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Pilot Study of Tocilizumab in Patients With Erdheim-Chester Disease

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ClinicalTrials.gov Identifier: NCT01727206
Recruitment Status : Terminated
First Posted : November 15, 2012
Last Update Posted : February 10, 2016
Sponsor:
Information provided by (Responsible Party):
Lorenzo Dagna, Ospedale San Raffaele

November 12, 2012
November 15, 2012
February 10, 2016
November 2012
February 2015   (Final data collection date for primary outcome measure)
  • 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 ]
Same as current
Complete list of historical versions of study NCT01727206 on ClinicalTrials.gov Archive Site
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 ]
  • the levels of circulating cytokines and chemokines before, during and after tocilizumab treatment;
  • the immunophenotype and the transcriptional fingerprints of circulating immune cells from ECD patients and their possible modulation as a result of tocilizumab treatment;
  • the pathways involved in the production of interleukin (IL)-6 and IL-6-induced cytokines and chemokines by mononuclear cells obtained from ECD patients;
  • the interference of tocilizumab in vitro on monocyte activation and ex vivo from treated patients, also to evaluate its effect on the profile of circulating cytokines and on the secretory potential of patient-derived monocytes
Same as current
Not Provided
Not Provided
 
Pilot Study of Tocilizumab in Patients With Erdheim-Chester Disease
Open-label, Single-arm, Phase II, Prospective, Pilot Study of Tocilizumab in Patients With Erdheim-Chester Disease

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.
Not Provided
Interventional
Phase 2
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Erdheim-Chester Disease
Drug: Tocilizumab
Other Names:
  • Ro-Actemra
  • Actemra
Experimental: Tocilizumab
Tocilizumab 8 mg/kg intravenously every month for six months
Intervention: Drug: Tocilizumab
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Terminated
3
6
December 2015
February 2015   (Final data collection date for primary outcome measure)

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
Sexes Eligible for Study: All
18 Years and older   (Adult, Older Adult)
No
Contact information is only displayed when the study is recruiting subjects
Italy
 
 
NCT01727206
ECD-TCZ-01
2012-003151-11 ( EudraCT Number )
GR-2009-1594586 ( Other Grant/Funding Number: Italian Ministry of Health )
Yes
Not Provided
Not Provided
Lorenzo Dagna, Ospedale San Raffaele
Ospedale San Raffaele
Not Provided
Principal Investigator: Lorenzo Dagna, MD San Raffaele Scientific Institute
Ospedale San Raffaele
February 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP