(HARBOR) Study to Evaluate Efficacy and Safety of BLU-263 Versus Placebo in Patients With Indolent Systemic Mastocytosis

A Randomized, Double-Blind, Placebo-Controlled Phase 2/3 Study of BLU-263 in Indolent Systemic Mastocytosis

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.

Study Overview

• Status: Recruiting
• Conditions: Indolent Systemic Mastocytosis; Smoldering Systemic Mastocytosis
• Intervention / Treatment: Drug: Placebo; Drug: Elenestinib

• Study Type: Interventional
• Enrollment (Estimated): 534
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Blueprint Medicines; Phone Number: 617-714-6707; Email: medinfo@blueprintmedicines.com

Study Locations

• Argentina
  • Buenos Aires, Argentina, 1426
    • Recruiting
    • Consultorios Medicos Dr. Doreski - Fundacion Respirar
  • Buenos Aires, Argentina, 1113
    • Recruiting
    • CHP Centro Hematologico Pavlovsky
• Australia
  • Queensland
    • Woolloongabba, Queensland, Australia
      • Recruiting
      • Princess Alexandra Hospital
      • Principal Investigator: Robert Bird, MD
  • Victoria
    • Melbourne, Victoria, Australia, 3004
      • Recruiting
      • The Alfred Hospital
      • Principal Investigator: Tse-Chieh Teh, MD
• Austria
  • Linz, Austria, 4021
    • Recruiting
    • Kepler Universitatsklinikum, Med Campus III. Clinic of Internal Medicine 3 - Hematology and Oncology
    • Principal Investigator: Clemens Schmitt, MD
• Belgium
  • Ghent, Belgium, 9000
    • Recruiting
    • Universitair Ziekenhuis Gent
  • La Louvière, Belgium, 7100
    • Recruiting
    • CHU Tivoli
  • Antwerpen
    • Edegem, Antwerpen, Belgium
      • Recruiting
      • Unitversitair Ziekenhuis Antwerpen
      • Principal Investigator: Vito Sabato, MD
• Czechia
  • Brno, Czechia, 625 00
    • Recruiting
    • Fakultní nemocnice Brno, Interní hematologická a onkologická klinika
  • Prague, Czechia, 100 34
    • Recruiting
    • Fakultní nemocnice Královské Vinohrady, Hematologická klinika 3. LF UK v Praze a FNKV
• France
  • Amiens, France, 80000
    • Recruiting
    • CHU Amiens-Picardie
    • Principal Investigator: Clement Gourguechon, MD
  • Caen, France
    • Recruiting
    • CHU de Caen
  • Grenoble, France, 38043
    • Recruiting
    • CHU Grenoble
  • Limoges, France, 87042
    • Recruiting
    • CHU de Limoges
  • Nantes, France, 44093
    • Recruiting
    • Chu de Nantes
    • Principal Investigator: Antoine NEEL, MD
  • Paris, France, 75013
    • Recruiting
    • Hôpital de la Pitiê Salpêtriêre
    • Principal Investigator: Stephanie Barate, MD
  • Paris, France, 75015
    • Recruiting
    • Hôpital Necker - Départementd 'HématologieA dultes
    • Principal Investigator: Olivier Hermine, MD
  • Poitiers, France, 86000
    • Recruiting
    • Chu de Poitiers
    • Principal Investigator: Ewa Wierzbicka - Hainaut, MD
  • Toulouse, France
    • Recruiting
    • CHU Toulouse - Hopital Larrey
    • Principal Investigator: Cristina Bulai-Livideanu, MD
• Germany
  • Aachen, Germany
    • Recruiting
    • Universitätsklinikum RWTH Aachen Klinik für Hämatologie, Onkologie, Hämostaseologie und Stammzelltransplantation
    • Principal Investigator: Jens Panse, MD
  • Berlin, Germany, 12203
    • Recruiting
    • Charité - Universitätsmedizin Berlin Institute of Allergology
    • Principal Investigator: Marcus Maurer, MD
  • Erlangen, Germany, 91054
    • Recruiting
    • University Clinic Erlangen
    • Principal Investigator: Nicola Wagner, MD
  • Hamburg, Germany, 20246
    • Recruiting
    • University Clinic Hamburg Eppendorf
    • Principal Investigator: Philippe Schafhausen, MD
  • Mannheim, Germany, 68167
    • Recruiting
    • Universitätsmedizin Mannheim III. Medizinische Klinik Universität Heidelberg Medizinische Fakultät Mannheim
    • Principal Investigator: Juliana Schwaab, MD
  • Munich, Germany, 80377
    • Recruiting
    • LMU Klinikum
    • Principal Investigator: Franziska Rueff, MD
• Greece
  • Chaïdári, Greece, 12462
    • Recruiting
    • University General Hospital - General Hospital of West Attica
  • Thessaloniki, Greece, 57010
    • Recruiting
    • General Hospital of Thessaloniki "G. Papanikolaou"
• Italy
  • Bologna, Italy, 40138
    • Recruiting
    • Unita Operativa di Ematologia AOU Policlinico S. Orsola-Malpighi
    • Principal Investigator: Cristina Papayannidis, MD, PhD
  • Catania, Italy, 95123
    • Recruiting
    • AOU Policlinico G.Rodolico - San Marco
  • Pavia, Italy, 27100
    • Recruiting
    • S.C. Ematologia Fondazione I.R.C.C.S. Policlinico San Matteo
    • Principal Investigator: Chiara Elena, MD
  • Salerno, Italy, 84131
    • Recruiting
    • S.S.D. Immunologia Clinica e Allergologia Azienda Ospedaliera Universitaria San Giovanni di Dio e Ruggi d'Aragona
    • Principal Investigator: Massimo Triggiani, MD
  • Verona, Italy, 37126
    • Recruiting
    • Unità Operativa di Allergologia Azienda Ospedaliera Universitaria Integrata di Verona
    • Principal Investigator: Patrizia Bonadonna, MD
  • Lombardy
    • Milan, Lombardy, Italy, 20122
      • Recruiting
      • UOC Ematologia
  • Tuscany
    • Florence, Tuscany, Italy, 50134
