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Hydroxychloroquine in Isolated Cutaneous Mastocytosis Patients or Indolent Systemic Mastocytosis With Associated Skin Involvement Patients

Phase 2
Conditions
Mastocytosis
Interventions
Registration Number
NCT05084872
Lead Sponsor
University Hospital, Toulouse
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.

Recruitment & Eligibility

Status
UNKNOWN
Sex
All
Target Recruitment
30
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
TreatmentHydroxychloroquinePatients will be treated by hydroxychloroquine at a dose of 6 to 6.5mg/kg/day
Primary Outcome Measures
NameTimeMethod
Change of mast cell activation symptoms12 month

The primary endpoint of this study is the change of mast cell activation symptoms as flushes between the start of treatment and 12 months later. The skin flush will be evaluated according to the absolute number of flushes / week at each visit

Secondary Outcome Measures
NameTimeMethod
Difference on mast cell burden - serum tryptase level12 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 : arthralgia12 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.

Difference on skin mast cell burden - mast cells/mm²12 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 : diarrhea12 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 : pollakiuria12 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 of mast cell activation symptoms : discomfort12 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 treatment12 month

The correlation between the efficacy of treatment with the hydroxychloroquine and level of serum HCQ will be performed by the Bland-Altman test.

Trial Locations

Locations (1)

Larrey Hospital - Toulouse University Hospital

🇫🇷

Toulouse, France

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