534 Participants Needed

BLU-263 for Systemic Mastocytosis

Recruiting at 57 trial locations
SH
SP
CR
TR
KT
MH
NJ
IB
Overseen ByIlda Bidollari
Age: 18+
Sex: Any
Trial Phase: Phase 2 & 3
Sponsor: Blueprint Medicines Corporation
Must be taking: H1 blockers, H2 blockers
Prior Safety DataThis treatment has passed at least one previous human trial

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines a new treatment called elenestinib (BLU-263) for individuals with indolent systemic mastocytosis (ISM), a condition where certain immune cells accumulate and cause symptoms like skin rashes and abdominal pain. The goal is to determine if elenestinib can better control these symptoms compared to a placebo, especially for those whose current treatments are insufficient. Participants will receive either elenestinib or a placebo, alongside their usual symptom treatments. This trial may suit individuals with ISM whose symptoms are not well-managed by current therapies like antihistamines or corticosteroids. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to potentially benefit from a promising new therapy.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop all current medications, but it does require that your current symptom management medications are stable for at least 14 days before starting. If you're on corticosteroids, the dose must be 20 mg/d or less and stable for at least 14 days. Some specific treatments like cytoreductive therapy must be stopped for a certain period before screening.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that elenestinib, the treatment under study for systemic mastocytosis, is generally safe. Earlier studies found that it lowers the number of mast cells (immune cells that can cause symptoms when they accumulate) and improves symptoms. Importantly, these studies suggest that patients tolerate elenestinib well.

One study found that elenestinib might be safer than traditional treatments for this condition. Some side effects have been reported, but they are usually manageable, meaning mild issues may occur, but serious problems are less common.

Elenestinib is currently being tested in later stages of clinical trials, which often provide more detailed information about its safety in humans. This phase of testing typically follows earlier studies that have shown the treatment is safe enough for larger groups.12345

Why do researchers think this study treatment might be promising for systemic mastocytosis?

Researchers are excited about elenestinib for systemic mastocytosis because it offers a novel approach compared to current treatments. Most existing options, like antihistamines or tyrosine kinase inhibitors, focus on managing symptoms or targeting specific enzymes. Elenestinib stands out by specifically targeting the KIT D816V mutation, which is a common driver of systemic mastocytosis. This targeted action promises a more precise treatment strategy, potentially leading to better outcomes with fewer side effects. Additionally, elenestinib is taken orally, making it a convenient option for long-term management.

What evidence suggests that this trial's treatments could be effective for indolent systemic mastocytosis?

Research has shown that elenestinib, a new medication, holds potential for treating indolent systemic mastocytosis (ISM). Studies have found that it can reduce the number of problematic mast cells, potentially improving symptoms for those affected. Participants in this trial may receive elenestinib at various doses, while others will receive a placebo. Patients who previously used elenestinib reported symptom relief, and it has been generally safe. Experts believe it could offer a more effective and safer option compared to older treatments. This medication specifically targets a common mutation in systemic mastocytosis, which might lead to better symptom control.12356

Are You a Good Fit for This Trial?

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.

Inclusion Criteria

My symptoms didn't improve after trying at least two different treatments.
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.
My bone marrow biopsy confirms I have ISM according to WHO criteria.
See 9 more

Exclusion Criteria

My organ damage is due to systemic mastocytosis.
I have a serious heart condition that is not under control.
I have been treated with drugs targeting the KIT protein.
See 6 more

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Part 1

Participants receive BSC and various doses of elenestinib or placebo until completion of Part 1

24 weeks

Treatment Part 2

Participants receive BSC and the recommended dose of elenestinib or placebo for approximately 24 weeks

24 weeks

Open-label Treatment Part 3

Participants receive open-label BSC and elenestinib for up to approximately 4 years

