Screening for KIT D816V-mutated mast cell disease in selected groups

A Multicenter Screening Study to Characterize the Prevalence of the KIT D816V Mutation in Patients With Suspected Clonal Mast Cell Disease

This screening will test whether people with unexplained anaphylaxis, recurrent mast cell activation symptoms, or conditions like hypermobile EDS or POTS carry the KIT D816V mutation.

Quick facts

• Study type: Observational
• Enrollment: 450 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Blueprint Medicines Corporation (industry)
• Locations: 17 sites (Birmingham, Alabama and 16 other locations)
• Trial ID: NCT07143669 on ClinicalTrials.gov

What this trial studies

This is a multicenter screening effort enrolling two targeted cohorts: people with suspected clonal mast cell activation (unexplained anaphylaxis or episodic symptoms across skin, respiratory, gastrointestinal, or cardiovascular systems) and people with hypermobile Ehlers–Danlos spectrum disorders or postural orthostatic tachycardia syndrome. Participants provide blood or other clinical samples for sensitive molecular testing to detect the KIT D816V mutation. The study characterizes the prevalence of the mutation in these selected populations and links mutation status with clinical presentation. Findings are intended to inform diagnostic pathways and potential referral for mutation-directed care.

Who should consider this trial

Good fit: Ideal candidates are people with suspected clonal mast cell disease—either unexplained anaphylaxis or recurrent mast cell activation symptoms—or people with hypermobile Ehlers–Danlos spectrum disorders or POTS.

Not a fit: People without clinical signs of mast cell activation or whose symptoms are explained by other diagnoses are unlikely to benefit from this mutation screening.

Why it matters

Potential benefit: If successful, this could help identify people with KIT D816V-driven mast cell disease so they can be referred for appropriate genetic counseling and targeted care.

How similar studies have performed: KIT D816V is a well-known driver mutation in systemic mastocytosis and prior molecular screening has identified it in related patient groups, though broad screening in these specific cohorts is less commonly reported.

Eligibility criteria

Key Inclusion Criteria:

* Cohort 1 participants must meet inclusion criteria for either SMAC-A or SMAC-B:

  1\. SMAC-A
* Documented anaphylaxis due to Hymenoptera venom with cardiovascular symptoms or
* Documented anaphylaxis without known trigger(s) or allergen(s) warranting hospitalization, emergency room visit, and/or epinephrine with cardiovascular symptoms 2. SMAC-B
* Episodic or recurrent signs and symptoms consistent with mast cell activation without known triggers or allergens in at least 2 of the following organ systems: skin, respiratory/naso-ocular, gastrointestinal tract, or cardiovascular.
* Any clinical response on one or more optimally dosed therapies intended to mitigate mast cell mediators, as determined by the Investigator.
* Cohort 2 participants must have confirmed, known diagnosis of 1 of the following criteria:

  1. Either hypermobile Ehlers-Danlos syndrome or documented history of hypermobility spectrum disorder.
  2. Postural orthostatic tachycardia syndrome with one or more systemic symptoms.
  3. Early onset (≤50 years old) osteoporosis or osteopenia.
* Cohort 3 participants must have documented diagnosis of 1 of the following, according to World Health Organization 5th edition criteria: chronic myelomonocytic leukemia or myelodysplastic syndrome/myeloproliferative neoplasm not otherwise specified.

Key Exclusion Criteria:

* Participants previously diagnosed with any of the following:

  1. Monoclonal mast cell activation syndrome with a known KIT mutation
  2. Cutaneous mastocytosis only (that is, no documentation of systemic mast cell disease via bone marrow biopsy)
  3. Any subtype of systemic mastocytosis
  4. Mast cell sarcoma
* Cohort 2 only: Osteopenia or osteoporosis attributed to known genetic, endocrine, nutritional, or other medical conditions.

Note: Additional protocol-defined criteria apply.

Where this trial is running

Birmingham, Alabama and 16 other locations

• AllerVie Clinical Research — Birmingham, Alabama, United States (RECRUITING)
• O'Neal Comprehensive Cancer Center at the UAB — Birmingham, Alabama, United States (RECRUITING)
• Kaiser Permanente San Diego — San Diego, California, United States (RECRUITING)
• Allergy & Asthma Clinical Research of the Bay Area — Walnut Creek, California, United States (RECRUITING)
• Allergy, Asthma, & Immunology Associates of Tampa Bay — Tampa, Florida, United States (RECRUITING)
• Emory University — Atlanta, Georgia, United States (RECRUITING)
• Midwest Allergy Sinus Asthma — Normal, Illinois, United States (RECRUITING)
• Tulane University School of Medicine — New Orleans, Louisiana, United States (RECRUITING)
• AllerVie Health — Glenn Dale, Maryland, United States (RECRUITING)
• Barnes-Jewish West County Hospital — St Louis, Missouri, United States (RECRUITING)
• Somnos Clinical Research — Lincoln, Nebraska, United States (RECRUITING)
• Mount Sinai Hospital — New York, New York, United States (RECRUITING)
• The University of North Carolina at Chapel Hill — Chapel Hill, North Carolina, United States (RECRUITING)
• Allergy, Asthma & Clinical Research Center — Oklahoma City, Oklahoma, United States (RECRUITING)
• Allergy & Clinical Immunology Associates — Pittsburgh, Pennsylvania, United States (RECRUITING)
• Care Access Research — Warwick, Rhode Island, United States (RECRUITING)
• AIR Care — Dallas, Texas, United States (RECRUITING)

Study contacts

• Study coordinator: Blueprint Medicines

Conditions: Clonal Mast Cell Disease, KIT D816V Mutation, Suspected KITD816V Mutated Clonal Mast Cell Disease, Mast Cell Activation Disorder, MDS/MPN Overlap Syndrome, Chronic Myelomonocytic Leukemia, Hypermobility Syndrome Disorder, Postural Orthostatic Tachycardia Syndrome