Patient case: 19-year-old female with long QT syndrome; genetic feature: KCNH2

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

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.


Eligibility: Inclusion Criteria:
  -  patients >= 18 years of age able to understand and sign an informed consent;
  -  histologically proven diagnosis of Erdheim-Chester disease ;
  -  an advanced disease not limited to the skeleton, with at least one measurable lesion;
  -  if females of childbearing potential, a negative pregnancy test and willingness to adhere to a highly effective contraceptive method of birth control for the duration of the study;
  Exclusion Criteria:
  -  history of hypersensitivity to tocilizumab or to any of the excipients;
  ￼- severe infections requiring hospitalization or antibiotic therapy in the 30 days before the enrollment in the study;
  -  active tuberculosis, listeriosis, histoplasmosis, sepsis, abscesses, opportunistic infections; active hepatitis B or C virus infection;
  -  past history of tuberculosis (as documented by a positive purified protein derivative (PPD) skin test and/or a positive Quantiferon test and/or a chest X- ray), in the absence of a documented and appropriate administration of a specific treatment for latent tuberculosis;
  -  history of human immunodeficiency virus (HIV) infection;
  -  past history (< 5 years before enrollment) of a lymphoproliferative disorder or of a solid cancer (excluding cured basal cell or squamous cell carcinoma of the skin);
  -  moderate or severe heart failure (NYHA class III/IV), uncontrolled diabetes mellitus or other diseases that -according to the physician in charge of the protocol- may be of harm to the patient, if he/she would enroll in the study;
  -  history of alcohol and/or drug abuse;
  -  prior treatment with alkylating drugs (chlorambucil, cyclophosphamide);
  -  serum creatinine > 1.6 mg/dL in female patients or > 1.9 mg/dL in male patients, aspartate aminotransferase and/or alanine aminotransferase > 3 x upper limit of normal ; platelet < 100.000/fL; hemoglobin < 8.5 g/dL; white blood cell count < 1000/fL; lymphocyte < 500/fL; total bilirubin > 2.0 mg/dL

Relevance to patient case: not relevant