Hydroxychloroquine in isolated cutaneous mastocytosis patients or indolent systemic mastocytosis with associated skin involvement patients: proof of concept study

Phase 1

Conditions: mastocytosis
MedDRA version: 21.1Level: PTClassification code 10042949Term: Systemic mastocytosisSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Therapeutic area: Diseases [C] - Skin and Connective Tissue Diseases [C17]

Registration Number: EUCTR2020-003268-25-FR

Lead Sponsor: CHU Toulouse

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

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:
a. Cutaneous pruritus with score = 5 on a VAS scale from 0 to 10
b. Number of flushs / week = 7
4) Skin KIT mutation known
5) Performance scale: OMS/ECOG = 1
6) Woman and man of childbearing age under effective contraception

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 30
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 30

Exclusion Criteria

1) Non-symptomatic mastocytosis and / or without skin involvement
2) Systemic mastocytosis with associated hematologic neoplasm (SM-AHN)
3) Aggressive systemic mastocytosis
4) Mast cell leukemia
5) History of ophthalmic disease and / or cardiac conduction disorders against-indicating the use of hydroxychloroquine
6) Treatment with citalopram, escitalopram, hydroxyzine, domperidone, piperaquine due to the increased risk of ventricular rhythm disorders, especially torsades de pointes
7) Specific anti-tumor treatment (chemotherapy, radiotherapy) of less than 4 weeks before inclusion.
8) Concomitant specific anti-mast cell treatment
9) Inclusion in another trial with an experimental therapeutic molecule
10) Change symptomatic treatment (including dosage) in the 4 weeks preceding the inclusion visit
11) Inability to give informed consent
12) Inability to undergo medical monitoring for geographical, social or psychic
13) Patients with major surgery scheduled in the next two weeks screening
14) Patient without health insurance
15) Pregnancy, Breastfeeding
16) Vulnerable Patient, defined as:
- Esperance survival < 6 months
- Patient with another uncontrolled severe disease
17) Patient under juridical protection

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To evaluate at 12 months the effect of hydroxychloroquine administered at a dose of 6 to 6.5mg / kg / day on mast cell activation symptoms as pruritus and / or flush moderate to severe in patients with isolated cutaneous mastocytosis and / or indolent systemic with associated skin involvement.;Secondary Objective: 1) To assess the objective response rate of mast cell mass at 12 months.<br>2) To assess the effect of hydroxychloroquine on other symptoms of mast cell activation such as: diarrhea, pollakiuria, arthralgia and discomfort at 12 months.<br>3) To assess the tolerance of hydroxychloroquine.<br>4) To assess the association between changes in HCQ blood levels and changes in symptoms of mast cell activation;Primary end point(s): The primary endpoint of this study is the change of mast cell activation symptoms as pruritus and/or flushes between the start of treatment and 12 months later.;Timepoint(s) of evaluation of this end point: 12months after the tratment begining

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): The secondary endpoints are:<br> - The difference on mast cell mass between the start of treatment and 12 months later.<br> - The difference of other mast cell activation symptoms such as diarrhea, pollakiuria, arthralgia and discomfort between the start of treatment and 12 months later.<br> - The safety of hydroxychloroquine treatment.<br> - The correlation of the effectiveness of treatment with the hydroxychloroquine and level of serum HCQ will be performed by the Bland-Altman test.<br>;Timepoint(s) of evaluation of this end point: 12 months after the begining of the treatment and during the treatment

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