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

Sheila Galbraith, MD

The purpose of this study is to determine how long the skin lesions usually last and what kind of symptoms and signs children with urticaria pigmentosa may develop over the years. This information will allow physicians to better care for patients who have been diagnosed with this disease and to provide their parents with more complete information regarding what to expect for the future of their child. This research is being done because many unanswered questions remain regarding children with urticaria pigmentosa and its course.

This study involves children, of age 0-18 years old who are diagnosed with urticaria pigmentosa during their visit at the Pediatric Dermatology Clinic. Parents and child will be interviewed to gain medical and family history, in addition, the doctor will perform a physical exam and take a photograph. Children older than 4 years of age will complete the "Children Dermatology Life Quality Index." Children less than 4 years of age with an active disease will have laboratory tests requiring a sample of blood (1 teaspoon).

Patients will receive $50 for their first office visit as financial reimbursement for participating in the study.

Natural History of Urticaria Pigmentosa in Children

Society for Pediatric Dermatology

Medical College of Wisconsin

Syndrome

Mast Cell Activation Syndrome

Participants affected by cutaneous and systemic mastocytosis with or without eye disabilities

Eye examination :

Ocular tonometry to determine intraocular pressure Refraction assessment Retina examination Slit lamp examination Visual acuity Schirmer's test Corneal topography Funduscopic examination Optical coherence tomography

Ophthalmological examination

Mastocytosis is a rare condition characterized by an accumulation of mast cell cells in one or more organs such as the liver, bone marrow, spleen and intestines. Its prevalence in the general population is 1 in 10,000.

This pathology is due to the proliferation of a mast cell clone and the excessive release of inflammatory mediators which lead to abnormal tissue infiltration.

To date, there are only a few cases reporting ocular and orbital manifestations of mastocytosis.

Our prospective, interventional and single-center study consist in describing the ocular functional manifestations and ocular surface abnormalities of patients with systemic and cutaneous mastocytosis.

Patient with systemic or cutaneous mastocytosis will be included in the study. Data about organ involvement of mastocytosis will be collected. Participants will be screened with a medical and eye disease history. They will also have an eye exam.

Participants will provide a tears sample.

Ocular and Palpebral Manifestations of Mastocytosis (MOOMA)

Number of patients with functional complaints or abnormalities of the surface, orbit, anterior and posterior segment of the eyeball.

Details of functional complaints, abnormalities of various specialized examinations such as ocular tonometry to determine intraocular pressure, Refraction assessment, Retina examination, Slit lamp examination, Visual acuity, Schirmer's test, Corneal topography, Funduscopic examination, Optical coherence tomography

Significative association with a mastocytosis subtype or certain organ involvements or biological abnormalities

Poitiers University Hospital

Melody C Carter, M.D.

This study will evaluate children with mastocytosis, a disease of excessive mast cells in tissues such as skin and bone marrow, to identify the cause of the disease and describe its course. Mast cells can release chemicals that cause itching, blisters, flushing, bone pain, and abdominal pain. Usually, mastocytosis in children involves the skin only and is of limited duration. This study, however, will focus on children with more severe disease that more closely resembles adult-onset mastocytosis.

Patients up to 21 years of age with childhood-onset mastocytosis may be eligible for this study. Candidates must have one or more of the following abnormalities, which indicate severe disease: enlarged liver or spleen; diffuse skin involvement; history of gastrointestinal bleeding or peptic ulcer; bone marrow biopsy with abnormal mast cells either in number or shape; elevated blood levels of the enzyme tryptase; or abnormal hemoglobin, white blood cells, platelets, or clotting factors.

Participants will have a medical history and physical examination; various blood tests, including studies to identify genetic changes that are important in the growth, development, and functioning of human mast cells; and bone marrow aspiration and biopsy. For the bone marrow procedure, the skin over the hipbone and the outer surface of the bone itself are numbed with an injection of local anesthesia. Then, a special needle is inserted into the hipbone and about 2 tablespoons of bone marrow are drawn into a syringe. Another needle is then inserted through the first needle to collect a small piece of the bone marrow. Pain will be managed according to the individual patient s needs. Additional procedures, such as a gastroenterology consultation, colonoscopy to examine the colon, or computerized axial tomography (CT) or ultrasound of the abdomen to assess the liver and spleen, may be done if medically indicated. Standard medical treatment, including antihistamines for itching or steroids for abdominal cramping or diarrhea, will be recommended as appropriate.

Patients biologic parents may also be enrolled to provide a blood sample for genetic analysis and a bone marrow aspirate and biopsy for clinical and research purposes.

Patients will return to NIH once a year for follow-up evaluations until their disease is stable or until the 5-year study ends.

...

Mastocytosis in infants and children is an unusual disease characterized by an excess of mast cells in tissues. In pediatric onset mastocytosis, disease is usually localized to the skin and disease is considered to be of limited duration. However, a subset of children appear to develop a clinical picture resembling that observed in adults who have adult-onset disease. This study will focus on children with more severe mastocytosis in an attempt to define its pathogenesis, focusing on mutations and polymorphisms in genes regulating mast cell proliferation and survival to determine if they might contribute to this disease pattern. If severe pediatric-onset disease does not fit within the existing classification, new criteria of diagnosis must be proposed for the pediatric age group.

