BLU-263 for Systemic Mastocytosis

Recruiting at50 trial locations

Age: Any Age

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2 & 3

Recruiting

Sponsor: Blueprint Medicines Corporation

Must be taking: H1 blockers, H2 blockers

Must not be taking: KIT inhibitors

Disqualifiers: Other myeloproliferative disorders, others

Prior Safety Data

Trial Summary

What is the purpose of this trial?

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.

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.

How is the drug BLU-263 different from other treatments for systemic mastocytosis?

BLU-263 (Elenestinib) is unique because it targets specific mutations in the KIT gene, which are central to the development of systemic mastocytosis, offering a more targeted approach compared to traditional treatments like interferon-alpha and cladribine that have transient effects and work in only some patients. ^{1 2 3 4 5}

Research Team

Eligibility Criteria

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.

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.

Trial Timeline

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

Treatment Details

Interventions

• BLU-263 (Kinase Inhibitor)
• Placebo (Other)

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.

Participant Groups

Group I: PK Groups (Dose 2 or Dose 3) Experimental Treatment 1 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 + BSC Experimental Treatment 1 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 + BSC Experimental Treatment 1 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 + BSC Experimental Treatment 1 Intervention

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

Group V: (Part 2) Elenestinib RD + BSC Experimental Treatment 1 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 + BSC Experimental Treatment 1 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 + BSC Experimental Treatment 1 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 + BSC Experimental Treatment 1 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 + BSC Placebo Group 1 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 + BSC Placebo Group 1 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

Who Is Running the Clinical Trial?

Blueprint Medicines Corporation

Lead Sponsor

Trials

31

Recruited

6,000+

Findings from Research

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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rapid Responses to Avapritinib (BLU-285) in Mastocytosis. [2019]

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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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 study of 73 patients with systemic mastocytosis (SM), those with more aggressive forms of the disease showed increasingly abnormal initial bone scans, indicating that bone scintigraphy can be a useful tool for assessing disease severity.

Patients with scintigraphic progression over time had a poorer prognosis and more aggressive disease, suggesting that monitoring bone scan changes can help predict disease outcomes in SM.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A retrospective analysis of bone scan abnormalities in mastocytosis: correlation with disease category and prognosis. Chen, CC., Andrich, MP., Mican, JM., et al.[2016]

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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel approaches in the treatment of systemic mastocytosis. Quintas-Cardama, A., Aribi, A., Cortes, J., et al.[2009]

Systemic mastocytosis (SM) requires careful risk stratification and integrated management due to its variable manifestations and disease progression, emphasizing the need for a comprehensive approach to treatment.

The development of targeted therapies, particularly those inhibiting the KIT protein, is expanding treatment options for SM, allowing for more personalized therapy based on clinical and molecular characteristics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Catching the clinical and biological diversity for an appropriate therapeutic approach in systemic mastocytosis. Mannelli, F.[2022]

References

1. United States pubmed.ncbi.nlm.nih.gov

Rapid Responses to Avapritinib (BLU-285) in Mastocytosis. [2019]

2. United States pubmed.ncbi.nlm.nih.gov

Myelodysplasia as assessed by multiparameter flow cytometry refines prognostic stratification provided by genotypic risk in systemic mastocytosis. [2020]

3. United States pubmed.ncbi.nlm.nih.gov

A retrospective analysis of bone scan abnormalities in mastocytosis: correlation with disease category and prognosis. [2016]

4. United States pubmed.ncbi.nlm.nih.gov

Novel approaches in the treatment of systemic mastocytosis. [2009]

5. Germany pubmed.ncbi.nlm.nih.gov

Catching the clinical and biological diversity for an appropriate therapeutic approach in systemic mastocytosis. [2022]