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

NCT04910685 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: BLU-263-1201
• Study Type: interventional
• Target: 534
• Locations: 17 countries
• Sites: 62

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.

Conditions

Smoldering Systemic Mastocytosis; Indolent Systemic Mastocytosis

Keywords

ISM; SSM

Outcome Measures

Primary Outcomes (5)

• 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 Outcomes (40)

• 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

Study Arms (10)

(Part 1) Elenestinib Dose 1 + SDT

EXPERIMENTAL

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

(Part 1) Elenestinib Dose 2 + SDT

EXPERIMENTAL

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

(Part 1) Elenestinib Dose 3 + SDT

EXPERIMENTAL

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

(Part 1) Placebo + SDT

PLACEBO COMPARATOR

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

(Part 2) Elenestinib Dose 1 + SDT

EXPERIMENTAL

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

(Part 2) Placebo + SDT

PLACEBO COMPARATOR

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

(Part 3) Elenestinib + SDT

EXPERIMENTAL

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

(Part S) Elenestinib Dose 1 + SDT

EXPERIMENTAL

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

(Part K) Elenestinib Dose 1 + SDT

EXPERIMENTAL

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

(PK groups) Elenestinib + SDT

EXPERIMENTAL

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

Interventions

Placebo DRUG

Placebo oral tablet

(Part 1) Placebo + SDT; (Part 2) Placebo + SDT

Elenestinib DRUG

Elenestinib oral tablet

Also known as: BLU-263

(PK groups) Elenestinib + SDT; (Part 1) Elenestinib Dose 1 + SDT; (Part 1) Elenestinib Dose 2 + SDT; (Part 1) Elenestinib Dose 3 + SDT; (Part 2) Elenestinib Dose 1 + SDT; (Part 3) Elenestinib + SDT; (Part K) Elenestinib Dose 1 + SDT; (Part S) Elenestinib Dose 1 + SDT

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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).
• 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.

Sponsors & Collaborators

• Blueprint Medicines Corporation: lead

Study Sites (64)

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

RECRUITING

David Geffen School of Medicine at UCLA

Los Angeles, California, 90095, United States

RECRUITING

Stanford Cancer Institute

Palo Alto, California, 94305, United States

RECRUITING

UCHealth Blood Disorders and Cell Therapies Center - Anschutz Medical Campus

Aurora, Colorado, 80045, United States

RECRUITING

Winship Cancer Institute, Emory University

Atlanta, Georgia, 30322, United States

RECRUITING

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

RECRUITING

Michigan Medicine University of Michigan

Ann Arbor, Michigan, 48109, United States

RECRUITING

Mayo Clinic

Rochester, Minnesota, 55902, United States

RECRUITING

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

RECRUITING

Columbia University Medical Center

New York, New York, 10032, United States

RECRUITING

Duke Asthma, Allergy and Airway Center

Durham, North Carolina, 27705, United States

RECRUITING

University of Cincinnati Medical Center

Cincinnati, Ohio, 45219, United States

RECRUITING

The University of Texas, MD Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Huntsman Cancer Institute, University of Utah

Salt Lake City, Utah, 84112, United States

RECRUITING

Consultorios Medicos Dr. Doreski - Fundacion Respirar

Buenos Aires, 1426, Argentina

RECRUITING

Princess Alexandra Hospital

Woolloongabba, Queensland, Australia

RECRUITING

The Alfred Hospital

Melbourne, Victoria, 3004, Australia

RECRUITING

Kepler Universitatsklinikum, Med Campus III. Clinic of Internal Medicine 3 - Hematology and Oncology

Linz, 4021, Austria

RECRUITING

Unitversitair Ziekenhuis Antwerpen

Edegem, Antwerpen, Belgium

RECRUITING

CHU Tivoli

La Louvière, 7100, Belgium

RECRUITING

Fakultní nemocnice Královské Vinohrady, Hematologická klinika 3. LF UK v Praze a FNKV

Prague, 100 34, Czechia

RECRUITING

CHU Amiens-Picardie

Amiens, 80000, France

RECRUITING

CHU de Caen

Caen, France

RECRUITING

CHU Grenoble

Grenoble, 38043, France

RECRUITING

CHU de Limoges

Limoges, 87042, France

RECRUITING

CHU de Nantes

Nantes, 44093, France

RECRUITING

Hôpital de la Pitié Salpétrière

Paris, 75013, France

RECRUITING

Hôpital Necker - Départementd 'HématologieA dultes

Paris, 75015, France

RECRUITING

CHU de Poitiers

Poitiers, 86000, France

RECRUITING

CHU Toulouse - Hopital Larrey

Toulouse, France

RECRUITING

Universitätsklinikum RWTH Aachen Klinik für Hämatologie, Onkologie, Hämostaseologie und Stammzelltransplantation

