Skin and Connective Tissue Diseases

All Conditions

Symptoms and General Pathology

Respiratory Tract (Lung and Bronchial) Diseases

Immune System Diseases

Neoplasms

Rare Diseases

Eczema

Syndrome

Asthma

Mastocytosis

Hypersensitivity

Anaphylaxis

Urticaria

Food Hypersensitivity

Mast Cell Activation Syndrome

Chronic Urticaria

Skin Diseases

Skin Diseases, Vascular

Hypersensitivity, Immediate

Neoplasms, Connective Tissue

Neoplasms, Connective and Soft Tissue

Neoplasms by Histologic Type

Mast Cell Activation Disorders

Chronic Disease

Disease Attributes

Chronic Graft Versus Host Disease

Tak H Lee

Activation of mast cells in the immune system is known to cause allergic reactions sometimes with severe systemic symptoms. The investigators have recently developed a blood-based mast cell activation diagnostic test in which levels of functional activation in-vitro in primary cultured mast cells generated from the peripheral blood of single individuals can be assessed. It is the hypothesis that the test can be used to predict the potential state of in-vivo mast cell activation in any individual based on the functional activation profiles exhibited by their cultured mast cells. The investigators now wish to translate their in-vitro findings in a pilot study to disease groups where mast cell activation is expected to be high. These include highly allergic individuals; those with chronic idiopathic urticaria; those with mastocytosis; and those with the mast cell activation syndrome. Furthermore, they will use the functional genomics approach to identify gene expression biomarkers that are correlated with such diseases. The results will be compared with data that have been collected from a cohort of healthy control blood donors.

The objective of this study is to assess whether patients with severe allergic diseases exhibit high levels of mast cell activation as determined by the mast cell activation diagnostic test the investigators have developed. They anticipate that patients with history of severe allergic reactions will show up as high responders in the blood-based mast cell activation diagnostic test. Moreover, using microarray analysis as the approach for gene expression studies, they anticipate further that genomics biomarkers that are correlated with the high functional activation of the in-vitro mast cells derived from these patients can be readily identified.

About 100 ml of peripheral venous blood from individual patients will be drawn into heparinized syringes and collected in a blood-collecting bag/tube containing silica. The bag/tube will be promptly processed for the generation of primary human mast cell cultures using the protocol that has previously been developed \[Inflammation Research 66: 25 (2017). After culturing for 9 weeks, the resulting human mast cells will be analyzed for both their functional activity in terms of histamine release in response to the activation of high-affinity Immunoglobulin E (IgE) receptors in these cells and their gene expression profiles using microarray analysis. The in-vitro functional and genomics data will be correlated with specific diagnoses and measurements of blood prostaglandin D2 (PGD2), PGD2 metabolites, tryptase and histamine levels in blood. For mediator assays, plasma from each subject will be collected after the cluster of differentiation 34 positive (CD34+) isolation step and the samples will be aliquoted and frozen at -80 degrees centigrade for subsequent analysis.

Mast Cell Activation Test in Allergic Disease

Assessment of Mast Cell Activation Diagnostic Test in Patients With Allergic Disease

Mast Cell Activation Test results of high/low level of house dust mite sensitivity by using normal donor cultured mast cells for validation.

Patient's serum was incubated with mast cells derived from normal donors for detection of mast cell activation as evidenced by histamine release.

percentage of total histamine release by normal average responder mast cells that had been activated with patient's serum

percentage of total histamine release by patient's mast cells that had been activated with anti-IgE

Percentage of total histamine release when patient's mast cells were activated with patient's own serum and Der p2. Each patient's results are reported individually.

Cell yield of patient's mast cell culture after 9 weeks in culture as an index of cell growth and differentiation.

Chinese University of Hong Kong

Stanford University

Hong Kong Sanatorium & Hospital

Director Allergy Centre

Mast cell activation test employing normal donor cultured mast cells and allergic patient serum samples

Validation Group

Male patient, Total IgE: 28918KU/L; Der p2IgE: 64.4KU/L; clinical diagnosis: Eczema

SH#1

Male patient, Total IgE: 22311KU/L; Der p2IgE: 91.24KU/L; clinical diagnosis: Eczema

SH#2

Female patient, Total IgE: 5333KU/L; Der p2IgE: \>100KU/L; clinical diagnosis: Eczema

SH#3

Male patient, Total IgE: 4070KU/L; Der p2IgE: \>100KU/L; clinical diagnosis: Eczema, Urticaria

SH#4

Male patient, Total IgE: 379KU/L; Der p2IgE: 0.15KU/L; clinical diagnosis: Exercise-induced anaphylaxis

SH#5

Female patient, Total IgE: 13KU/L; Der p2IgE: \<0.1KU/L; clinical diagnosis: Mast cell activation syndrome

SH#6

Male patient, Total IgE: 67KU/L; Der p2IgE: None KU/L; clinical diagnosis: Urticaria

SH#7

Total

Age, Categorical

Sex: Female, Male

Race (NIH/OMB)

Hong Kong

Region of Enrollment

Clinical diagnosis of participants before Mast cell activation test

Clinical diagnosis

During recruitment period, no participants with asthma, food allergy, mastocytosis were recruited.

