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

Sponsor

University Hospital, Toulouse (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05084872

Collaborator

(none)

Enrollment

Location

Arm

Anticipated Duration (Months)

1.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Mastocytosis	Drug: Hydroxychloroquine	Phase 2/Phase 3

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

30 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Hydroxychloroquine in Isolated Cutaneous Mastocytosis Patients or Indolent Systemic Mastocytosis With Associated Skin Involvement Patients: Proof of Concept Study

Anticipated Study Start Date :

Oct 1, 2021

Anticipated Primary Completion Date :

Jan 1, 2024

Anticipated Study Completion Date :

Jan 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment Patients will be treated by hydroxychloroquine at a dose of 6 to 6.5mg/kg/day	Drug: Hydroxychloroquine Patients will be treated by hydroxychloroquine at a dose of 6 to 6.5mg/kg/day during 12 month

Arm

Intervention/Treatment

Experimental: Treatment

Patients will be treated by hydroxychloroquine at a dose of 6 to 6.5mg/kg/day

Drug: Hydroxychloroquine

Patients will be treated by hydroxychloroquine at a dose of 6 to 6.5mg/kg/day during 12 month

Outcome Measures

Primary Outcome Measures

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.
Change of mast cell activation symptoms [12 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

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 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 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.
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Age > 18 years
Isolated Cutaneous mastocytosis or indolent systemic mastocytosis with associated skin lesions defined according to WHO criteria (and / or international standards for cutaneous mastocytosis)
Patient with at least one disability defined by the presence of the following symptoms assessed as moderate to severe:
Cutaneous pruritus with score ≥ 5 on a VAS scale from 0 to 10
Number of flushes / week ≥ 7
Skin KIT mutation known
Performance scale: OMS/ECOG ≤ 1
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