Aachen, Germany

RECRUITING

Charité - Universitätsmedizin Berlin Institute of Allergology

Berlin, 12203, Germany

RECRUITING

University Clinic Erlangen

Erlangen, 91054, Germany

RECRUITING

University Clinic Hamburg Eppendorf

Hamburg, 20246, Germany

RECRUITING

Universitätsmedizin Mannheim III. Medizinische Klinik Universität Heidelberg Medizinische Fakultät Mannheim

Mannheim, 68167, Germany

RECRUITING

LMU Klinikum

Munich, 80377, Germany

RECRUITING

University General Hospital - General Hospital of West Attica

Chaïdári, 12462, Greece

RECRUITING

General Hospital of Thessaloniki "G. Papanikolaou"

Thessaloniki, 57010, Greece

RECRUITING

UOC Ematologia

Milan, Lombardy, 20122, Italy

RECRUITING

SOD Ematologia (Ambulatori)- AOUC Azienda Ospedaliero Universitaria Careggi

Florence, Tuscany, 50134, Italy

RECRUITING

Unita Operativa di Ematologia AOU Policlinico S. Orsola-Malpighi

Bologna, 40138, Italy

RECRUITING

AOU Policlinico G.Rodolico - San Marco

Catania, 95123, Italy

RECRUITING

S.C. Ematologia Fondazione I.R.C.C.S. Policlinico San Matteo

Pavia, 27100, Italy

RECRUITING

S.S.D. Immunologia Clinica e Allergologia Azienda Ospedaliera Universitaria San Giovanni di Dio e Ruggi d'Aragona

Salerno, 84131, Italy

RECRUITING

Unità Operativa di Allergologia Azienda Ospedaliera Universitaria Integrata di Verona

Verona, 37126, Italy

RECRUITING

ErasmusMC

Rotterdam, South Holland, 3015 GD, Netherlands

RECRUITING

University Medical Center Groningen

Groningen, 9713 GZ, Netherlands

RECRUITING

Oslo University Hospital

Oslo, N-0424, Norway

RECRUITING

Uniwersyteckie Centrum Kliniczne Klinika Alergologii

Gdansk, 80-214, Poland

RECRUITING

Centro Hospitalar de Lisboa Central, E.P.E. - Hospital de Santo Antonio dos Capuchos

Lisbon, 1169-050, Portugal

RECRUITING

CHUPorto, EPE - Hospital de Santo António

Porto, 4099-001, Portugal

RECRUITING

Centro Hospitalar Universitario Sao Joao, E.P.E.

Porto, 4200-139, Portugal

RECRUITING

Hospital Universitario Vall d'Hebron

Barcelona, Spain

RECRUITING

Hospital Universitario Ramon y Cajal

Madrid, 28034, Spain

RECRUITING

Hospital Virgen del Valle - Instituto de Estudios de Mastocitosis de Castilla-La Mancha

Toledo, 45071, Spain

RECRUITING

Uppsala University Hospital

Uppsala, 751 85, Sweden

RECRUITING

University Hospital Basel

Basel, C-4031, Switzerland

RECRUITING

Luzerner Kantonsspital

Lucerne, 6000, Switzerland

RECRUITING

University Hospital of Wales

Cardiff, Wales, CF14 4XW, United Kingdom

RECRUITING

University Hospital of Wales

Cardiff, CF14 4XW, United Kingdom

RECRUITING

University College London Hospitals (UCLH), Haematology Cancer Clinical Trials Unit

London, NW1 2PG, United Kingdom

RECRUITING

Guy's and St Thomas's NHS Foundation Trust

London, SE1 7EH, United Kingdom

RECRUITING

Cancer and Haematology Centre

Oxford, OX3 7LE, United Kingdom

RECRUITING

University Hospital Plymouth NHS Trust

Plymouth, PL6 8DH, United Kingdom

RECRUITING

MeSH Terms

Conditions

Mastocytosis, Systemic

Condition Hierarchy (Ancestors)

Mastocytosis; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Mast Cell Activation Disorders; Immune System Diseases

Central Study Contacts

Blueprint Medicines

CONTACT

617-714-6707; medinfo@blueprintmedicines.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Part 1 and Part 2: Randomized, Blinded Part 3, Part K, Part S and PK groups: Non-randomized, Open-label

Study Record Dates

• First Submitted: May 17, 2021
• First Posted: June 2, 2021
• Study Start: November 30, 2021
• Primary Completion (Estimated): September 30, 2032
• Study Completion (Estimated): September 30, 2032
• Last Updated: April 20, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

BE (2); ES (3); CH (2); US (14); FR (9); SE (1); AU (1); GR (2); CZ (1); AR (1); NL (2); DE (6); IT (7); PL (1); PT (3); GB (6); NO (1)