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

Mastocytosis Clinical Trial

— HCQMa  

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05084872
• Other study ID #: RC31/19/0504
• Secondary ID: 2020-003268-25
• Status: Not yet recruiting
• Phase: Phase 2/Phase 3
• Start date: October 2021
• Est. completion date: January 2024

Study information

• Verified date: October 2021
• Source: University Hospital, Toulouse
• Contact: Maella Severino-Freire, MD
• Phone: 05 67 77 81 41
• Email: severino-freire.m[@]chu-toulouse.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Not yet recruiting
• Enrollment: 30
• Est. completion date: January 2024
• Est. primary completion date: January 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Mastocytosis

Intervention

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

Locations

Country	Name	City	State
France	Larrey Hospital - Toulouse University Hospital	Toulouse

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Toulouse

Country where clinical trial is conducted

France, 

References & Publications (2)

Fradet M, Negretto M, Tournier E, Laurent C, Apoil PA, Evrard S, Degboe Y, Del Mas V, Lamant L, Dubreuil P, Laroche M, Mailhol C, Hermine O, Paul C, Bulai Livideanu C. Frequency of isolated cutaneous involvement in adult mastocytosis: a cohort study. J Eur Acad Dermatol Venereol. 2019 Sep;33(9):1713-1718. doi: 10.1111/jdv.15638. Epub 2019 May 17. — View Citation

Severino M, Chandesris MO, Barete S, Tournier E, Sans B, Laurent C, Apoil PA, Lamant L, Mailhol C, Laroche M, Fraitag S, Hanssens K, Dubreuil P, Hermine O, Paul C, Bulai Livideanu C. Telangiectasia macularis eruptiva perstans (TMEP): A form of cutaneous mastocytosis with potential systemic involvement. J Am Acad Dermatol. 2016 May;74(5):885-91.e1. doi: 10.1016/j.jaad.2015.10.050. Epub 2016 Feb 19. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change of mast cell activation symptoms	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.	12 month
Primary	Change of mast cell activation symptoms	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	12 month
Secondary	Difference on mast cell burden - serum tryptase level	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.	12 month
Secondary	Difference on skin mast cell burden - mast cells/mm²	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.	12 month
Secondary	Difference of mast cell activation symptoms : diarrhea	The difference of diarrhea between the start of treatment and 12 months later evaluated by the absolute number of stools / day for diarrhea	12 month
Secondary	Difference of mast cell activation symptoms : pollakiuria	The difference of pollakiuria between the start of treatment and 12 months later assessed by the absolute number of urinations / day for pollakiuria.	12 month
Secondary	Difference of mast cell activation symptoms : arthralgia	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.	12 month
Secondary	Difference of mast cell activation symptoms : discomfort	The difference of discomfort between the start of treatment and 12 months later evaluated by the absolute number of faintness / week	12 month
Secondary	The safety of hydroxychloroquine treatment.	The safety of hydroxychloroquine treatment will be done by evaluation of adverse events	12 month
Secondary	effectiveness of treatment	The correlation between the efficacy of treatment with the hydroxychloroquine and level of serum HCQ will be performed by the Bland-Altman test.	12 month