Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12613001321730
Ethics application status
Approved
Date submitted
26/11/2013
Date registered
28/11/2013
Date last updated
28/11/2013
Type of registration
Retrospectively registered

Titles & IDs
Public title
Sirolimus plus prednisone for the treatment of Erdheim-Chester Disease: a pilot study
Scientific title
Prospective non randomized pilot study using Sirolimus and Prednisone to induce remission in patients with Erdheim-Chester Disease.
Secondary ID [1] 283645 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Erdheim-Chester disease 290587 0
Condition category
Condition code
Inflammatory and Immune System 290979 290979 0 0
Other inflammatory or immune system disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Prednisone is given orally at the initial dose of 0.75 mg/kg/day for 1 month, tapered to 2.5-5 mg/day over 6 months.
Rapamycin is given orally at a daily dose of 2-4 mg, with a target trough plasmatic level of 8-12 ng/mL.
The minimum duration of treatment to assess response to therapy is 6 months. If disease stabilisation or remission is achieved, we plan to continue treatment for an overall duration of 2 years. After the end of year 2, the decision as to whether treatment has to be continued or stopped is left at the discretion of the treating clinician and the patient.
The response to treatment and the monitoring for side effects is assessed by means of clinical examination and appropriate laboratory and imaging studies (CT, MRI, PET/CT, bone scintigraphy).
To monitor the adherence to sirolimus therapy and to modulate sirolimus dose, we evaluate plasma concentration of sirolimus (trough levels) which must be between 8 and 12 ng/mL.
Intervention code [1] 288343 0
Treatment: Drugs
Comparator / control treatment
Non randomized study. No controls.
Control group
Uncontrolled

Outcomes
Primary outcome [1] 290958 0
Mortality
Timepoint [1] 290958 0
Three years follow-up
Primary outcome [2] 290959 0
Evaluation of disease progression, regression or stabilization.

The response to treatment is assessed by means of clinical examination and appropriate laboratory (white blood cell count, hemoglobin, ESR, CRP, renal, hepatic, lipid and glucose profiles, urinalysis, etc.) and imaging studies (CT, MRI, PET/CT, bone scintigraphy).
Timepoint [2] 290959 0
One year follow-up
Secondary outcome [1] 305677 0
Treatment related toxicity

This will be assessed regularly at the planned study visits by means of physical examination, laboratory and appropriate imaging studies. In particular, we will assess prednisone-and sirolimus-related side effects, such as dyslipidemia, diabetes, osteoporosis, drug-related pneumonia, effusions, edema.
Timepoint [1] 305677 0
At every year of follow-up for up to 5 years

Eligibility
Key inclusion criteria
- Diagnosis of Erdheim-Chester with systemic involvement
- Active disease (newly diagnosed progressive disease in patients undergoing other treatments)
Minimum age
18 Years
Maximum age
75 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Concurrent active malignancies or serious infections
- Hypersensitivity to sirolimus and/or prednisone and/or contraindications to their use (uncontrolled diabetes
mellitus, severe osteoporosis with previous fractures)
- Proteinuria > 1g/24h
- Recent major surgery and/or post-surgical complications
- Pregnancy
- Patients partecipating in other trials

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 2
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Date of first participant enrolment
Anticipated
1/12/2007
Actual
1/12/2007
Date of last participant enrolment
Anticipated
Actual
14/06/2013
Date of last data collection
Anticipated
Actual
Sample size
Target
10
Accrual to date
Final
Recruitment outside Australia
Country [1] 5654 0
Italy
State/province [1] 5654 0

Funding & Sponsors
Funding source category [1] 288330 0
University
Name [1] 288330 0
Department of Clinical and Experimental Medicine, University of Parma
Country [1] 288330 0
Italy
Primary sponsor type
University
Name
University of Parma, Department of Clinical and Experiment Medicine
Address
Department of Clinical and Experimental Medicine
Universital Hospital of Parma
via Gramsci 14, 43126
Parma (PR)
Italy
Country
Italy
Secondary sponsor category [1] 287046 0
None
Name [1] 287046 0
Address [1] 287046 0
Country [1] 287046 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 290222 0
Comitato Etico per la provincia di Parma
Ethics committee address [1] 290222 0
Ethics committee country [1] 290222 0
Italy
Date submitted for ethics approval [1] 290222 0
Approval date [1] 290222 0
12/11/2007
Ethics approval number [1] 290222 0

Summary
Brief summary
The main purpose of our study is to identify an effective and tolerable treatment for Erdheim-Chester disease.
To date, various regimens have been used with variable results and often burdened by severe toxic effects. On the basis of rapamycin characteristics and of the information available about this disease, we think Sirolimus (one of the commercially available forms of rapamycin) associated with steroids, such as prednisone, could be an alternative therapeutic approach for this disease.
Prednisone is given orally at the initial dose of 0.75 mg/kg/day for 1 month, tapered to 2.5-5 mg/day over 6 months.
Rapamycin is given orally at a daily dose of 2-4 mg, with a target trough level of 8-12 ng/mL.
The minimum duration of treatment to assess response to therapy is 6 months; if disease stabilisation or remission is achieved, the treatment is continued usually until the end of the second year; then, the treatment can be continued or stopped at the discretion of the treating clinician.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 44510 0
Dr Augusto Vaglio
Address 44510 0
Unit of Nephrology,
University Hospital of Parma,
Via Gramsci, 14
43126 Parma
Country 44510 0
Italy
Phone 44510 0
+39 0521 033176
Fax 44510 0
Email 44510 0
augusto.vaglio@virgilio.it
Contact person for public queries
Name 44511 0
Dr Augusto Vaglio
Address 44511 0
Unit of Nephrology,
University Hospital of Parma,
Via Gramsci, 14
43126 Parma
Country 44511 0
Italy
Phone 44511 0
+39 0521 033176
Fax 44511 0
Email 44511 0
augusto.vaglio@virgilio.it
Contact person for scientific queries
Name 44512 0
Dr Augusto Vaglio
Address 44512 0
Unit of Nephrology,
University Hospital of Parma,
Via Gramsci, 14
43126 Parma
Country 44512 0
Italy
Phone 44512 0
+39 0521 033176
Fax 44512 0
Email 44512 0
augusto.vaglio@virgilio.it

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided


Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseCardiovascular manifestations of Erdheim-Chester disease.2015
EmbaseSirolimus plus prednisone for Erdheim-Chester disease: An open-label trial.2015https://dx.doi.org/10.1182/blood-2015-01-620377
Dimensions AIRecurrent RAS and PIK3CA mutations in Erdheim-Chester disease2014https://doi.org/10.1182/blood-2014-04-570937
N.B. These documents automatically identified may not have been verified by the study sponsor.