Mastocytosis

Researchers are investigating CGT9486, also known as bezuclastinib, in an open-label Phase 2 study for patients with Advanced Systemic Mastocytosis AdvSM. This includes those diagnosed with Aggressive Systemic Mastocytosis ASM, Systemic Mastocytosis with an Associated Hematologic Neoplasm SM-AHN, and Mast Cell Leukemia MCL. The study aims to evaluate the safety, effectiveness, pharmacokinetics, and pharmacodynamics of bezuclastinib in this patient population. Participants will receive bezuclastinib tablets orally, taken continuously in 28-day cycles. The study is divided into two parts Part I focuses on identifying effective and tolerable dosing exposures over 18 months, while Part II evaluates the drugs efficacy by measuring objective response rates and confirming the exposure-response relationship, also over 18 months. Additional assessments include effects on mutation allele burden, serum tryptase levels, histopathologic changes, spleen and liver volume, and safety monitoring. During the study, participants will undergo various clinical evaluations, including laboratory tests, imaging to monitor organ size changes, and assessments of disease response and progression. Researchers will track adverse events and pharmacokinetic profiles throughout the 18 months. The study involves continuous monitoring of participants to understand the treatments impact on survival and disease progression over this period.

Researchers are evaluating the safety and effectiveness of elenestinib BLU-263 combined with symptom directed therapy SDT compared to placebo plus SDT in adults with indolent systemic mastocytosis ISM whose symptoms are not well controlled by SDT alone. This randomized, double-blind, placebo-controlled Phase 23 study includes multiple parts to assess different doses and durations of elenestinib treatment, including an open-label extension for participants finishing earlier phases. The study also enrolls participants who have previously received an approved selective KIT inhibitor and includes pharmacokinetic groups. Participants receive oral elenestinib or placebo once daily alongside SDT, which is personalized based on individual symptom management needs. Part 1 focuses on short-term treatment lasting up to 12 weeks, while Part 2 extends treatment to approximately 48 weeks. Part 3 and other parts allow treatment for up to about 5 years. The study monitors participants through these phases to evaluate how elenestinib affects symptoms, disease markers, and safety over time. During the study, participants undergo regular assessments of symptoms using the ISM-Symptom Assessment Form ISM-SAF, laboratory tests including serum tryptase and KIT D816V allele levels, bone marrow evaluations, and quality of life measures. Researchers track adverse events and changes in disease-related factors at various points up to 5 years. This thorough monitoring helps measure treatment effects and safety over both short and long-term periods, with total participation lasting several years depending on the study part.

Eosinophils are a type of white blood cell that can cause damage to the heart, nerves, and other organs when their levels are elevated, as seen in hypereosinophilic syndrome HES. Some people have a hereditary form called familial eosinophilia FE. This research aims to study FE, its genetic causes, damage mechanisms, and disease markers to better understand the disease and support the development of less toxic treatments. Approximately 50 adults and children from a family with FE will be enrolled in this long-term study. Participants will undergo yearly clinical exams including medical history, physical exams, blood tests, EKG, echocardiograms, and pulmonary function tests. Adult participants will also donate bone marrow initially, and some will undergo leukapheresis sessions where blood is processed and returned. Both affected and unaffected family members will provide blood and tissue samples for research to help identify genetic and immunologic factors involved in FE. Throughout the study, participants will be regularly evaluated to monitor the natural history of FE and to identify early signs of disease progression. Researchers will measure immunologic and molecular mechanisms, clinical markers, and any organ damage caused by eosinophilia. Medical care for any needed treatment will be provided by clinical services or local doctors. The study is indefinite in duration, with yearly assessments and additional tests as needed.

Researchers are evaluating the effectiveness of avapritinib BLU-285 in treating people with indolent systemic mastocytosis ISM who have symptoms not well controlled by other treatments. This non-interventional study aims to fill gaps in understanding the natural history and management of ISM in real-world settings in Germany. Each participant will be followed for up to 24 months to observe treatment outcomes. Participants will receive avapritinib as an oral tablet prescribed by their healthcare provider, following standard treatment guidelines. The study does not assign treatment but observes participants who are starting avapritinib as part of their usual care. This approach allows researchers to gather data on how avapritinib is used and its effects in typical clinical practice. During the study, participants will undergo assessments including questionnaires to measure quality of life and mastocytosis symptoms at multiple time points up to 24 months. Researchers will collect information on demographics, medical history, medication changes, hospital visits, and safety events such as anaphylaxis. The main outcome is the change in quality of life measured at 6 months, with ongoing monitoring throughout the study period.

Researchers are evaluating the use of Ilaris canakinumab in patients diagnosed with Schnitzlers syndrome to assess how well it works and how safe it is in real-world clinical settings. This observational study focuses on people who are using canakinumab for the first time to treat this rare condition. The study is sponsored by Novartis Pharmaceuticals and aims to gather detailed information about treatment responses and safety outcomes. Participants in this study will be those starting canakinumab treatment for Schnitzlers syndrome as per the approved indications. The study observes patients over time without changing or assigning treatments, registering all diagnosed patients who receive canakinumab, including those who began treatment before the study contract was finalized. It excludes patients previously treated with canakinumab in a specific prior study or those treated for other related inflammatory syndromes or off-label uses. Throughout the study, researchers will monitor patients clinical responses, including complete or partial improvement rates from the first week up to 48 weeks after starting treatment. They will also track various blood markers such as white blood cell counts, neutrophil counts, C-reactive protein levels, alkaline phosphatase, and immunoglobulin levels at multiple time points. Safety is assessed by recording adverse reactions and serious events throughout the observation period. The total study duration extends up to June 2032, allowing long-term follow-up of participants.

