Mastocytosis
Conditions
Keywords
Mastocytosis, mast cell activation symptoms, hydroxychloroquine
Brief summary
The treatment of systemic mastocytosis has two main axes: * Control of mast cell activation symptoms and * The control of proliferation (accumulation) of mast cells. There is no standard treatment and no treatment has a marketing authorization for the treatment of monoclonal indolent mastocytosis.
Detailed description
Mastocytosis is an orphan disease related to the accumulation and / or the proliferation of abnormal mast cells in different tissues. In adults, a classic distinction is made between isolated cutaneous forms (10 to 15%) and systemic forms (85 to 90%). The treatment of systemic mastocytosis has two main axes: * Control of mast cell activation symptoms and * The control of proliferation (accumulation) of mast cells. There is no standard treatment and no treatment has a marketing authorization for the treatment of monoclonal indolent mastocytosis.
Interventions
DRUGHydroxychloroquine
Patients will be treated by hydroxychloroquine at a dose of 6 to 6.5mg/kg/day during 12 month
Sponsors
University Hospital, Toulouse
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Age \> 18 years 2. Isolated Cutaneous mastocytosis or indolent systemic mastocytosis with associated skin lesions defined according to WHO criteria (and / or international standards for cutaneous mastocytosis) 3. Patient with at least one disability defined by the presence of the following symptoms assessed as moderate to severe: 1. Cutaneous pruritus with score ≥ 5 on a VAS scale from 0 to 10 2. Number of flushes / week ≥ 7 4. Skin KIT mutation known 5. Performance scale: OMS/ECOG ≤ 1 6. Woman and man of childbearing age\* under effective contraception during all the treatment by hydroxychloroquine, until 8 months after its cessation
Exclusion criteria
* Non-symptomatic mastocytosis and / or without skin involvement * Advanced Systemic mastocytosis * History of ophthalmic disease and / or cardiac conduction disorders, in particular the prolongation of the QT interval as well as the risk factors for prolongation of the QT interval, such as heart disease (heart failure, myocardial infarction), pro-arrhythmic conditions (eg bradycardia \<50 bpm), history of ventricular dysrhythmias, uncorrected hypokalemia and / or hypomagnesemia, concomitant treatment with interval prolonging agents QTagainst-indicating the use of hydroxychloroquine * Treatment with citalopram, escitalopram, hydroxyzine, domperidone, piperaquine due to the increased risk of ventricular rhythm disorders, especially torsades de pointes * Specific anti-tumor treatment (chemotherapy, radiotherapy) of less than 4 weeks before inclusion. * Concomitant specific anti-mast cell treatment * Contre-indication(s) to XYLOCAINE 10 mg/ml ADRENALINE 0,005 mg/ml, injectable solution: Known hypersensitivity to chlorhydrate de lidocaïne, to amide-type local anaesthetics or one of its excipients (sulfites), patients suffering from recurring porphyrias, coronary insufficiency, ventricular rhythm disorders, severe arterial hypertension, obstructive cardiomyopathy, hyperthyroidism. * Inclusion in another trial with an experimental therapeutic molecule * Change symptomatic treatment (including dosage) in the 4 weeks preceding the inclusion visit * Moderate to severe renal or hepatic failure or diabetes * History of organ transplant * Inability to give informed consent * Inability to undergo medical monitoring for geographical, social or psychic * Patients with major surgery scheduled in the next two weeks screening * Patient without health insurance * Pregnancy, Breastfeeding * Vulnerable Patient, defined as: * Esperanzae survival \< 6 months * Patient with another uncontrolled severe disease * Patient under juridical protection
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change of mast cell activation symptoms | 12 month | The primary endpoint of this study is the change of mast cell activation symptoms as pruritus between the start of treatment and 12 months later. Skin pruritus will be assessed by the visual analogue scale from 0 to 10 at each visit. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Difference on skin mast cell burden - mast cells/mm² | 12 month | The difference on mast cell burden between the start of treatment and 12 months later will be assessed by variation of the number of mast cells / mm² identified on the skin biopsies. |
| Difference of mast cell activation symptoms : diarrhea | 12 month | The difference of diarrhea between the start of treatment and 12 months later evaluated by the absolute number of stools / day for diarrhea |
| Difference of mast cell activation symptoms : pollakiuria | 12 month | The difference of pollakiuria between the start of treatment and 12 months later assessed by the absolute number of urinations / day for pollakiuria. |
| Difference on mast cell burden - serum tryptase level | 12 month | The difference on mast cell burden between the start of treatment and 12 months later will be evaluated by variation of the level serum tryptase l expressed in μg / L. |
| Difference of mast cell activation symptoms : discomfort | 12 month | The difference of discomfort between the start of treatment and 12 months later evaluated by the absolute number of faintness / week |
| The safety of hydroxychloroquine treatment. | 12 month | The safety of hydroxychloroquine treatment will be done by evaluation of adverse events |
| effectiveness of treatment | 12 month | The correlation between the efficacy of treatment with the hydroxychloroquine and level of serum HCQ will be performed by the Bland-Altman test. |
| Difference of mast cell activation symptoms : arthralgia | 12 month | The difference of arthralgia between the start of treatment and 12 months later evaluated by the absolute number of painful joints / day and the intensity of joint pain assessed by the visual analogue scale from 0 to 10 for arthralgia. |
Countries
France
Contacts
Primary ContactMaella Severino-Freire, MD
Backup ContactCristina Bulai Livideanu, MD
Outcome results
None listed