This study will examine children and young adults age birth to 21 years with pediatric-onset disease previously enrolled on NIAID mastocytosis protocols, or as a result of physician referral, which have disease more consistent with adult-onset disease or parameters associated with increased morbidity. The evaluation may include serum tryptase, blood count, bone marrow biopsy and aspirate, morphology and mutational analysis. Subjects may be asked to return in 12-24 months for assessment. If relevant mutation effecting mast cell growth and function are identified, such mutations will be sought in the biologic parents as appropriate, but only when such mutations are believed to be germ line (not somatic) mutations. This study will aid in the understanding of the characteristics of severe mastocytosis in the pediatric age group.

Cause and Natural Course of Pediatric-Onset Mastocytosis

Determining the Pathogenesis of Systemic Pediatric-Onset Mastocytosis

National Institute of Allergy and Infectious Diseases (NIAID)

Blood and Lymph Conditions

Behaviors and Mental Disorders

Heart and Blood Diseases

Leukemia

Aggression

Telangiectasis

Mastocytosis, Systemic

Leukemia, Mast-Cell

Systemic Mastocytosis

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

Nervous System Diseases

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Preleukemia

Leukemia, Myelomonocytic, Chronic

Leukemia, Myelomonocytic, Juvenile

Myelodysplastic Syndromes

Hematologic Neoplasms

Myeloproliferative Disorders

Soft Tissue Neoplasms

Hematologic Diseases

Immune Complex Diseases

Dementia

Aberrant Motor Behavior in Dementia

Behavioral Symptoms

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Non Lymphoblastic Leukemia

Chronic Myelomonocytic Leukemia

Juvenile Myelomonocytic Leukemia

Chronic Graft Versus Host Disease

Acute Graft Versus Host Disease

Chronic Myeloproliferative Disorders

All Drugs and Chemicals

Antigen-Antibody Complex

Bezuclastinib is administered as tablets to be taken orally, continuously in 28-day cycles.

bezuclastinib

Hina Jolin, PharmD

Rachael Easton, MD, Ph.D.

This is an open-label, two-part Phase 2 study investigating CGT9486 for the treatment of patients with Advanced Systemic Mastocytosis (AdvSM), including patients with Aggressive SM (ASM), SM with Associated Hematologic Neoplasm (SM-AHN), and Mast Cell Leukemia (MCL).

There are two parts to this study, including Part I, Dose Optimization, and Part II Expansion. Part II is separated into two stages.

(Apex) Bezuclastinib in Patients With Advanced Systemic Mastocytosis

A Phase 2 Open-Label, Multicenter Clinical Study of the Safety, Efficacy, Pharmacokinetic, and Pharmacodynamic Profiles of CGT9486 as a Single Agent in Patients With Advanced Systemic Mastocytosis

Incidence of AEs according to CTCAE version 5.0 or higher

Percentage change in plasma concentrations of bezuclastinib

Percentage change in mast cell infiltration in the bone marrow and percentage change in eosinophilia and monocytosis in the blood

0 -10 points (higher values represent worse symptom outcomes)

0 - 7 points (higher values represent better symptom outcomes)

0 - 100 (higher values represent better symptom outcomes)

0 - 252 (higher values represent worse symptom outcomes)

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
Natural History of Urticaria Pigmentosa in Children	NCT00467792	Urticaria Pigme...		- 18 Years	Medical College of Wisconsin
Ocular and Palpebral Manifestations of Mastocytosis (MOOMA)	NCT04978740	Mast Cell Activ... Mast Cell Activ... Mast Cell Disea... Urticaria Pigme...	Ophthalmologica...	18 Years -	Poitiers University Hospital
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
Ocular and Palpebral Manifestations of Mastocytosis (MOOMA)	NCT04978740	Mast Cell Activ... Mast Cell Activ... Mast Cell Disea... Urticaria Pigme...	Ophthalmologica...	18 Years -	Poitiers University Hospital
Natural History of Urticaria Pigmentosa in Children	NCT00467792	Urticaria Pigme...		- 18 Years	Medical College of Wisconsin
Cause and Natural Course of Pediatric-Onset Mastocytosis	NCT00050193	Mastocytosis		- 21 Years	National Institutes of Health Clinical Center (CC)
Mast Cell Connect: A Registry for Patients With Mastocytosis	NCT02620254	Mastocytosis		-	Blueprint Medicines Corporation
Mast Cell Connect: A Registry for Patients With Mastocytosis	NCT02620254	Mastocytosis		-	Blueprint Medicines Corporation
Cause and Natural Course of Pediatric-Onset Mastocytosis	NCT00050193	Mastocytosis		- 21 Years	National Institutes of Health Clinical Center (CC)
(Apex) Bezuclastinib in Patients With Advanced Systemic Mastocytosis	NCT04996875	Advanced System... SM With an Asso... Mast Cell Leuke... Aggressive Syst...	bezuclastinib	18 Years -	Cogent Biosciences, Inc.

Spots Global Cancer Trial Database for urticaria pigmentosa