What side effects are associated with this type of intervention?

Common treatments for Systemic Mastocytosis, particularly those targeting mast cell activation and proliferation like BLU-263, often include tyrosine kinase inhibitors (TKIs). Known side effects of these treatments can include gastrointestinal issues (nausea, vomiting, diarrhea), fatigue, headache, and potential liver enzyme abnormalities. Additionally, some patients may experience skin reactions, edema, and cytopenias (reduced blood cell counts). It is important for patients to discuss these potential side effects with their healthcare provider to manage and mitigate them effectively.

What prior FDA approvals exist?

The FDA has approved several treatments for systemic mastocytosis, focusing on inhibiting mast cell activation and proliferation. One notable drug is midostaurin (Rydapt), a multi-kinase inhibitor that targets KIT D816V mutation, commonly found in systemic mastocytosis. Other treatments include cladribine and interferon-alpha, which are used for more aggressive forms of the disease. These treatments aim to reduce mast cell burden and alleviate symptoms, similar to the investigational drug BLU-263 being studied for indolent systemic mastocytosis.

What other types of research exist?

Promising novel alternatives to BLU-263 for Systemic Mastocytosis patients include avapritinib and midostaurin. Both are tyrosine kinase inhibitors that have shown efficacy in treating SM by targeting the KIT D816V mutation, which is commonly associated with the disease. Additionally, ongoing research and clinical trials may reveal new therapeutic options in the near future.

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Kinase Inhibitor

BLU-263 for Systemic Mastocytosis

Phase 2 & 3

Recruiting

Research Sponsored by Blueprint Medicines Corporation

Eligibility Criteria Checklist

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

Must have

Patients must have symptoms consistent with mast cell activation (despite BSC) in at least two organ systems characterized by cutaneous flushing, tachycardia, syncope, hypotension, diarrhea, nausea, vomiting and gastro-intestinal cramping) and serum blood tryptase (sBT) levels above 8 ng/mL OR Severe (Ring and Messmer grading ≥ II, recurrent anaphylaxis, including but not limited to hymenoptera venom, drug or food, regardless of sBT levels.

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

Must not have

Patient has organ damage C-findings attributable to SM.

Patient has clinically significant, uncontrolled, cardiovascular disease

Timeline

Screening 3 weeks

Treatment Varies

Follow Up baseline up to 4 years

Summary

This trial tests BLU-263 combined with the best possible care for patients with specific conditions whose symptoms are not well-controlled. The medication aims to reduce symptoms by blocking overactive cells.

Who is the study for?

This trial is for patients with indolent systemic mastocytosis (ISM) who still have symptoms despite best supportive care. They should have a blood tryptase level above 8 ng/mL or severe reactions to allergens, an ECOG Performance Status of 0-2, and not controlled symptoms after trying at least two therapies like antihistamines or corticosteroids. People can't join if they've had certain heart issues, other myeloproliferative disorders, recent cancer treatments outside of specific exceptions, or previous treatment with targeted KIT inhibitors.

What is being tested?

The HARBOR study is testing the effectiveness and safety of BLU-263 compared to a placebo in managing ISM symptoms. Participants will receive either BLU-263 plus best supportive care or a placebo plus best supportive care in a randomized and double-blind setup. After completing initial phases, all participants may receive BLU-263 openly.

What are the potential side effects?

While the side effects of BLU-263 are not detailed here, typical drug-related side effects could include digestive issues, skin reactions, headaches, fatigue and potential allergic responses. The exact profile will be monitored throughout the trial.

Eligibility Criteria

Inclusion Criteria

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

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I experience symptoms like flushing, rapid heartbeat, fainting, low blood pressure, diarrhea, nausea, vomiting, or stomach cramps in at least two parts of my body and have high tryptase levels or severe reactions to things like insect stings, medications, or foods.

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

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My tests show I have KIT D816V or CD25+ Mast cells.

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I can take care of myself and am up and about more than half of my waking hours.

