Neoplasms

Immune System Diseases

All Conditions

Skin and Connective Tissue Diseases

Symptoms and General Pathology

Rare Diseases

Mastocytosis

Urticaria

Mastocytosis, Cutaneous

Mastocytoma

Urticaria Pigmentosa

Skin Diseases

Skin Diseases, Vascular

Hypersensitivity

Hypersensitivity, Immediate

Neoplasms, Connective Tissue

Neoplasms, Connective and Soft Tissue

Neoplasms by Histologic Type

Mast Cell Activation Disorders

Skin Neoplasms

Pigmentation Disorders

Cutaneous Mastocytosis

This group will undergo skin biopsy, blood and buccal swab analyses

This group will undergo blood and buccal swab analyses

A skin biopsy will be obtained from a typical UP lesion in affected patients

skin biopsy

Blood will be obtained from subjects, parents and unaffected siblings

blood draw

Pediatric mastocytosis is an orphan disease, which encompasses several clinically distinct entities including solitary mastocytoma, urticaria pigmentosa, diffuse cutaneous mastocytosis and the newly recognized mast cell activation syndrome. The most common form of pediatric mastocytosis is cutaneous maculopapular mastocytosis (CMPM), also known as urticaria pigmentosa (UP). There are significant knowledge gaps regarding the genetic basis of pediatric mastocytosis and the functional activity of mast cells in this condition. The Pediatric Dermatology and Pediatric Oncology services at the University of Minnesota Masonic Children's Hospital are seeing significant growth in clinical volumes of pediatric mastocytosis, including rare, familial cases. The aims of this study are to prospectively explore germline risk for UP and to perform a mutational analysis to identify somatic mutations, beyond those currently identified, in pediatric patients with UP.

Urticaria pigmentosa (UP) is a relatively common disorder in pediatric patients, and little is known regarding the somatic and germline genetic variants associated with the disease. The University of Minnesota Masonic Children's Hospital is a regional referral center for pediatric patients with mast cell disorders. Collaborators on this study include several University departments including: Pediatric Dermatology, Pediatric Oncology, the Biomedical Genomics program, Lab Medicine and Pathology department. We hypothesize that because of differences observed in the clinical behavior of pediatric- and adult-onset mast cell disease, specifically UP, we will identify novel somatic gene variants in addition to c-KIT . We further hypothesize that we will observe novel germline genetic variants in pediatric UP distinct from what has previously been described in adults.

Specific Aims include the following:

Specific Aim 1: RNA Sequencing for Gene Expression and Mutation Analysis. Utilizing RNA sequencing (RNA-Seq), we will perform paired lesional and peripheral blood sequencing in UP cases to identify variation in gene expression and define novel somatic mutations associated with pediatric UP.

Specific Aim 2: Exploration of Germline Risk. Utilizing single nucleotide polymorphism (SNP) array, we will perform linkage analysis in UP cases and their unaffected family members to identify germline genetic variants associated with UP.

1. Discordant sibling analysis: Children with UP and their unaffected siblings will be compared to identify germline variants.
2. Identical twin and parent analysis: Identical infant twins with a severe UP phenotype will be compared with their unaffected parents.

Cutaneous Mastocytosis in Children: Analysis of Somatic and Germline Mutations

Fresh tissue from lesional skin will be obtained for gene expression and mutational analysis

SNP microarray analysis will be performed on DNA obtained from buccal swabs or whole blood samples. Samples from patients and unaffected family members will be compared.

University of Minnesota

Mastocytosis, Systemic

Systemic Mastocytosis

For each enrolled subject, 5 mL sample of peripheral blood and 1 mL sample of BM aspirate will be collected the same day to do diagnosis mastocytosis tests (quantification of the kit mutations by qPCR, plasma tryptase level, immunophenotyping of BM mastocytes by flow cytometry, BM tryptase level, degree of dilution of the BM aspirate...) using the WHO criteria as the reference standard.

Some samples will be extracted from bone marrow aspirate and peripheral blood on the inclusion day to do diagnosis tests. WHO criteria will be used as the reference standard.