Prof. Tak Hong Lee

High level of house dust mite sensitivity

Low level of house dust mite sensitivity

Mast cells were cultured from blood of normal donors to validate the (Mast Cell Activation) MAT assay. The serum samples were obtained from allergic patients with sensitivities to Der p2 and used for passive sensitization of normal donor mast cells followed by their activation by Der p2 allergen. Data were collected only from the validation group.

Mast Cell Activation Test Results for Validation Group

Male patient, Total IgE: 28918 KU/L; Der p2 IgE: 64.4 KU/L; clinical diagnosis: Eczema

Male patient, Total IgE: 22311 KU/L; Der p2 IgE: 91.24 KU/L; clinical diagnosis: Eczema

Female patient, Total IgE: 5333 KU/L; Der p2 IgE: \>100 KU/L; clinical diagnosis: Eczema

Male patient, Total IgE: 4070 KU/L; Der p2 IgE: \>100 KU/L; clinical diagnosis: Eczema, Urticaria

Male patient, Total IgE: 379 KU/L; Der p2 IgE: 0.15 KU/L; clinical diagnosis: Exercise-induced anaphylaxis

Female patient, Total IgE: 13 KU/L; Der p2 IgE: \<0.1 KU/L; clinical diagnosis: Mast cell activation syndrome

Male patient, Total IgE: 67 KU/L; Der p2 IgE: None KiloUnits (KU)/L; clinical diagnosis: Urticaria

Serum samples were obtained from 19 patients in total, of whom 12 were in the validation group. The other 7 patients were studied more extensively in the trial and their data is reported individually in this section and thereafter.

Evaluation of Patient's Serum for Autoreactivity on Normal Average Responder Mast Cell Activation

Mast cells derived from the validation group is reported as a group (mean +/-SD). The other 7 allergic patients were analysed and reported individually as explained earlier.

Percentage Histamine Release by Normal Average Responder Mast Cells + Patient's Serum to Assess Autoreactivity

Mast cells derived from 7 allergic patients were analysed and reported individually. Patients in the validation group were not measured for this outcome and their samples were only used to validate the assay.

Percentage Histamine Release by Patient's Mast Cells + Immunoglobulin E (IgE)/Anti-IgE

Percentage of Histamine Release by Patient's Mast Cells + Patient's Serum + Allergen

Cell Yield Per 100ml Blood

Overall Study

Mastocytosis, Systemic

Systemic Mastocytosis

Antineoplastic Agents

All Drugs and Chemicals

Amino Acids

Imatinib Mesylate

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

Imatinib mesylate 300 or 400 mg daily for 12 months.

* In patients without B or C findings and without biological progression: 300 mg/24 h p.o during one year or until progression/unacceptable toxicity.
* In patients with B or C findings or biological progression: 300 mg/24 h p.o for two weeks and then 400 mg/24 h p.o for a total of one year of therapy, or until progression/unacceptable toxicity.

Luis Escribano, MD, PhD

The aim of this study is to evaluate the efficacy in terms of clinical and biological response rates of Imatinib Mesylate therapy in patients with systemic mastocytosis lacking KIT mutations.

In vitro studies have proven that imatinib inhibits wild type Kit (wtKit) and suppresses proliferation of the HMC-1V560G cell line, while it is ineffective on inhibiting the growth of HMC-1V560G, D816V cells. Apart from wtKit, Kit molecules carrying mutations in the extracellular, transmembrane and juxtamembrane domains, such as V560G, F522C and K509I, remain sensitive to imatinib. In contrast, several experiments have provided compelling evidence regarding the resistance against the growth-inhibitory effects of imatinib on cells carrying the D816V KIT mutation. As a consequence, sensitive and specific methods should be used in order to avoid "false" KIT mutation-negative cases and, for that purpose, mainly in cases with low bone marrow mast cell numbers, mutational studies should be performed using highly purified bone marrow mast cells by means of Facs sorting systems better than whole bone marrow, unsorted mononuclear cell fraction or mononuclear cell fraction pre-enriched using magnetic beads conjugated with anti-CD25 monoclonal antibody. In the present study mutational studies were performed in all cases in purified bone marrow mast cells (purity \> 97%) using a FACSaria system (Becton-Dickinson Biosciences) as previously described.