Up to 4 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

  • BLU-263
  • Placebo
Trial Overview 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.
How Is the Trial Designed?
10Treatment groups
Experimental Treatment
Placebo Group
Group I: (Part S) Elenestinib Dose 1 + SDTExperimental Treatment1 Intervention
Group II: (Part K) Elenestinib Dose 1 + SDTExperimental Treatment1 Intervention
Group III: (Part 3) Elenestinib + SDTExperimental Treatment1 Intervention
Group IV: (Part 2) Elenestinib Dose 1 + SDTExperimental Treatment1 Intervention
Group V: (Part 1) Elenestinib Dose 3 + SDTExperimental Treatment1 Intervention
Group VI: (Part 1) Elenestinib Dose 2 + SDTExperimental Treatment1 Intervention
Group VII: (Part 1) Elenestinib Dose 1 + SDTExperimental Treatment1 Intervention
Group VIII: (PK groups) Elenestinib + SDTExperimental Treatment1 Intervention
Group IX: (Part 1) Placebo + SDTPlacebo Group1 Intervention
Group X: (Part 2) Placebo + SDTPlacebo Group1 Intervention

Find a Clinic Near You

Who Is Running the Clinical Trial?

Blueprint Medicines Corporation

Lead Sponsor

Trials
31
Recruited
6,000+

Published Research Related to This Trial

A study of 71 patients with systemic mastocytosis (SM) used multi-parameter flow cytometry (MFC) to identify dysplastic traits that can help predict patient outcomes, revealing two distinct groups with significantly different clinical features and survival rates.
Patients classified as MFC+ had shorter survival compared to MFC- patients, and the MFC score was found to be a valuable prognostic tool even in less advanced cases, suggesting that combining MFC analysis with high-risk mutation profiles can enhance prognosis assessment.
Myelodysplasia as assessed by multiparameter flow cytometry refines prognostic stratification provided by genotypic risk in systemic mastocytosis.Mannelli, F., Gesullo, F., Rotunno, G., et al.[2020]
In a phase I trial of avapritinib for advanced systemic mastocytosis, 72% of patients showed a positive response, with 56% achieving complete or partial responses, indicating strong efficacy.
The treatment was well-tolerated, with no patients stopping due to adverse events, which were mostly mild to moderate, suggesting a favorable safety profile.
Rapid Responses to Avapritinib (BLU-285) in Mastocytosis.[2019]
Recent research has identified gain-of-function mutations in the KIT protooncogene as a key factor in systemic mastocytosis (SM), leading to the development of targeted therapies that inhibit mutant Kit tyrosine kinase isoforms.
New small molecules, such as dasatinib and AMN107, are being tested in clinical trials, offering hope for more effective treatments for SM compared to traditional cytoreductive agents like interferon-alpha and cladribine, which have limited and transient efficacy.
Novel approaches in the treatment of systemic mastocytosis.Quintas-Cardama, A., Aribi, A., Cortes, J., et al.[2009]

Citations

NCT04910685 | (HARBOR) Study to Evaluate Efficacy and ...This is a randomized, double-blind, placebo-controlled, Phase 2/3 study comparing the efficacy and safety of elenestinib (BLU-263) + symptom directed ...
Elenestinib May Be Safer Than Traditional KIT Inhibitors in ...We expect something similar with elenestinib —it will likely be very effective in treating patients with systemic mastocytosis but it will not ...
Elenestinib, an Investigational, Next Generation KIT D816V ...Elenestinib, an investigational, next generation KIT D816V inhibitor, reduces mast cell burden, improves symptoms, and has a favorable safety profile in ...
Study of Elenestinib (BLU-263) in Advanced Systemic ...The goal of this clinical trial is to evaluate elenestinib (BLU-263) in participants with Advanced Systemic Mastocytosis (AdvSM), SM with an associated ...
HARBOR: An Ongoing Phase 2/3 Study of Elenestinib in ...HARBOR (NCT04910685) is an ongoing, randomized, double-blind, placebo-controlled, phase 2/3 efficacy and safety study of oral elenestinib in patients with ISM ...
Elenestinib, an Investigational, Next Generation KIT D816V ...ISM, indolent systemic mastocytosis; MC, mast cell; SM, systemic mastocytosis. ... Data cut off date October 17, 2022. AE, adverse event; SAE, serious ...
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