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

Exclusion Criteria

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

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My organ damage is due to systemic mastocytosis.

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I have a serious heart condition that is not under control.

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I have been treated with drugs targeting the KIT protein.

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I have been diagnosed with a blood disorder related to myeloproliferative disease.

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I have been diagnosed with a specific type of systemic mastocytosis.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ baseline up to 4 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~baseline up to 4 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and baseline up to 4 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

Parts 1 and 3: Mean change from baseline in ISM-SAF TSS

Secondary study objectives

Part 2: Mean change from baseline in ISM-SAF

Parts 1, 2, and 3: Mean change from baseline in ISM-SAF individual symptom scores

Parts 1, 2, and 3: Time to achieve 30% reduction from baseline in ISM-SAF scores

+1 more

Other study objectives

Mast cell

Trial Design

10Treatment groups

Experimental Treatment

Placebo Group

Group I: PK Groups (Dose 2 or Dose 3)Experimental Treatment1 Intervention

Patients will receive BSC and Dose 2 or Dose 3 of elenestinib. BSC will be determined on a per patient basis. Elenestinib will be administered orally for the duration of participation in the study.

Group II: (Part S) Elenestinib + BSCExperimental Treatment1 Intervention

Participants with Smoldering Systemic Mastocytosis (SSM) will receive open-label BSC and elenestinib for up to approximately 4 years.

Group III: (Part M) Elenestinib RD + BSCExperimental Treatment1 Intervention

Patients will receive BSC and the RD of elenestinib. BSC will be determined on a per patient basis. Elenestinib will be administered orally, once daily for the duration of participation in the study.

Group IV: (Part 3) Elenestinib RD + BSCExperimental Treatment1 Intervention

Patients will receive open-label BSC and the RD of elenestinib for up to approximately 4 years.

Group V: (Part 2) Elenestinib RD + BSCExperimental Treatment1 Intervention

Patients will receive BSC and the recommended dose (RD) of elenestinib. BSC will be determined on a per patient basis. Elenestinib will be administered orally, once daily for approximately 24 weeks

Group VI: (Part 1) Elenestinib Dose 3 + BSCExperimental Treatment1 Intervention

Patients will receive BSC and Dose 3 of elenestinib. BSC will be determined on a per patient basis. Elenestinib will be administered orally, once daily until completion of Part 1.

Group VII: (Part 1) Elenestinib Dose 2 + BSCExperimental Treatment1 Intervention

Patients will receive BSC and Dose 2 of elenestinib. BSC will be determined on a per patient basis. Elenestinib will be administered orally, once daily until completion of Part 1.

Group VIII: (Part 1) Elenestinib Dose 1 + BSCExperimental Treatment1 Intervention

Patients will receive best supportive care (BSC) and Dose 1 of elenestinib. BSC will be determined on a per patient basis. Elenestinib will be administered orally, once daily until completion of Part 1.

Group IX: (Part 2) Placebo + BSCPlacebo Group1 Intervention

Patients will receive BSC and matching placebo. BSC will be determined on a per patient basis. Placebo will be administered orally, once daily once daily for approximately 24 weeks

Group X: (Part 1) Placebo + BSCPlacebo Group1 Intervention

Patients will receive BSC and matching placebo. BSC will be determined on a per patient basis. Placebo will be administered orally, once daily until completion of Part 1

0 / 10Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Systemic mastocytosis is primarily treated by targeting mast cell activation and proliferation. Treatments like BLU-263 work by inhibiting the activity of KIT, a receptor tyrosine kinase that plays a crucial role in mast cell growth and survival. By blocking KIT signaling, these treatments reduce the number of mast cells and their release of inflammatory mediators, thereby alleviating symptoms such as itching, abdominal pain, and anaphylaxis. This is particularly important for patients whose symptoms are not adequately controlled by best supportive care alone, as it directly addresses the underlying pathophysiology of the disease.

Treatment of CD30-positive systemic mastocytosis with brentuximab vedotin.