Mastocytosis diagnosis

Cristina Livideanu, MD

The hypothesis of the study is that Bone Marrow Tryptase (MT) level is a diagnostic marker of Systemic Mastocytosis (SM). Determination of the bone marrow tryptase in Bone Marrow Aspirate (BMA) could be a new diagnostic criteria for systemic mastocytosis with sensitivity close to 100% and a low false negative rate. This new test could be useful to improve the ability to diagnose accurately systemic mastocytosis (in particular the indolent forms). Because of its limited invasiveness compared to bone marrow biopsy, it could also be considered as a test performed before bone marrow biopsy. Only patients with high bone marrow tryptase would then undergo bone marrow biopsy.

In the future and if validated by this study, bone marrow tryptase could be a useful marker of mast cell load and help to monitor the efficacy of treatment in systemic mastocytosis.

Mastocytosis are a group of disorders characterized by clonal accumulation of mast cells in various organs. Diagnosis of mastocytosis is challenging and patients remain undiagnosed for years. Using the diagnostic criteria defined by the World Health Organization (WHO) mastocytosis can be divided between Cutaneous Mastocytosis (CM) and Systemic Mastocytosis (SM).

Study suggested that measurement of tryptase in plasma from a Bone Marrow Aspirate (from BMA) could be useful for the diagnosis of SM. Results from a preliminary study at Toulouse University Hospital suggested that a Bone Marrow Tryptase Level (MT) of 50 µg/L or more may be a more sensitive diagnostic criterion (sensitivity of 94.7%) than the histological result of BMB (the major diagnostic criterion for SM with a sensitivity of 68 to 80% in expert centers) for diagnosis of SM in patients with mastocytosis in skin.

Because this preliminary study was done on a limited number of patients and in a single center, the diagnostic value of MT for the diagnosis of SM, has to be confirmed on a larger and more representative population.

In addition, the investigators propose to evaluate:

* The diagnostic accuracy of MT for diagnosis of SM in patients without mastocytosis in skin;
* The diagnostic accuracy of absolute and corrected MT for diagnosis of SM with and without mastocytosis in skin;
* The diagnostic accuracy of MT/ST ratio for diagnosis of SM with and without mastocytosis in skin;
* The diagnostic accuracy of flow cytometry performed on cells collected by BMA and maintained in a preservative solution for diagnosis of SM with and without mastocytosis in skin;
* The diagnostic accuracy of quantification of the fraction of KIT mutation-positive cells in peripheral blood for diagnosis of SM with and without mastocytosis in skin;
* Correlation the results of quantification of the fraction of KIT mutation-positive cells in peripheral blood with results of MT level, results of MT/ST ratio and results of absolute and corrected MT;
* Correlation the results of the CF performed both on the EDTA/TransFix® tubes and on sodium heparin tubes and validate the transport conditions (20-25°C within 24 to 96H) for the CF; these analyzes will be performed on the first 50 samples of BMA.

The samples for these diagnosis tests will be made on the day of inclusion. For each enrolled patient, one 5 mL sample of peripheral blood (EDTA) and 1 mL samples of BM aspirate (0,5 mL in a EDTA/TransFix® tube et 0,5 mL in a sodium heparinate tube) will be collected the same day, and shipped in less than 24 to 96H (+20-25°C) to a central laboratory.

For each patient, genomic DNA from total leucocytes will be purified from the peripheral blood EDTA samples, and used later for the quantification of the kit mutations by real-time qPCR. The plasma tryptase level will be measured from the peripheral blood EDTA sample after an aliquot has been taken for DNA extraction. The bone marrow aspirate sample will be used first for immunophenotyping of BM mastocytes by flow cytometry (FC), and then, after centrifugation, for measurement of BM tryptase level. The degree of dilution of the BM aspirate by peripheral blood will be estimated by comparing the percentage of CD16bright vs. CD16low granulocytes in BM samples, and used to adjust the BM tryptase. Tryptase measurements will be made from EDTA or Na, heparinate plasma, using a standardized fluoro enzyme immunoassay on an automated analyzer. Immunophenotyping of BM mastocytes will be performed on BM aspiration stabilized by TransFix® (a Cellular Antigen Stabilisation Reagent) (and for firsts 50 samples on BM aspiration in Na, heparinate) using a pre-defined mixture of anti-CD45/CD117/CD34/CD2/CD25/CD16 antibodies, coupled to appropriate fluorochromes. Genomic DNA from BM leucocytes will be extracted from 300-500µL of peripheral blood (both anti coagulated with EDTA) using a Promega DNA automated extractor, and subsequently stored at +4°C. Quantitative PCR will be performed using a pre-validated qPCR assay (Life Technologies, Foster City, CA) with a 7900HT Fast Real-Time PCR System (Life Technologies).

