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

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

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 Overview

• Status: Not yet recruiting
• Conditions: Mastocytosis
• Intervention / Treatment: Drug: Hydroxychloroquine

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 Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Maella Severino-Freire, MD; Phone Number: +33 05 67 77 81 41; Email: severino-freire.m@chu-toulouse.fr
• Study Contact Backup: Name: Cristina Bulai Livideanu, MD; Phone Number: +33 05 67 77 81 35; Email: livideanu.c@chu-toulouse.fr

Study Locations

• France
  • Toulouse, France, 31059
    • Larrey Hospital - Toulouse University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
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
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
The safety of hydroxychloroquine treatment.	The safety of hydroxychloroquine treatment will be done by evaluation of adverse events	12 month
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

Collaborators and Investigators

• Sponsor: University Hospital, Toulouse
• Investigators: Principal Investigator: Maella Severino-Freire, MD, Toulouse University Hospital

Publications and helpful links

General Publications

• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Anticipated): October 1, 2021
• Primary Completion (Anticipated): January 1, 2024
• Study Completion (Anticipated): January 1, 2024

Study Registration Dates

• First Submitted: October 6, 2021
• First Submitted That Met QC Criteria: October 6, 2021
• First Posted (Actual): October 20, 2021

Study Record Updates

• Last Update Posted (Actual): October 20, 2021
• Last Update Submitted That Met QC Criteria: October 6, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Keywords: hydroxychloroquine; Mastocytosis; mast cell activation symptoms
• Additional Relevant MeSH Terms: Skin Diseases; Immune System Diseases; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Hypersensitivity; Neoplasms, Connective Tissue; Immune Complex Diseases; Mastocytosis; Mastocytosis, Systemic; Mastocytosis, Cutaneous; Mastocytoma; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antirheumatic Agents; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Hydroxychloroquine
• Other Study ID Numbers: RC31/19/0504; 2020-003268-25 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No