 6 months ]
  Improvement in renal, hypophyseal, and respiratory function or of bone turnover, when altered at baseline
• Variations of patient quality of life [ Time Frame: 6 months ]
  As evaluated by standard questionnaires (HAQ, Short Form (SF)-36)
• Analysis of the adverse events and of the relevant safety laboratory parameters [ Time Frame: 6 months ]
  Monitoring of adverse events, variations in biochemical and hematological tests (full blood count, liver and renal function tests, lipid profile)
• Variations in disease activity as evaluated by FDG-PET imaging [ Time Frame: 0, 2 and 6 months ]

Original Primary Outcome: Same as current

Current Secondary Outcome: Evaluation of soluble factors, receptors and activation molecules involved the accumulation, activation and entrapment of histiocytes possibly associated to a response to the experimental treatment [ Time Frame: 6 months ]

Original Secondary Outcome: Same as current

Information By: Ospedale San Raffaele

Dates:
Date Received: November 12, 2012
Date Started: November 2012
Date Completion:
Last Updated: February 9, 2016
Last Verified: February 2016