The end of study visit is performed the same day that the patient is seen to be made aware of the results of the clinical and laboratory investigations made. This is also the day when the planned medical management of mastocytosis is discussed.

Diagnostic Value of Bone Marrow Tryptase in Systemic Mastocytosis

Evaluation of the Diagnostic Value of Level of Bone Marrow Tryptase in Adult Systemic Mastocytosis

Aliquot of the bone marrow aspirate sample will be used after centrifugation for measurements of bone marrow tryptase level.

The degree of dilution of the bonne marrow aspirate by peripheral blood will be estimated by comparing the percentage of CD16bright vs CD16low granulocytes in bone marrow samples and used to adjust the bone marrow tryptase.

Immunophenotyping of bone marrow mastocytes will be performed on bone marrow aspiration stabilized by Transfix using a pre-defined mixture of anti-CD45/CD117/CD34/CD2/CD25/CD16 antibodies.

Genomic DNA from total leucocytes will be purified from the peripheral blood samples and used for the quantification of the kit mutation by qPCR

University Hospital, Toulouse

TF 002

Marcus Maurer, Prof

The current study will investigate the effects of TF002 on cutaneous mastocytosis or cutaneous involvement of systemic mastocytosis as compared to clobetasol proprionate (positive control) and a general skin care product without active ingredient targeting mastocytosis (negative control) based on clinical effects on Darier´s signs and the histological evaluation of mast cell numbers in skin bioptic material.

This is a randomised, double-blind, placebo- and active-controlled study with intra-individual comparison of test areas.

The primary study target is to evaluate the safety and efficacy of TF002 for the treatment of cutaneous mastocytosis or systemic mastocytosis with skin involvment. The treatment period of 14 days was adjusted to the maximum recommended treatment period for the comparator Dermoxinale®.

Since there are no approved therapies for this indication a placebo controlled design was chosen.

There are some reports about transient treatment effects using high potent steroids like clobetasol in mastocytosis. This triggered the decision to use Dermoxinale® as positive control.

To validate the clinical scores used in the study, surrogate markers describing the Darier´s sign (thermography, volumetric test) will be evaluated optionally.

Efficacy and Safety of TF002 in Cutaneous Mastocytosis

JADO Technologies GmbH

Blood and Lymph Conditions

Behaviors and Mental Disorders

Heart and Blood Diseases

Leukemia

Aggression

Telangiectasis

Leukemia, Mast-Cell

Anthony L Boral, MD, PhD

The Mast Cell Connect Registry is a voluntary, observational database that will capture demographic, socioeconomic, and disease information directly from patients with mastocytosis via a secure web-based tool. No experimental intervention is involved.

Mastocytosis is an extremely rare and heterogeneous spectrum of diseases characterized by the buildup of genetically altered mast cells. Patients experience a wide range of symptoms and in some cases, mast cell buildup can lead to organ dysfunction and failure. Current treatments address disease symptoms and not the underlying cause. To facilitate the development of new therapies for mastocytosis, it is important for the community to support clinical trials and to document the impact of the disease, including disease natural history and the impact on patients, in a systematic way. Mast Cell Connect is a web-based registry that allows mastocytosis patients and caregivers to enter information about the experience of the patient living with mastocytosis directly into an online data collection tool.

The Mast Cell Connect Registry allows mastocytosis patients and caregivers to enter information about the experience of the patient living with mastocytosis directly into a web-based data collection tool. Two forms of data will be collected: responses to surveys administered on the web-based portal, and de-identified data curated from medical reports uploaded by patients or their caregivers.

Mast Cell Connect: A Registry for Patients With Mastocytosis

PatientCrossroads

Blueprint Medicines Corporation

Quality of Life

The comprehension test will be done through structured interviews in which the principal investigator will ask if the patient has had difficulty understanding the recommendations and questions, will check the interpretation of all items and the understanding of each word by the patient. In case of problems, the investigator will propose and / or test translation alternatives, or will ask the patient to propose alternatives.