      • Recruiting
      • SOD Ematologia (Ambulatori)- AOUC Azienda Ospedaliero Universitaria Careggi
• Netherlands
  • Groningen, Netherlands, 9713 GZ
    • Recruiting
    • University Medical Center Groningen
    • Principal Investigator: Hanneke Oude Elberink, MD
  • South Holland
    • Rotterdam, South Holland, Netherlands, 3015 GD
      • Recruiting
      • ErasmusMC
• Norway
  • Oslo, Norway, N-0424
    • Recruiting
    • Oslo University Hospital
    • Principal Investigator: Ingunn Dybedal, MD, PhD
• Poland
  • Gdansk, Poland, 80-214
    • Recruiting
    • Uniwersyteckie Centrum Kliniczne Klinika Alergologii
• Portugal
  • Lisbon, Portugal, 1169-050
    • Recruiting
    • Centro Hospitalar de Lisboa Central, E.P.E. - Hospital de Santo Antonio dos Capuchos
    • Principal Investigator: Patrícia Ribeiro, MD
  • Porto, Portugal, 4099-001
    • Recruiting
    • CHUPorto, EPE - Hospital de Santo António
    • Principal Investigator: Renata Cabral, MD
  • Porto, Portugal, 4200-139
    • Recruiting
    • Centro Hospitalar Universitario Sao Joao, E.P.E.
    • Principal Investigator: Tiago Azenha Rama, MIM
• Spain
  • Barcelona, Spain
    • Recruiting
    • Hospital Universitario Vall d'Hebron
    • Principal Investigator: Mar Guilarte Clavero, MD
  • Madrid, Spain, 28034
    • Recruiting
    • Hospital Universitario Ramón y Cajal
    • Principal Investigator: David González de Olano, MD
  • Toledo, Spain, 45071
    • Recruiting
    • Hospital Virgen del Valle - Instituto de Estudios de Mastocitosis de Castilla-La Mancha
    • Principal Investigator: Ivan Alvarz-Twose, MD, PhD
• Sweden
  • Uppsala, Sweden, 751 85
    • Recruiting
    • Uppsala University Hospital
• Switzerland
  • Basel, Switzerland, C-4031
    • Recruiting
    • University Hospital Basel
    • Principal Investigator: Karin Hartmann, MD
  • Lucerne, Switzerland, 6000
    • Recruiting
    • Luzerner Kantonsspital
• Turkey (Türkiye)
  • Istanbul, Turkey (Türkiye), 34093
    • Recruiting
    • lstanbul Universitesi lstanbul Tip Fakultesi Hastanesi
• United Kingdom
  • Cardiff, United Kingdom, CF14 4XW
    • Recruiting
    • University Hospital of Wales
  • London, United Kingdom, SE1 7EH
    • Recruiting
    • Guy's and St Thomas's NHS Foundation Trust
  • London, United Kingdom, NW1 2PG
    • Recruiting
    • University College London Hospitals (UCLH), Haematology Cancer Clinical Trials Unit
  • Oxford, United Kingdom, OX3 7LE
    • Recruiting
    • Cancer and Haematology Centre
    • Principal Investigator: Bethan Psaila, MD, PhD
  • Plymouth, United Kingdom, PL6 8DH
    • Recruiting
    • University Hospital Plymouth NHS Trust
  • Wales
    • Cardiff, Wales, United Kingdom, CF14 4XW
      • Recruiting
      • University Hospital of Wales
      • Principal Investigator: Steven Knapper, MD
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • Recruiting
      • University of Alabama at Birmingham
      • Principal Investigator: Pankit Vachhani, MD
  • California
    • Los Angeles, California, United States, 90095
      • Recruiting
      • David Geffen School of Medicine at UCLA
    • Palo Alto, California, United States, 94305
      • Recruiting
      • Stanford Cancer Institute
      • Principal Investigator: William Shomali, MD
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Recruiting
      • UCHealth Blood Disorders and Cell Therapies Center - Anschutz Medical Campus
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Recruiting
      • Winship Cancer Institute, Emory University
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Recruiting
      • Brigham and Women's Hospital
      • Principal Investigator: Mariana Castells, MD
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • Recruiting
      • Michigan Medicine University of Michigan
      • Principal Investigator: Cem Akin, MD
  • Minnesota
    • Rochester, Minnesota, United States, 55902
      • Recruiting
      • Mayo Clinic
      • Principal Investigator: Thanai Pongdee, MD
  • New York
    • Buffalo, New York, United States, 14263
      • Recruiting
      • Roswell Park Cancer Institute
      • Principal Investigator: Elizabeth Griffiths, MD
    • New York, New York, United States, 10032
      • Recruiting
      • Columbia University Medical Center
      • Principal Investigator: Joseph Jurcic, MD
  • North Carolina
    • Durham, North Carolina, United States, 27705
      • Recruiting
      • Duke Asthma, Allergy and Airway Center
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • Recruiting
      • University of Cincinnati Medical Center
      • Principal Investigator: Johnathan Bernstein, MD
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • The University of Texas, MD Anderson Cancer Center
      • Principal Investigator: Prithviraj Bose, MD
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • Recruiting
      • Huntsman Cancer Institute, University of Utah
      • Principal Investigator: Tsewang Tashi, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Key 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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