Researchers are evaluating the safety, pharmacokinetics, pharmacodynamics, and preliminary effectiveness of an anti-GPRC5D CAR-T cell product called OriCAR-017 in adults with relapsed or refractory multiple myeloma. This Phase III open-label study is the first clinical trial of OriCAR-017 in the United States by OriCell Therapeutics Co., Ltd., aiming to find suitable dosing and assess early treatment results in this patient group. The study includes a Phase I dose escalation stage with three different doses given as a single intravenous infusion to up to 18 participants. This is followed by a dose expansion stage with 10-15 participants and then a Phase II stage that may include up to 48 participants. Each participant receives one infusion of OriCAR-017 to evaluate its effects and safety. Participants will be closely monitored for up to two years after treatment. Researchers will assess the maximum tolerated dose and dose-limiting toxicities within 28 days after infusion. They will also study how the drug moves through and affects the body, measure response duration, progression-free survival, overall survival, and other response rates. Regular evaluations include laboratory tests, clinical assessments, and safety monitoring throughout the study period.

This research aims to understand how eosinophils, a type of white blood cell, become activated and their role in immune responses. Eosinophil counts often increase due to allergies, asthma, parasitic infections, autoimmune conditions, or rarely, tumors. Elevated eosinophil levels, called eosinophilia, usually cause no symptoms but can sometimes lead to swelling, itching, allergic lung problems, heart disease, or nerve damage. Participants with eosinophil counts over 750ml or abnormal eosinophil buildup in skin or tissues, aged 1 to 100 years, will undergo clinical evaluations including medical history, exams, and blood tests. Additional testing may include studies of eyes, lungs, skin, bone marrow, nerves, or heart depending on symptoms and age. This is an observational study without experimental treatments patients needing therapy will get standard care. Some participants may also undergo bone marrow biopsy, genetic testing, or leukapheresis for adults for research purposes. During the study, participants will donate blood samples for laboratory studies and may have annual follow-ups with exams and blood tests to track eosinophil levels and condition changes. Researchers will collect samples like blood, bone marrow, tissue, and body fluids to study disease mechanisms, biomarkers, and treatment responses. The study will monitor clinical and immunological responses to therapy and evaluate family members to explore genetic causes of eosinophilia. The main goal is to better understand eosinophilic disorders and improve diagnosis and treatment options.

Researchers are conducting a Phase 4 observational study to collect detailed information about people with Indolent Systemic Mastocytosis ISM. The study focuses on understanding the clinical features, outcomes, and medical care of ISM in real-world settings. It also aims to describe the demographics and symptoms such as anaphylaxis and bone problems, and assess quality of life and disease control through patient questionnaires. Participants in this study include those currently treated or planning to be treated for ISM, including treatment with avapritinib or other symptom-directed therapies. This is a non-interventional study, meaning treatments are not assigned by the study but are observed as they occur naturally. Data will be collected over time to understand how ISM is managed and how patients respond to treatments. During the study, participants will provide information about their health and treatments through questionnaires and clinical evaluations. Researchers will measure changes in patient-reported outcomes, serum KIT D816V variant allele frequency, serum tryptase levels, and the use of symptom-directed therapies from baseline up to 61 months. The study will continue until December 2032, allowing long-term observation of participants health and treatment effects.

Researchers are investigating the role of IgE proteoforms in various health conditions, including type I allergy, chronic spontaneous urticaria, recent anaphylaxis, mastocytosis, hereditary alpha tryptasemia, X-linked agammaglobulinemia XLA, and in patients undergoing desensitization for venom or medication allergies. The study also includes healthy volunteers to compare findings across these groups. This observational study aims to understand how IgE proteoforms differ among these populations and their potential impact. Participants in this study belong to several groups healthy controls and patients with different allergic or immunological conditions. The study involves collecting blood samples from participants, including those with allergies to medications, venom, food, or airborne allergens, some of whom may be receiving omalizumab treatment. Serial blood sampling is performed to monitor changes over time. During the study, participants will provide blood samples at various time points over four years to evaluate IgE proteoforms. Researchers will collect clinical information regarding allergy severity, medication use, medical history, and laboratory test results. This study involves no treatment interventions and will monitor participants through regular sample collection and clinical assessments to better understand allergy-related immune responses.

Researchers are investigating autoinflammatory diseases AID, which involve recurring inflammatory episodes without infection, cancer, or adaptive immune system problems. This study focuses on both monogenic hereditary periodic syndromes and polygenic or multifactorial AID, including rare conditions like Behets disease, Still disease, Schnitzlers disease, PFAPA syndrome, chronic recurrent multifocal osteomyelitis, non-infectious uveitis and scleritis, among others. The goal is to gather detailed data to improve understanding and management of these rare diseases through an international collaboration. The study uses the AIDA registry, a secure online platform for collecting demographic, genetic, clinical, laboratory, radiologic, and therapeutic information. Data are gathered retrospectively and prospectively during routine clinical visits scheduled every 3-6 months. Eleven registries focus on different AID conditions, enabling comprehensive data collection to identify clinical patterns, treatment impacts, and long-term outcomes over a period of at least 10 years. Participants provide information during their usual care visits, allowing researchers to track changes in disease activity, organ involvement, inflammatory markers, visual function, pain levels, fatigue, fertility, and socioeconomic factors. The study monitors these outcomes over multiple timepoints up to 120 months. Data privacy is ensured by pseudonymizing patient information. This registry supports multiple clinical studies and aims to enhance knowledge, awareness, and future research on autoinflammatory diseases worldwide.