Patients without B or C findings according to the World Health Organization, and without features of biological progression of the disease receive oral Imatinib Mesylate 300 mg daily for up to 12 months or until clinical progression/unacceptable toxicity. Patients with B or C findings or biological progression initially receive oral Imatinib Mesylate 300 mg daily for two weeks; then, dose is increased up to 400 mg/day except in patients who develop hematological or any other dose-limiting toxicity.

Biological progression is defined as the presence of at least one of the following features: i) increased serum tryptase levels \> 200 ng/mL, ii) diffuse bone sclerosis, iii) patchy sclerosis with osteolysis and increased risk of bone fracture or significant bone pain, and, iv) organomegalies or lymph node enlargement due to mastocytosis.

Imatinib in KIT-negative Systemic Mastocytosis

Imatinib Mesylate Therapy in Systemic Mastocytosis Patients Lacking KIT Mutations

The grade of bone marrow infiltration is evaluated before and after 6 months of therapy by bone marrow histology and cytology, and flow cytometry performed on highly-purified bone marrow mast cells from patients with B or C findings

The grade of bone marrow infiltration is evaluated before and after 6 months of therapy by bone marrow histology and cytology, and flow cytometry performed on highly-purified bone marrow mast cells from patients without B or C findings, and from those with B or C findings who show response at the intermediate check-point (after 6 months of therapy)

Skin lesions are evaluated before and after therapy by macroscopic examination and skin biopsy.

Clinical symptoms such as pruritus, flushing, gastrointestinal symptoms and anaphylaxis are assessed before and after therapy using a clinical questionnaire that includes the type, frequency and severity of each symptom.

Organomegalies and adenomegalies are assessed before and after therapy by abdominal ultrasound.

Bone alterations are assessed before and after therapy by X-ray survey.

Genetic abnormalities are assessed before and after therapy by sequencyng analysis of the c-kit gene and the HUMARA assay.

Serum tryptase is measured before and after therapy.

The psychological impact of the disease and the quality of life of patients are evaluated before and after therapy by the Dermatology Life Quality Index.

Hospital Virgen de la Salud

Director Instituto de Estudios de Mastocitosis de Castilla La Mancha

Pruritus

Flushing

Psychotropic Drugs

Respiratory System Agents

Anti-Allergic Agents

Anti-Inflammatory Agents

Histamine Antagonists

Histamine H1 Antagonists

Antidepressive Agents

Leukotriene Antagonists

Proton Pump Inhibitors

Cromolyn Sodium

Experimental Arm:

Masitinib (titration to 6.0 mg/kg/day) administered as an add-on to optimal concomitant symptomatic treatment (i.e. best supportive care, BSC).

Participants receive masitinib (3.0 mg/kg/day), given orally twice daily, with a dose escalation to 4.5 mg/kg/day after 4 weeks of treatment, followed by dose escalation to 6.0 mg/kg/day after 4 weeks of treatment. Each ascending dose titration is subjected to a safety control.

Placebo Comparator:

Matching placebo administered as an add-on to optimal concomitant symptomatic treatment (i.e. best supportive care, BSC)

Masitinib

Placebo

Optimal concomitant symptomatic treatments. Includes: H1- and H2-antihistamines, proton pump inhibitors (PPI), sodium cromoglycate, antidepressants, leukotriene antagonists and corticosteroids.

Best Supportive Care

Clinical Study Coordinator

Cristina Bulai Livideanu, MD, MSc

The purpose of this study is to evaluate the efficacy and safety of oral masitinib versus placebo in the treatment of patients suffering from smouldering or indolent systemic mastocytosis with severe symptoms of mast cell mediator release, unresponsive to optimal symptomatic treatment.

Masitinib is a selective tyrosine kinase inhibitor that modulates mast cell activity via inhibition of c-Kit, Lyn and Fyn kinase signaling pathways. This is a multicenter, randomized, double-blind, placebo-controlled, 2-parallel-group, trial comparing oral masitinib versus placebo in the treatment of patients suffering from smouldering or indolent systemic mastocytosis with severe symptoms of mast cell mediator release (also referred to as handicaps), unresponsive to optimal symptomatic treatment. The treatment period is 24 weeks. Participants receive masitinib (3.0 mg/kg/day), given orally twice daily, with a dose escalation to 4.5 mg/kg/day after 4 weeks of treatment, followed by dose escalation to 6.0 mg/kg/day after 4 weeks of treatment. Each ascending dose titration is subjected to a safety control.

