Evaluation of Hydroxychloroquine Sulfate in Patients with Isolated Cutaneous Mastocytosis or Indolent Systemic Mastocytosis with Skin Involvement

The primary objective of this study is to evaluate the effect of **hydroxychloroquine** administered at a dose of 6 to 6.5 mg/kg/day on symptoms of mast cell activation, specifically pruritus and/or flush of moderate to severe intensity, in patients with isolated cutaneous mastocytosis and/or indolent systemic mastocytosis with associated skin involvement over a 12-month period. This is clinically relevant as it aims to address the symptomatic burden in these patients, potentially improving their quality of life.

Secondary objectives include:

• Assessing the objective response rate of mast cell mass at 12 months.
• Evaluating the effect of hydroxychloroquine on other symptoms of mast cell activation such as diarrhea, pollakiuria, arthralgia, and discomfort at 12 months.
• Assessing the tolerance of hydroxychloroquine.
• Evaluating the association between changes in hydroxychloroquine blood levels and changes in symptoms of mast cell activation.

The clinical trial focuses on evaluating the effect of hydroxychloroquine on **mastocytosis** symptoms, specifically targeting individuals with isolated cutaneous mastocytosis or indolent systemic mastocytosis with associated skin involvement. The study population includes both male and female participants over the age of 18, with no vulnerable populations selected. Participants are required to have a known skin KIT mutation and must exhibit at least one disability, such as moderate to severe cutaneous pruritus or frequent flushing. The trial does not specify the total number of participants, as this information was not provided by the sponsor. Participants are expected to maintain effective contraception during and for eight months following the treatment period. The selection criteria ensure that individuals have a performance scale of OMS/ECOG ≤ 1, indicating a generally good health status. Lifestyle factors such as diet and physical activity are not specified as part of the trial's considerations.

The clinical trial is designed to evaluate the effect of **hydroxychloroquine** on mast cell activation symptoms in patients with isolated cutaneous mastocytosis or indolent systemic mastocytosis with associated skin involvement. This study is a randomized, double-blind, controlled trial with an estimated duration of 12 months for each participant. The trial will assess the primary endpoint of changes in symptoms such as pruritus and flushes over a 12-month period, with secondary endpoints including changes in mast cell mass and other symptoms like diarrhea and arthralgia, as well as the safety and serum levels of hydroxychloroquine.

Participants will undergo a sequence of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age over 18 years, presence of specific symptoms, and known skin KIT mutation. Following the screening, participants will be randomized to receive either the active treatment or a control. Regular follow-up visits will be scheduled to monitor the participants' health, adherence to the treatment regimen, and any adverse events. The end-of-study visit will occur at the conclusion of the 12-month treatment period, where final assessments will be conducted to evaluate the primary and secondary endpoints.

The expected length of participant involvement is approximately 12 months, with conditions for early termination including significant adverse reactions, non-compliance with the study protocol, or withdrawal of consent. The trial aims to provide valuable insights into the therapeutic potential of hydroxychloroquine for managing symptoms associated with mastocytosis, contributing to the broader understanding of treatment options for this condition.

The clinical trial involves the administration of **hydroxychloroquine sulfate** as the primary experimental medication. The product, marketed under the name PLAQUENIL 200 mg, is provided in the form of a **film-coated tablet**. The dosage is calculated based on the participant's body weight, with a recommended administration of 6 to 6.5 mg/kg/day. The route of administration is **oral**, and the maximum daily dose is capped at 600 mg. The treatment period extends up to 12 months. Compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the prescribed regimen.

In addition to the primary treatment, the trial utilizes an auxiliary medication, XYLOCAINE 10 mg/ml ADRENALINE 0.005 mg/ml, which is a **solution for injection**. This product contains the active substances **epinephrine bitartrate** and **lidocaine hydrochloride**. The solution is administered via **injection**, with a maximum daily dose of 100 mg. The treatment period for this auxiliary medication is limited to a single day. The use of this auxiliary treatment is intended to support the primary objective of the trial, which is to evaluate the effect of hydroxychloroquine on mast cell activation symptoms in patients with isolated cutaneous mastocytosis or indolent systemic mastocytosis with associated skin involvement.

Efficacy in this clinical trial will be assessed by evaluating the change in **mast cell activation symptoms** such as pruritus and flushes over a 12-month period. The primary endpoint is the change in these symptoms from the start of treatment to 12 months later. Secondary endpoints include the difference in mast cell mass and other symptoms like diarrhea, pollakiuria, arthralgia, and discomfort over the same period. Additionally, the safety of hydroxychloroquine treatment and the correlation between treatment effectiveness and serum hydroxychloroquine levels will be evaluated.