Pilot Study of Tocilizumab in Patients With Erdheim-Chester Disease

This study is currently recruiting participants. (see Contacts and Locations)
Verified November 2012 by Ospedale San Raffaele
Sponsor:
Information provided by (Responsible Party):
Lorenzo Dagna, Ospedale San Raffaele
ClinicalTrials.gov Identifier:
NCT01727206
First received: November 12, 2012
Last updated: NA
Last verified: November 2012
History: No changes posted
  Purpose

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.

Condition Intervention Phase
Erdheim-Chester Disease
Drug: Tocilizumab
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Open-label, Single-arm, Phase II, Prospective, Pilot Study of Tocilizumab in Patients With Erdheim-Chester Disease

Resource links provided by NLM:


Further study details as provided by Ospedale San Raffaele:

Primary Outcome Measures:
  • Reduction in the dimensions of measurable lesions according to the Response Evaluation Criteria in Solid Tumors (RECIST) criteria [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Functional improvement in measurable indexes [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    • 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


Estimated Enrollment: 6
Study Start Date: November 2012
Estimated Study Completion Date: November 2014
Estimated Primary Completion Date: November 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Tocilizumab
Tocilizumab 8 mg/kg intravenously every month for six months
Drug: Tocilizumab
Other Names:
  • Ro-Actemra
  • Actemra

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01727206

Contacts
Contact: Lorenzo Dagna, MD +39022643 ext 6096 lorenzo.dagna@unisr.it

Locations
Italy
San Raffaele Hospital Recruiting
Milano, Italy, 20132
Sub-Investigator: Barbara Guglielmi, MD         
Sponsors and Collaborators
Ospedale San Raffaele
Investigators
Principal Investigator: Lorenzo Dagna, MD San Raffaele Scientific Institute
  More Information

No publications provided

Responsible Party: Lorenzo Dagna, Professor, Ospedale San Raffaele
ClinicalTrials.gov Identifier: NCT01727206     History of Changes
Other Study ID Numbers: ECD-TCZ-01, 2012-003151-11, GR-2009-1594586
Study First Received: November 12, 2012
Last Updated: November 12, 2012
Health Authority: Italy: The Italian Medicines Agency
Italy: National Institute of Health

Keywords provided by Ospedale San Raffaele:
Erdheim-Chester disease
Tocilizumab
Treatment
Phase II

Additional relevant MeSH terms:
Erdheim-Chester Disease
Histiocytosis, Non-Langerhans-Cell
Histiocytosis
Lymphatic Diseases

ClinicalTrials.gov processed this record on August 28, 2014