Masitinib in Severe Indolent or Smoldering Systemic Mastocytosis Unresponsive to Optimal Symptomatic Treatment

Phase 3 Study to Compare Oral Masitinib to Placebo in Treatment of Patients With Smouldering or Indolent Severe Systemic Mastocytosis, Unresponsive to Optimal Symptomatic Treatment

Cumulative response in at least one of three severe baseline symptoms of mast cell mediator release (pruritus, flushes, or depression). Response was defined as a 75% improvement from baseline for any of these three symptoms. Cumulative response was defined as the number of actual responses between weeks 8 and 24, divided by the total number of possible responses over the same treatment period (ie, with five scheduled visits, each patient had a maximum of five to 15 possible responses depending on the number of severe baseline symptoms).

Cumulative response in at least one of four severe baseline symptoms of mast cell mediator release (pruritus, flushes, depression, or asthenia). Response is defined as a 75% improvement from baseline for any of these four symptoms. Cumulative response was defined as the number of actual responses between weeks 8 and 24, divided by the total number of possible responses over the same treatment period (ie, with five scheduled visits, each patient had a maximum of five to 20 possible responses depending on the number of severe baseline symptoms).

Cumulative response in at least one of two severe baseline symptoms of mast cell mediator release (pruritus or flushes). Response is defined as a 75% improvement from baseline for either of these two symptoms. Cumulative response is defined as the number of actual responses between weeks 8 and 24, divided by the total number of possible responses over the same treatment period (ie, with five scheduled visits, each patient had a maximum of five to 10 possible responses depending on the number of severe baseline symptoms).

Cumulative response on each of the individual handicaps. Response is defined as a 75% improvement from baseline for either of these two symptoms. Cumulative response is defined as the number of actual responses between weeks 8 and 24, divided by the total number of possible responses over the same treatment period.

AB Science

Behaviors and Mental Disorders

Quality of Life

Antibodies

Antibodies, Monoclonal

Immunoglobulins

8 SC injections of 200 mg/1.14 ml of sarilumab over 16 weeks

sarilumab is a fully human anti-IL-6R(number sign) monoclonal antibody that binds membrane-bound and soluble human IL-6R and has been shown to inhibit IL-6 signaling

sarilumab

Hirsh D Komarow, M.D.

Background:

Mast cells help the body fight disease and heal wounds. People with indolent systemic mastocytosis (ISM) make too many mast cells. This causes pain, tiredness, digestive problems, and other symptoms. Researchers think the drug sarilumab could help.

Objective:

To see if sarilumab is a safe and effective treatment for people with ISM.

Eligibility:

Adults ages 18-75 with ISM who are enrolled in NIH study 02-I-0277

Design:

Participants will be screened with:

* Physical exam
* Medical history
* Blood and urine tests
* Questionnaires
* Bone marrow removed by a needle inserted into the hip bone
* Ultrasound of the abdomen
* Photographs of the skin

Participants will repeat some screening tests at study visits.

Participants will have a baseline visit in the hospital for 3 days. They will:

* Be assigned to get either the study drug or a placebo. They will not know which one they get.
* Have a skin punch biopsy: An instrument will remove a small piece of skin.
* Get their first drug dose injected under their skin

Participants will keep a side effect and medication diary during the study.

Participants will visit the clinic to get a drug dose every 2 weeks, for a total of 8 doses.

Participants will have a visit 2 weeks after their final dose. It will last up to 2 days.

Participants will have another visit 12 weeks later.

Participants may then continue this study for 1 more year. Those who continue will get sarilumab, even if they previously got the placebo, every 2 weeks. They will have visits every 6 weeks, and then every 3 months.

Systemic mastocytosis is a disorder caused by clonal mast cell proliferation and release of mast cell mediators including tryptase. As a result, mast cell numbers may increase and affect target organs including the dermis (maculopapular cutaneous mastocytosis/urticaria pigmentosa, flushing), gastrointestinal tract (abdominal pain, diarrhea), skeletal system (osteoporosis), hematological system (anemia, thrombocytopenia), and spleen and liver (organomegaly). Patients with indolent (non-aggressive) systemic mastocytosis (ISM) are not candidates for cytoreductive therapy and are generally treated with symptomatic therapy that only partly decreases symptoms. There is, however, a documented association between severity of mastocytosis and elevated serum levels of interleukin (IL)-6. Furthermore, mast cells have been shown to double their rate of division and exhibit increased reactivity and release of mediators when cultured in the presence of IL-6. In addition, in an animal model of mastocytosis, anti-IL-6 has been shown to slow disease progression. In this study, adults with ISM will thus be randomized and treated with sarilumab, a recombinant monoclonal antibody directed against the IL-6 receptor, or receive placebo. Sarilumab is marketed in the United States as Kevzara (Sanofi/Genzyme \[Cambridge, MA, USA \]) and is approved by the Food and Drug Administration for the treatment of rheumatoid arthritis. Binding of sarilumab to the IL-6 receptor inhibits IL-6-associated human mast cell signaling and proliferation with a resultant decrease in proliferation and reactivity (decreased mediator release), and therefore is a rational choice for the treatment of ISM.

