Mastocytosis

Researchers are investigating CGT9486 (bezuclastinib) in a Phase 2 open-label study for adults with Advanced Systemic Mastocytosis (AdvSM), including Aggressive Systemic Mastocytosis (ASM), Systemic Mastocytosis with an Associated Hematologic Neoplasm (SM-AHN), and Mast Cell Leukemia (MCL). This study aims to evaluate the drug's safety, efficacy, pharmacokinetics, and pharmacodynamics in these conditions. Participants receive bezuclastinib tablets taken orally in continuous 28-day cycles. The study has two parts conducted over 18 months each: Part I focuses on identifying active and tolerable doses, while Part II assesses treatment effectiveness by measuring the modified IWG Objective Response Rate (ORR) and confirms exposure-response relationships. During the study, participants will undergo evaluations including blood and bone marrow tests, imaging for spleen and liver size, and monitoring of mutation levels and serum tryptase. Researchers will track adverse events, duration and time to response, progression-free and overall survival. The total study duration includes these assessments over 18 months.

Researchers are studying the effects of elenestinib (BLU-263) combined with symptom directed therapy (SDT) compared to placebo plus SDT in adults with indolent systemic mastocytosis (ISM) who have symptoms not well controlled by current treatments. This randomized, double-blind, placebo-controlled Phase 2/3 trial includes participants with ISM and smoldering systemic mastocytosis (SSM), aiming to evaluate both safety and efficacy of the treatments. The study is sponsored by Blueprint Medicines Corporation and includes participants who have previously used selective KIT inhibitors as well as pharmacokinetic groups. Participants will be assigned to receive either elenestinib or placebo along with symptom directed therapies tailored individually. Elenestinib is taken orally once daily. The study is organized into multiple parts: Parts 1 and 2 involve treatment periods lasting up to approximately 48 weeks, after which participants in Part 2 may continue into Part 3 and receive open-label elenestinib for up to five years. Part K enrolls those previously treated with KIT inhibitors. Symptom directed therapy doses are stabilized before treatment and maintained throughout. During the trial, participants will be monitored regularly for side effects and symptom changes using the ISM-Symptom Assessment Form (ISM-SAF) and other measures such as serum tryptase levels, KIT D816V allele fraction, bone marrow mast cell counts, and quality of life assessments. Safety will be tracked through adverse event reporting. The study duration can extend up to five years, allowing long-term evaluation of treatment effects and symptom control. Participants will have ongoing evaluations at set intervals including baseline, weeks 13, 24, 48, and beyond as applicable.

Researchers are studying familial hypereosinophilia (FE), a hereditary form of hypereosinophilic syndrome (HES) characterized by elevated eosinophil levels that can damage organs such as the heart and nerves. This observational study aims to understand the natural history, genetic causes, and disease markers of FE by enrolling about 50 individuals from a previously studied family, including both affected and unaffected members. Participants will be categorized into groups based on whether they have peripheral blood eosinophilia. They will undergo yearly clinical evaluations including medical history, physical exams, bloodwork, EKG, echocardiograms, and lung function tests. Adult participants will provide bone marrow samples at the start, and some adults may also participate in leukapheresis sessions where blood is processed to separate components for research. Unaffected family members will provide specimens to help identify genetic causes. Throughout the study, participants will donate blood and tissue samples for research. Assessments include monitoring for eosinophil-related organ damage and immunologic and molecular features of the disease. The primary outcome is the development of eosinophilic end organ manifestations over 30 years. Safety and therapy needs will be managed by clinicians, and the study follows participants indefinitely to track disease progression and markers.

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 MGD024, a new drug for adults with certain blood cancers that have not responded to standard treatments or have returned after treatment. This Phase 1 trial aims to understand the safety, how the drug acts in the body, immune reactions, and early signs of its effect against these blood cancers. The study is open-label and conducted at multiple centers for patients with select relapsed or refractory hematologic malignancies. Participants will receive MGD024 in cycles lasting 28 days each, for up to 12 cycles or about one year, unless they need to stop earlier. The dose of MGD024 may increase based on safety and tolerability. Response to treatment will be checked after the first cycle and then every two cycles. The drug is designed to target cancer cells expressing CD123 and help the immune system attack them. Throughout the study, participants will be monitored closely for side effects and treatment responses. Assessments include measuring severe side effects during the first 28 days and ongoing tracking of adverse events for up to 12 months. Researchers will also study drug levels in the body, immune reactions, and cancer response rates over time. Participants can expect regular check-ups and tests to evaluate safety and effectiveness during the trial period.

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 I/II 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.

Researchers are studying how eosinophils, a type of white blood cell, become activated and their role in immune reactions. Eosinophils often increase with allergies, asthma, parasitic infections, some autoimmune diseases, and rarely tumors, a condition called eosinophilia. While usually without symptoms, eosinophilia can sometimes cause swelling, itching, lung problems, heart disease, or nerve damage due to toxic substances released by these cells. Participants with eosinophil counts above 750/ml or abnormal eosinophil buildup in tissues or skin will have thorough medical exams, blood tests, and possibly additional tests based on age and symptoms. This observational study does not offer experimental treatments but monitors clinical responses and collects blood, bone marrow, tissue, and fluid samples for research. Follow-up includes yearly evaluations and may involve bone marrow biopsies, genetic testing, and leukapheresis for adults. Participants will be involved in detailed clinical evaluations at baseline and annually, with sample collections to study disease mechanisms and immune responses. The study aims to identify causes, biomarkers, and treatment effects on eosinophils. Safety monitoring includes standard care for those needing treatment, while research focuses on immune cell behavior, genetic factors, and long-term effects. Participation duration varies per individual, with ongoing assessments of disease activity and patient-reported outcomes.

This observational study focuses on adults diagnosed with Indolent Systemic Mastocytosis (ISM), aiming to gather detailed information about the clinical features, outcomes, and medical care of people living with ISM in everyday settings. The research will explore demographic and clinical aspects including episodes of anaphylaxis and bone-related issues. Participants' quality of life and how well their disease is controlled will be assessed through questionnaires. The study includes participants who are currently receiving or plan to receive treatments directed at ISM symptoms, including the medication avapritinib. As an observational study, there are no assigned treatments or placebos; instead, researchers will monitor participants' real-world management of ISM over time. Participants will be involved for up to 61 months, during which their baseline characteristics will be recorded. Researchers will regularly collect patient-reported outcomes, blood samples to measure specific markers like serum KIT D816V variant allele frequency and serum tryptase levels, and track changes in symptom-directed therapies. This long-term monitoring helps understand how ISM and its treatments affect patients over time, along with safety and disease progression.

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 Behçet's disease, Still disease, Schnitzler's 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.