A structured interview with every patient

Cristina Bulai Livideanu, MD

Mastocytosis is a heterogeneous rare disease. A 27-item questionnaire to assess the quality of life of patients with cutaneous/ indolent systemic mastocytosis was developed in the German language and validated in the English language in 2015.

The team of the University Charité Berlin and the company Moxie - intellectual proprietor of the questionnaire - proposed the use of the recommendations of Baiardini et al. 2010, for linguistic adaptation of this questionnaire in other languages.

The first two steps of the program of linguistic translation have already been carried out under the direction and supervision of teams from Charité University, Berlin and Moxie Company. The result of these two steps is a secondary version of the Mc-QoL questionnaire in French. The last step of this adaptation process in the target language (French, France) needs to be carried out and it is the subject of this study.

The objective of this study is the French language adaptation of the Mc-QoL questionnaire in adult patients with indolent cutaneous and / or indolent systemic mastocytosis.

During this study, the second version of the Mc-QoL questionnaire in French will be evaluated on 10 adult patients, with cutaneous and / or indolent systemic mastocytosis and native in the French language. The comprehension tests will be carried out by means of the structured interviews during which the investigator will ask if the patient has had difficulties to understand the recommendations, the questionnaires, will verify the interpretation of all the items and the understanding of each word by the patient. In case of problems, the investigator will propose and / or test translation alternatives, or will ask the patient to propose alternatives.

Revisions to the second version of the Mc-QoL questionnaire in French will be done to rectify the problems identified in the conceptual equivalence. The result will be a third French version of the Mc-QoL questionnaire, which will be the final version.

A report on the interviews will be written in English: it will describe the number of respondents, their age, the time required to complete the questionnaire, the difficulties encountered, the solutions suggested and retained and how the third version of the questionnaire was produced.

Adaptation of the Questionnaire "Regarding Patient's Quality of Life With Mastocytosis" in the French Language

The understanding of aspects of the questionnaire Mc-QoL (version "secondary" in French) will be evaluated for each patient:

- the instructions

The understanding of aspects of the questionnaire Mc-QoL (version "secondary" in French) will be evaluated for each patient :

- the questions (items) and the proposed answers

The understanding of aspects of the questionnaire Mc-QoL (version "secondary" in French) will be evaluated for each patient :

- the layout of the questionnaire

The understanding of aspects of the questionnaire Mc-QoL (version "secondary" in French) will be evaluated for each patient :

- the language (words) used, if it is simple and appropriate

one to two session of pigment laser (532 nm)

Pigment laser

Christina BULAI LIVIDEANU, MD

Cristina BULAI LIVIDEANU, MD

Cutaneous mastocytosis can be isolated or associated with systemic involvement. Urticaria pigmentosa affects around 80 to 85% of adult patients with cutaneous mastocytosis. It is also frequently present in patients with mastocytosis associated with systemic involvement (80% of patients in our experience).

This skin damage is one of the causes of deterioration in quality of life in patients with mastocytosis, through the loss of self-esteem, due to the appearance of lesions. However there are not treatment for urticaria pigmentosa.

Skin involvement in mastocytosis is linked to the accumulation of abnormal mast cells in the dermis. However, the mast cells are not pigmented and the brown-brown color characteristic of Urticaria pigmentosa is explained by melanin pigmentation of the epidermal basal layer.

Cutaneous mastocytosis can be isolated or associated with systemic involvement. Urticaria pigmentosa affects around 80 to 85% of adult patients with cutaneous mastocytosis. It is also very frequently present in patients with mastocytosis associated with systemic involvement (80% of patients in our experience).

This skin damage is one of the causes of deterioration in quality of life in patients with mastocytosis, through the loss of self-esteem, due to the appearance of lesions. However ,there is not a treatment for urticaria pigmentosa.

Skin involvement in mastocytosis is linked to the accumulation of abnormal mast cells in the dermis. However, the mast cells are not pigmented and the brown-brown color characteristic of pigmentary urticaria is explained by melanin pigmentation of the epidermal basal layer. This characteristic is often described on skin biopsies of pigmentary urticaria analyzed in hematoxilin-eosin.