In this study, participants will be randomized with approximately half of the participants receiving study drug, which will be administered at 200 mg via subcutaneous (SC) injection once every 2 weeks (Q2W) for a total of 16 weeks. The other participants will receive a placebo administered via SC injection Q2W for 16 weeks. Participants will return for a follow-up visit 2 weeks after the final dose (treatment peak), and then again 12 weeks later. Evaluations at study visits will include quality of life and symptom assessments and measurement of serum tryptase levels. Bone marrow examination will be performed at the onset and conclusion of the study. After the week 28 visit, all participants will have the option to continue sarilumab for 52 more weeks, at 200 mg administered via SC injections. Participants will continue to be monitored on a regular basis for safety concerns, as instructed in the study drug s package insert.

Safety and Efficacy of Subcutaneous Sarilumab in Improving the Quality of Life in People With Indolent Systemic Mastocytosis

A Phase 2 Randomized Double-Blinded Placebo-Controlled Study to Evaluate the Safety and Efficacy of Subcutaneous Sarilumab in Improving the Quality of Life in Subjects With Indolent Systemic Mastocytosis

QoL at 16 weeks post-initiation of study drug/placebo using the Mastocytosis Quality of Life Questionnaire (MC-QoL)

frequency and severity of adverse events during the randomized double-blinded placebo-controlled treatment period

Reduction in use of medicines for symptomatic relief, reduction in serum levels of tryptase

Percent improvement in QoL using MC-Qol, scoring of mastocytosis index (SCORMA), and Memorial Symptom Assessment Scale (MSAS) and the Mastocytosis Quality of Life Questionnaire (MQLQ), and the mastocytosis Symptom Assessment Form (MSAF)

Reduction of percentage infiltrating mast cells in bone marrow. Decrease in the allelic frequency of D816V using PCR

National Institute of Allergy and Infectious Diseases (NIAID)

Blood and Lymph Conditions

Nervous System Diseases

Leukemia

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Preleukemia

Leukemia, Myelomonocytic, Chronic

Leukemia, Myelomonocytic, Juvenile

Myelodysplastic Syndromes

Hematologic Neoplasms

Myeloproliferative Disorders

Aggression

Soft Tissue Neoplasms

Hematologic Diseases

Leukemia, Mast-Cell

Urticaria Pigmentosa

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

Acute Graft Versus Host Disease

Chronic Myeloproliferative Disorders

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

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Mast Cell Activation Test in Allergic Disease	NCT03406325	Asthma Mastocytosis Mast Cell Activ... Food Allergy Chronic Idiopat... Anaphylaxis Eczema		18 Years -	Hong Kong Sanatorium & Hospital
Imatinib in KIT-negative Systemic Mastocytosis	NCT01297777	Systemic Mastoc...	Imatinib Mesyla...	18 Years -	Hospital Virgen de la Salud
Mast Cell Activation Test in Allergic Disease	NCT03406325	Asthma Mastocytosis Mast Cell Activ... Food Allergy Chronic Idiopat... Anaphylaxis Eczema		18 Years -	Hong Kong Sanatorium & Hospital
Masitinib in Severe Indolent or Smoldering Systemic Mastocytosis Unresponsive to Optimal Symptomatic Treatment	NCT04333108	Indolent System...	Masitinib Placebo Best Supportive...	18 Years - 75 Years	AB Science
Safety and Efficacy of Subcutaneous Sarilumab in Improving the Quality of Life in People With Indolent Systemic Mastocytosis	NCT03770273	Indolent System...	sarilumab Placebo	18 Years - 75 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.
Imatinib in KIT-negative Systemic Mastocytosis	NCT01297777	Systemic Mastoc...	Imatinib Mesyla...	18 Years -	Hospital Virgen de la Salud
Masitinib in Severe Indolent or Smoldering Systemic Mastocytosis	NCT00814073	Indolent System...	Masitinib Placebo Best Supportive...	18 Years - 75 Years	AB Science

Spots Global Cancer Trial Database for mast cell

Every month we try and update this database with for mast cell cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for mast cell

Every month we try and update this database with for mast cell cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for mast cell cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.