Erdheim-Chester DiseasePhase 2NCT01727206
Pilot Study of Tocilizumab in Patients With Erdheim-Chester Disease
A Phase 2 study testing Tocilizumab in people with Erdheim-Chester Disease, run by Ospedale San Raffaele at 1 site in Italy.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Erdheim-Chester Disease
- What is being tested?
- Tocilizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 3 participants
- Where
- 1 siteItaly
- Study dates
- Nov 2012to Dec 2015
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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;
Who cannot join
- 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);
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- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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:
- 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.
- 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.
- Conditions
- Erdheim-Chester Disease
- Being tested
- Tocilizumab
- Keywords
- Erdheim-Chester disease, Tocilizumab, Treatment, Phase II
- Medical subject headings
- Erdheim-Chester Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TocilizumabDrug
Also called Ro-Actemra, Actemra
| Study group | Role | What they receive |
|---|---|---|
| Tocilizumab | Experimental | Tocilizumab 8 mg/kg intravenously every month for six months Receives: Drug: Tocilizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Reduction in the dimensions of measurable lesions according to the Response Evaluation Criteria in Solid Tumors (RECIST) criteria
Measured: 6 months
Functional improvement in measurable indexes
Improvement in renal, hypophyseal, and respiratory function or of bone turnover, when altered at baseline
Measured: 6 months
Variations of patient quality of life
As evaluated by standard questionnaires (HAQ, Short Form (SF)-36)
Measured: 6 months
Analysis of the adverse events and of the relevant safety laboratory parameters
Monitoring of adverse events, variations in biochemical and hematological tests (full blood count, liver and renal function tests, lipid profile)
Measured: 6 months
Variations in disease activity as evaluated by FDG-PET imaging
Measured: 0, 2 and 6 months
Secondary outcomes (1)
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
- 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
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Nov 2012 (estimated)
- Study startNov 2012
- Primary completionFeb 2015
- Study completionDec 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Erdheim-Chester DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 3 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ospedale San Raffaele
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Lorenzo Dagna, Ospedale San Raffaele
- Investigators
- Lorenzo Dagna, MD, Principal investigator, San Raffaele Scientific Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01727206
- Sponsor's protocol ID
- ECD-TCZ-01
- Other IDs
- 2012-003151-11, GR-2009-1594586
- Status last verified
- Feb 2016
- First submitted
- 12 Nov 2012
- Last updated
- 10 Feb 2016
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 10 Feb 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Open-label, Single-arm, Phase II, Prospective, Pilot Study of Tocilizumab in Patients With Erdheim-Chester Disease
- ClinicalTrials.gov ID
- NCT01727206
- Acronym / sponsor ID
- ECD-TCZ-01
- Conditions
- Erdheim-Chester Disease
- Keywords
- Erdheim-Chester disease, Tocilizumab, Treatment, Phase II
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 3 participants (actual)
- Lead sponsor
- Ospedale San RaffaeleUniversity, hospital or other
- Study start
- Nov 2012
- Primary completion
- Feb 2015 (actual)
- Study completion
- Dec 2015 (actual)
- First posted
- 15 Nov 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- 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.
- 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Tocilizumab | Experimental | Drug: TocilizumabTocilizumab 8 mg/kg intravenously every month for six months |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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;
Key exclusion criteria (10 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TocilizumabAlso: Ro-Actemra, Actemra | Drug | Tocilizumab |
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
1 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
Results and safety
The study was stopped early. Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Feb 2016.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Lorenzo Dagna, MD principal investigator
San Raffaele Scientific Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Tocilizumab in people with Erdheim-Chester Disease, run by Ospedale San Raffaele at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 10 Feb 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early. Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the 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). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Feb 2016.