The 532 nm Q-Switched laser is known to improve lesions characterized by the presence of melanin pigment in the basal layer of the epidermis, with very little risks. This later is explained by the reduced penetration of light at 532 nm into the skin and the emission time of the laser light which is very low (of the order of a few nanoseconds) for Q-Switched lasers. In the literature, 2 case reports report an efficiency of the laser at 532 nm in this indication in adults.

The hypothesis of this study is that 2 sessions of Q-switched laser could improve the skin lesions of urticaria pigmentosa, leading to an improvement in self-esteem.

Improvement of Pigmented Skin Lesions in Patients With Mastocytosis After Performing 2 Sessions of Pigment Laser

Evaluation of the Improvement of Pigmented Skin Lesions in Patients With Mastocytosis After Performing 2 Sessions of Pigment Laser : Pilot Study Conducted at a Reference Centre Mastocytoses (LaserMasto)

Global clinical evolution with IGA " Improvement Global Assessment" (scale with 5 points : no improvement or aggravation/minimal improvement/moderate improvement/significant improvement/complete disappearance) by blind evaluator in month 4 versus baseline

Global clinical evolution with IGA " Improvement Global Assessment" (scale with 5 points : no improvement or aggravation/minimal improvement/moderate improvement/significant improvement/complete disappearance) by blind evaluator in month 1 versus baseline

Global clinical evolution with IGA " Improvement Global Assessment" (scale with 5 points : no improvement or aggravation/minimal improvement/moderate improvement/significant improvement/complete disappearance) by blind evaluator in month 9 versus baseline

Global clinical evolution with IGA " Improvement Global Assessment" (scale with 5 points : no improvement or aggravation/minimal improvement/moderate improvement/significant improvement/complete disappearance) by the principal investigator in month 4 versus baseline

Global clinical evolution with IGA " Improvement Global Assessment" (scale with 5 points : no improvement or aggravation/minimal improvement/moderate improvement/significant improvement/complete disappearance) by the principal investigator in month 1 versus baseline

Global clinical evolution with IGA " Improvement Global Assessment" (scale with 5 points : no improvement or aggravation/minimal improvement/moderate improvement/significant improvement/complete disappearance) by the principal investigator in month 9 versus baseline

the surface area of the target pigment skin lesion (mm2) versus baseline

qualitative analysis of the patient verbatim after an interview

Global clinical evolution with IGA " Improvement Global Assessment" (scale with 5 points : no improvement or aggravation/minimal improvement/moderate improvement/significant improvement/complete disappearance) by patient versus baseline

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Cutaneous Mastocytosis in Children: Analysis of Somatic and Germline Mutations	NCT02761473	Urticaria Pigme... Cutaneous Masto...	skin biopsy blood draw	3 Months - 23 Years	University of Minnesota
Diagnostic Value of Bone Marrow Tryptase in Systemic Mastocytosis	NCT02441166	Systemic Mastoc...	Mastocytosis di...	18 Years -	University Hospital, Toulouse
Cutaneous Mastocytosis in Children: Analysis of Somatic and Germline Mutations	NCT02761473	Urticaria Pigme... Cutaneous Masto...	skin biopsy blood draw	3 Months - 23 Years	University of Minnesota
Efficacy and Safety of TF002 in Cutaneous Mastocytosis	NCT00457288	Cutaneous Masto...	TF 002	18 Years -	JADO Technologies GmbH
Mast Cell Connect: A Registry for Patients With Mastocytosis	NCT02620254	Mastocytosis		-	Blueprint Medicines Corporation
Adaptation of the Questionnaire "Regarding Patient's Quality of Life With Mastocytosis" in the French Language	NCT03632811	Cutaneous Masto... Indolent System...	A structured in...	18 Years -	University Hospital, Toulouse
Mast Cell Connect: A Registry for Patients With Mastocytosis	NCT02620254	Mastocytosis		-	Blueprint Medicines Corporation
Improvement of Pigmented Skin Lesions in Patients With Mastocytosis After Performing 2 Sessions of Pigment Laser	NCT04377828	Cutaneous Masto...	Pigment laser	18 Years -	University Hospital, Toulouse

Spots Global Cancer Trial Database for cutaneous mastocytosis