10

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: (Part 1) Elenestinib Dose 1 + SDT; 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.	Drug: Elenestinib; Elenestinib oral tablet; Other Names: BLU-263
Experimental: (Part 1) Elenestinib Dose 2 + SDT; 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.	Drug: Elenestinib; Elenestinib oral tablet; Other Names: BLU-263
Experimental: (Part 1) Elenestinib Dose 3 + SDT; 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.	Drug: Elenestinib; Elenestinib oral tablet; Other Names: BLU-263
Placebo Comparator: (Part 1) Placebo + SDT; 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.	Drug: Placebo; Placebo oral tablet
Experimental: (Part 2) Elenestinib Dose 1 + SDT; 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.	Drug: Elenestinib; Elenestinib oral tablet; Other Names: BLU-263
Placebo Comparator: (Part 2) Placebo + SDT; 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.	Drug: Placebo; Placebo oral tablet
Experimental: (Part 3) Elenestinib + SDT; 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.	Drug: Elenestinib; Elenestinib oral tablet; Other Names: BLU-263
Experimental: (Part S) Elenestinib Dose 1 + SDT; 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.	Drug: Elenestinib; Elenestinib oral tablet; Other Names: BLU-263
Experimental: (Part K) Elenestinib Dose 1 + SDT; 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.	Drug: Elenestinib; Elenestinib oral tablet; Other Names: BLU-263
Experimental: (PK groups) Elenestinib + SDT; 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.	Drug: Elenestinib; Elenestinib oral tablet; Other Names: BLU-263

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Part 1: Number of participants with Treatment-emergent Adverse Events (TEAEs)	Up to 12 weeks
Part 1: Mean change from baseline in ISM-Symptom in Assessment Form (ISM-SAF) Total Symptom Score (TSS)	Baseline, Week 13
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

Secondary Outcome Measures

Outcome Measure	Time Frame
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 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
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

Other Outcome Measures

Outcome Measure	Time Frame
Part M: the proportion of patient who achieve at least a 30% reduction in Mast Cell Quality of Life (MC-QoL) score	6 months

Collaborators and Investigators

• Sponsor: Blueprint Medicines Corporation

Study record dates

Study Major Dates

• Study Start (Actual): November 30, 2021
• Primary Completion (Estimated): September 30, 2032
• Study Completion (Estimated): September 30, 2032

Study Registration Dates

• First Submitted: May 17, 2021
• First Submitted That Met QC Criteria: May 27, 2021
• First Posted (Actual): June 2, 2021

Study Record Updates

• Last Update Posted (Actual): May 22, 2026
• Last Update Submitted That Met QC Criteria: May 19, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: ISM; SSM
• Additional Relevant MeSH Terms: Mast Cell Activation Disorders; Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms, Connective and Soft Tissue; Neoplasms, Connective Tissue; Mastocytosis; Mastocytosis, Systemic
• Other Study ID Numbers: BLU-263-1201

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No