What is the mechanism of action of this treatment?

Tyrosine Kinase Inhibitors (TKIs) like Avapritinib work by selectively targeting and inhibiting specific tyrosine kinases, which are enzymes involved in the signaling pathways that regulate cell division and survival. In the context of Systemic Mastocytosis (SM), these kinases, particularly the KIT mutation, play a crucial role in the proliferation and accumulation of mast cells. By inhibiting these kinases, TKIs can reduce the abnormal growth and activity of mast cells, thereby alleviating symptoms and improving the quality of life for patients with SM. This targeted approach is significant because it directly addresses the underlying genetic mutations driving the disease, offering a more effective and specific treatment option compared to broader therapies.

What side effects are associated with this type of intervention?

Common side effects of Tyrosine Kinase Inhibitors (TKIs) like Avapritinib, used in the treatment of Systemic Mastocytosis, include gastrointestinal issues (nausea, vomiting, diarrhea), fatigue, edema, and cytopenias (anemia, thrombocytopenia). Patients may also experience headaches, dizziness, and liver enzyme abnormalities. It is important to monitor for these side effects and manage them appropriately in consultation with a healthcare provider.

What prior FDA approvals exist?

The FDA has approved several treatments for Systemic Mastocytosis, particularly focusing on Tyrosine Kinase Inhibitors (TKIs). Midostaurin (Rydapt) was the first TKI approved for the treatment of advanced systemic mastocytosis, including aggressive systemic mastocytosis, systemic mastocytosis with associated hematological neoplasm, and mast cell leukemia. Avapritinib, another TKI, is currently being studied for its efficacy and safety in treating indolent systemic mastocytosis, as it targets specific KIT mutations associated with the disease. These treatments aim to manage symptoms and improve quality of life for patients with systemic mastocytosis.

What other types of research exist?

Promising alternatives to Avapritinib for Systemic Mastocytosis patients may include other tyrosine kinase inhibitors such as midostaurin, which is already approved for advanced SM. Additionally, emerging therapies in clinical trials, such as other selective TKIs or novel agents targeting different pathways involved in mast cell proliferation and activation, could be considered. Consulting with a healthcare provider for the latest clinical trial data and treatment options is recommended.

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Tyrosine Kinase Inhibitor

Avapritinib for Systemic Mastocytosis

Phase 2

Waitlist Available

Research Sponsored by Blueprint Medicines Corporation

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

For patients receiving corticosteroids, the dose must be ≤ 20 mg/d prednisone or equivalent, and the dose must be stable for ≥ 14 days.

Patient must have SM, confirmed by Central Pathology Review of BM biopsy, and central review of B- and C-findings by WHO diagnostic criteria.

Must not have

Patient must not have received prior treatment with avapritinib.

Patient has been diagnosed with any of the following WHO SM subclassifications: cutaneous mastocytosis only, smoldering SM, SM with associated hematologic neoplasm, aggressive SM, mast cell leukemia, or mast cell sarcoma.

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 5 years

Summary

This trial is testing a new medication called avapritinib combined with the best possible care for patients with a condition called indolent systemic mastocytosis (ISM). These patients have symptoms that are not well managed by their current treatments. Avapritinib works by blocking certain proteins that cause abnormal cell growth and activity, aiming to improve symptom control.

Who is the study for?

This trial is for patients with indolent systemic mastocytosis (ISM) who haven't found relief from their symptoms through standard care. They must have a specific symptom score, confirmed ISM by pathology review, and be able to perform daily activities with minimal assistance. People can't join if they've had certain treatments recently, other SM subtypes, prior avapritinib use, or specific heart rhythm issues.

What is being tested?

The study tests Avapritinib's effectiveness and safety against a placebo in ISM patients whose symptoms persist despite best supportive care. It's randomized and double-blind: neither doctors nor participants know who gets the real drug or placebo until the study ends. Everyone eventually receives Avapritinib during part three of the trial.

What are the potential side effects?

While not specified here, side effects of Avapritinib may include nausea, vomiting, swelling around eyes or mouth; skin rash; shortness of breath; feeling dizzy or faint; rapid heartbeat; weight gain due to fluid retention.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I am on a stable dose of corticosteroids, not exceeding 20 mg/d prednisone or its equivalent, for at least 14 days.

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My systemic mastocytosis was confirmed by a specialized lab review.

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My symptoms are moderate to severe based on a recent symptom score.

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I am able to care for myself and perform daily activities.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have never been treated with avapritinib.

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I have been diagnosed with a specific type of mast cell disorder.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 5 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 5 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 5 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Part 2: Mean change in ISM Symptom Assessment Form (ISM-SAF) total symptom score (TSS) as compared to placebo

Secondary study objectives

Parts 1, 2, and 3: Change in 12-item Short Form Health Survey (SF-12)

Parts 1, 2, and 3: Change in EuroQuol 5 Dimensions 5 Levels (EQ 5D-5L)

Parts 1, 2, and 3: Change in Patients' Global Impression of Change (PGIC)

+1 more

Side effects data

From 2023 Phase 4 trial • 2 Patients • NCT04825574

50%

Gastrointestinal haemorrhage

50%

Arthralgia

50%

Abdominal pain

50%

Vomiting

100%

80%

60%

40%

20%

Study treatment Arm

Avapritinib

Trial Design

7Treatment groups

Experimental Treatment

Placebo Group

Group I: (Part 3) Avapritinib RP2D + BSCExperimental Treatment1 Intervention