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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Centre Hospitalier Universitaire De Toulouse

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Skin and Connective Tissue Diseases [C17]

Trial duration

18 Nov 2021 → ongoing

Decision date (initial)

2024-10-22

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

External identifiers

EU CT number

2024-518594-33-00

EudraCT number

2020-003268-25

ClinicalTrials.gov

NCT05084872

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

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 objectives 4

1. 1) To assess the objective response rate of mast cell mass at 12 months.
2. 2) To assess the effect of hydroxychloroquine on other symptoms of mast cell activation such as: diarrhea, pollakiuria, arthralgia and discomfort at 12 months.
3. 3) To assess the tolerance of hydroxychloroquine.
4. 4) To assess the association between changes in HCQ blood levels and changes in symptoms of mast cell activation

Conditions and MedDRA coding

mastocytosis

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

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 ≥ 3 on a VAS scale from 0 to 10 b. Number of flushs / week ≥ 5
4. Skin KIT mutation known
5. Performance scale: OMS/ECOG ≤ 1
6. Woman and man of childbearing age under effective contraception during treatment with hydroxychloroquine and up to 8 months after stopping it

Exclusion criteria 17

1. Non-symptomatic mastocytosis and / or without skin involvement
2. Systemic mastocytosis with associated hematologic neoplasm (SMAHN)
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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 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.

Secondary endpoints 4

1. - The difference on mast cell mass between the start of treatment and 12 months later
2. The difference of other mast cell activation symptoms such as diarrhea, pollakiuria, arthralgia and discomfort between the start of treatment and 12 months later.
3. Tolerance by clinical examination and if necessary paraclinical according to the investigator's decision; tolerance will be assessed during the study period
4. The correlation of the effectiveness of treatment with the hydroxychloroquine and level of serum HCQ

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Centre Hospitalier Universitaire De Toulouse

Sponsor organisation

Centre Hospitalier Universitaire De Toulouse

Address

2 Rue Viguerie

City

Toulouse

Postcode

31300

Country

France

Scientific contact point

Organisation

Centre Hospitalier Universitaire De Toulouse

Contact name

Christina LIVIDEANU

Public contact point

Organisation

Centre Hospitalier Universitaire De Toulouse

Contact name

Florine LEGAY

Locations

1 EU/EEA country · 2 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 9 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications