(HARBOR) Study to Evaluate Efficacy and Safety of BLU-263 Versus Placebo in Patients With Indolent Systemic Mastocytosis
Phase 2
Recruiting
- Conditions
- Indolent Systemic MastocytosisSmoldering Systemic Mastocytosis
- Interventions
- Drug: Placebo
- Registration Number
- NCT04910685
- Lead Sponsor
- Blueprint Medicines Corporation
- Brief Summary
This is a randomized, double-blind, placebo-controlled, Phase 2/3 study comparing the efficacy and safety of elenestinib (BLU-263) + symptom directed therapy (SDT) with placebo + SDT in participants with indolent systemic mastocytosis (ISM) whose symptoms are not adequately controlled by SDT. Parts 1 and 2 will enroll participants with ISM. Participants enrolled in Part 2 will roll over onto Part 3 to receive treatment with elenestinib in an open-label fashion following completion of the earlier Part. Part K will enroll participants with ISM who have previously received an approved selective KIT inhibitor. The study also includes pharmacokinetic (PK) groups that will enroll participants with ISM.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 534
Inclusion Criteria
All Participants:
-Participant must have an Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 to 2.
Part 1 and PK groups:
- Participant has confirmed diagnosis of ISM, confirmed by Central Pathology Review
- Participant must have failed to achieve adequate symptom control for 1 or more Baseline symptoms, as determined by the Investigator, with at least 2 of the following symptom-directed therapies administered: H1 blockers, H2 blockers, proton-pump inhibitors, leukotriene inhibitors, cromolyn sodium, corticosteroids, or omalizumab.
- Participants must have SDT for ISM symptom management stabilized for at least 14 days prior to starting screening procedures.
- For participants receiving corticosteroids, the dose must be ≤ 20 mg/day prednisone or equivalent, and the dose must be stable for ≥ 14 days.
Part K:
-Participant has confirmed diagnosis of ISM, confirmed by Central Pathology Review
Part S:
-Participant has confirmed diagnosis of SSM, confirmed by Central Pathology Review of BM biopsy and central review of B- and C-findings by WHO diagnostic criteria.
Part 2:
-Participant has confirmed diagnosis of ISM, confirmed by Central Pathology Review
Key
Exclusion Criteria
- Participant has been diagnosed with any of the following WHO systemic mastocytosis (SM) sub-classifications: cutaneous mastocytosis only, SM with an associated hematologic neoplasm of non-MC lineage (SM-AHN), aggressive SM, mast cell leukemia, or mast cell sarcoma.
- Participant has been diagnosed with another myeloproliferative disorder.
- Participant has organ damage attributable to SM.
- Participant has clinically significant, uncontrolled, cardiovascular disease
- Participant has a QT interval corrected using Fridericia's formula (QTcF) > > 470 milliseconds (msec) (for females) or > 450 msec (for males).
- Participant has a history of a primary malignancy that has been diagnosed or required therapy within 3 years. The following prior malignancies are not exclusionary: completely resected basal cell and squamous cell skin cancer, curatively treated localized prostate cancer, and completely resected carcinoma in situ of any site.
- Time since any cytoreductive therapy including masitinib and midostaurin should be at least 5 half-lives or 14 days (whichever is longer), and for cladribine, interferon alpha, pegylated interferon, or antibody therapy < 28 days or 5 half-lives of the drug (whichever is longer), before beginning the screening period.
- Participant has received radiotherapy or psoralen and ultraviolet A (PUVA) therapy < 14 days before beginning the screening period.
Other protocol-defined criteria apply.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description (Part 1) Elenestinib Dose 1 + SDT Elenestinib Participants will receive SDT and elenestinib. SDT will be determined on a per participant basis. Elenestinib will be administered orally, once daily until completion of Part 1. (Part 1) Elenestinib Dose 2 + SDT Elenestinib Participants will receive SDT and elenestinib. SDT will be determined on a per participant basis. Elenestinib will be administered orally, once daily until completion of Part 1. (Part 1) Elenestinib Dose 3 + SDT Elenestinib Participants will receive SDT and elenestinib. SDT will be determined on a per participant basis. Elenestinib will be administered orally, once daily until completion of Part 1. (Part 1) Placebo + SDT Placebo Participants will receive SDT and matching placebo. SDT will be determined on a per participant basis. Placebo will be administered orally, once daily until completion of Part 1. (Part 2) Elenestinib Dose 1 + SDT Elenestinib Participants will receive SDT and elenestinib. SDT will be determined on a per participant basis. Elenestinib will be administered orally, once daily for approximately 48 weeks. (Part 2) Placebo + SDT Placebo Participants will receive SDT and matching placebo. SDT will be determined on a per participant basis. Placebo will be administered orally, once daily for approximately 48 weeks. (Part 3) Elenestinib + SDT Elenestinib Participants will receive SDT and elenestinib. SDT will be determined on a per participant basis. Elenestinib will be administered orally, once daily for up to approximately 5 years. (Part S) Elenestinib Dose 1 + SDT Elenestinib Participants will receive SDT and elenestinib. SDT will be determined on a per participant basis. Elenestinib will be administered orally, once daily for up to approximately 5 years. (Part K) Elenestinib Dose 1 + SDT Elenestinib Participants will receive SDT and elenestinib. SDT will be determined on a per participant basis. Elenestinib will be administered orally, once daily for up to approximately 5 years. (PK groups) Elenestinib + SDT Elenestinib Participants will receive SDT and elenestinib. SDT will be determined on a per participant basis. Elenestinib will be administered orally, once daily for up to approximately 5 years.
- Primary Outcome Measures
Name Time Method Part 1: Number of participants with Treatment-emergent Adverse Events (TEAEs) Up to 12 weeks Part 2: Mean change from baseline in ISM-SAF TSS Baseline, Week 49 Part 3: Number of participants with Adverse Events (AEs) Up to 5 years Part 3: Change from baseline in ISM-SAF TSS Baseline up to 5 years Part 1: Mean change from baseline in ISM-Symptom in Assessment Form (ISM-SAF) Total Symptom Score (TSS) Baseline, Week 13
- Secondary Outcome Measures
Name Time Method Part 1: Change from baseline in serum tryptase Baseline, Week 13 Part 1: Change from baseline in KIT D816V allele fraction in blood Baseline, Week 13 Part K: Mean change from baseline in ISM-SAF TSS Baseline up to 5 years Part K: Change from baseline in QoL scores Baseline up to 5 years Part 1: Change from baseline in Bone Marrow (BM) mast cells Baseline, Week 13 Part 1: Mean change from baseline in ISM-SAF individual symptom scores Baseline, Week 13 Part 1: Time to achieve 30% reduction from baseline in ISM-SAF TSS Baseline up to Week 13 Part 1: Time to achieve 30% reduction from baseline in ISM-SAF domain scores Baseline up to Week 13 Part 2: Proportion of participants achieving normalized tryptase Baseline up to Week 49 Part 2: Proportion of participants who achieve an undetectable level or at least a 50% reduction in KIT D816V Variant Allele Frequency (VAF) Baseline up to Week 49 Part 2: Proportion of participants achieving symptom control as defined by achieving mild symptoms Baseline up to Week 49 Part 2: Mean percent change from baseline in Bone Mineral Density (BMD) Baseline, Week 49 Part 2: Mean change from baseline in the annualized rate of anaphylaxis events Baseline, Weeks 25 to 48 Part 2: Mean change from baseline in Quality of Life (QoL) scores Baseline, Week 49 Part 2: Mean change from baseline in ISM-SAF domain scores Baseline, Week 49 Part 2: Number of participants with AEs Up to Week 49 Part 2: Proportion of participants with a 50% reduction in ISM-SAF TSS Baseline, Weeks 24 and 48 Part 2: Proportion of participants with a 50% reduction in ISM-SAF domain scores Baseline, Weeks 24 and 48 Part 2: Proportion of participants with a 30% reduction in ISM-SAF TSS Baseline, Weeks 24 and 48 Part 2: Proportion of participants with a 30% reduction in ISM-SAF domain scores Baseline, Weeks 24 and 48 Part 3: Proportion of participants achieving symptom control as defined by achieving mild symptoms Baseline up to 5 years Part 3: Change from baseline in ISM-SAF domain scores Baseline, up to 5 years Part 3: Proportion of participants achieving a normalized tryptase Baseline up to 5 years Part 3: Change from baseline in BMD Baseline up to 5 years Part 3: Change from baseline in the annualized rate of anaphylaxis events Baseline up to 5 years Parts 2 and 3: Change from baseline in serum tryptase Baseline up to 5 years Parts 2 and 3: Change from baseline in KIT D816V allele fraction in blood Baseline up to 5 years Parts 2 and 3: Change from baseline in Bone Marrow (BM) mast cells Baseline up to 5 years Parts 2 and 3: Proportion of participants achieving controlled disease Baseline up to 5 years Parts 2 and 3: Change from baseline in skin lesions as assessed by the fractional body surface area of the most affected skin area Baseline up to 5 years Parts 2 and 3: Change from baseline in the number of concomitant medications identified as SDT Baseline up to 5 years Parts 2 and 3: Change from baseline in ISM-SAF Individual Symptom Scores Baseline up to 5 years Parts 2 and 3: Change from baseline in ISM-SAF Lead (most severe) Symptom Score Baseline up to 5 years Parts 2 and 3: Change from baseline in QoL scores Baseline up to 5 years Part S: Number of participants with AEs Baseline up to 5 years Part S: Proportion of participants who achieve a Pure Pathologic Response (PPR) Baseline up to 5 years Part S: Mean change from baseline in ISM-SAF Baseline, Week 25 Part K: Number of participants with AEs Baseline up to 5 years Part K: Change from baseline in serum tryptase Baseline up to 5 years Part K: Change from baseline in KIT D816V allele fraction in blood Baseline up to 5 years
Related Research Topics
Explore scientific publications, clinical data analysis, treatment approaches, and expert-compiled information related to the mechanisms and outcomes of this trial. Click any topic for comprehensive research insights.
How does elenestinib (BLU-263) target KIT D816V mutations in indolent systemic mastocytosis compared to other KIT inhibitors?
What are the comparative efficacy outcomes of BLU-263 versus standard-of-care therapies for ISM in NCT04910685?
Which biomarkers predict response to BLU-263 in patients with KIT-mutant indolent systemic mastocytosis?
What are the most common adverse events associated with BLU-263 in mast cell disorders and management strategies?
How does BLU-263's mechanism differ from midostaurin in treating systemic mastocytosis subtypes?
Trial Locations
- Locations (52)
University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States
Stanford Cancer Institute
🇺🇸Palo Alto, California, United States
Brigham and Women's Hospital
🇺🇸Boston, Massachusetts, United States
Michigan Medicine University of Michigan
🇺🇸Ann Arbor, Michigan, United States
Mayo Clinic
🇺🇸Rochester, Minnesota, United States
Roswell Park Cancer Institute
🇺🇸Buffalo, New York, United States
Columbia University Medical Center
🇺🇸New York, New York, United States
University of Cincinnati Medical Center
🇺🇸Cincinnati, Ohio, United States
The University of Texas, MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
Huntsman Cancer Institute, University of Utah
🇺🇸Salt Lake City, Utah, United States
Scroll for more (42 remaining)University of Alabama at Birmingham🇺🇸Birmingham, Alabama, United States