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

NCT ID: NCT04910685

Last Updated: 2026-01-30

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2/PHASE3

Total Enrollment

534 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-11-30

Study Completion Date

2032-09-30

Brief Summary

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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

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Conditions

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Indolent Systemic Mastocytosis Smoldering Systemic Mastocytosis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Part 1 and Part 2: Randomized, Blinded Part 3, Part K, Part S and PK groups: Non-randomized, Open-label
Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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(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.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Placebo oral tablet

(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.

Group Type EXPERIMENTAL

Elenestinib

Intervention Type DRUG

Elenestinib oral tablet

(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.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Placebo oral tablet

(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.

Group Type EXPERIMENTAL

Elenestinib

Intervention Type DRUG

Elenestinib oral tablet

(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.

Group Type EXPERIMENTAL

Elenestinib

Intervention Type DRUG

Elenestinib oral tablet

(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.

Group Type EXPERIMENTAL

Elenestinib

Intervention Type DRUG

Elenestinib oral tablet

(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.

Group Type EXPERIMENTAL

Elenestinib

Intervention Type DRUG

Elenestinib oral tablet

(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.

Group Type EXPERIMENTAL

Elenestinib

Intervention Type DRUG

Elenestinib oral tablet

(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.

Group Type EXPERIMENTAL

Elenestinib

Intervention Type DRUG

Elenestinib oral tablet

(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.

Group Type EXPERIMENTAL

Elenestinib

Intervention Type DRUG

Elenestinib oral tablet

Interventions

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Elenestinib

Elenestinib oral tablet

Intervention Type DRUG

Placebo

Placebo oral tablet

Intervention Type DRUG

Other Intervention Names

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BLU-263

Eligibility Criteria

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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

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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Blueprint Medicines Corporation

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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University of Alabama at Birmingham

Birmingham, Alabama, United States

Site Status RECRUITING

Stanford Cancer Institute

Palo Alto, California, United States

Site Status RECRUITING

UCHealth Blood Disorders and Cell Therapies Center - Anschutz Medical Campus

Aurora, Colorado, United States

Site Status RECRUITING

Brigham and Women's Hospital

Boston, Massachusetts, United States

Site Status RECRUITING

Michigan Medicine University of Michigan

Ann Arbor, Michigan, United States

Site Status RECRUITING

Mayo Clinic

Rochester, Minnesota, United States

Site Status RECRUITING

Roswell Park Cancer Institute

Buffalo, New York, United States

Site Status RECRUITING

Columbia University Medical Center

New York, New York, United States

Site Status RECRUITING

University of Cincinnati Medical Center

Cincinnati, Ohio, United States

Site Status RECRUITING

The University of Texas, MD Anderson Cancer Center

Houston, Texas, United States

Site Status RECRUITING

Huntsman Cancer Institute, University of Utah

Salt Lake City, Utah, United States

Site Status RECRUITING

Princess Alexandra Hospital

Woolloongabba, Queensland, Australia

Site Status RECRUITING

The Alfred Hospital

Melbourne, Victoria, Australia

Site Status RECRUITING

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

Linz, , Austria

Site Status RECRUITING

Unitversitair Ziekenhuis Antwerpen

Edegem, Antwerpen, Belgium

Site Status RECRUITING

CHU Amiens-Picardie

Amiens, , France

Site Status RECRUITING

CHU de Caen

Caen, , France

Site Status RECRUITING

CHU Grenoble

Grenoble, , France

Site Status RECRUITING

CHU de Limoges

Limoges, , France

Site Status RECRUITING

CHU de Nantes

Nantes, , France

Site Status RECRUITING

Hôpital de la Pitié Salpétrière

Paris, , France

Site Status RECRUITING

Hôpital Necker - Départementd 'HématologieA dultes

Paris, , France

Site Status RECRUITING

CHU de Poitiers

Poitiers, , France

Site Status RECRUITING

CHU Toulouse - Hopital Larrey

Toulouse, , France

Site Status RECRUITING

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

Aachen, , Germany

Site Status RECRUITING

Charité - Universitätsmedizin Berlin Institute of Allergology

Berlin, , Germany

Site Status RECRUITING

University Clinic Erlangen

Erlangen, , Germany

Site Status RECRUITING

University Clinic Hamburg Eppendorf

Hamburg, , Germany

Site Status RECRUITING

Universitätsmedizin Mannheim III. Medizinische Klinik Universität Heidelberg Medizinische Fakultät Mannheim

Mannheim, , Germany

Site Status RECRUITING

LMU Klinikum

Munich, , Germany

Site Status RECRUITING

UOC Ematologia

Milan, Lombardy, Italy

Site Status RECRUITING

SOD Ematologia (Ambulatori)- AOUC Azienda Ospedaliero Universitaria Careggi

Florence, Tuscany, Italy

Site Status RECRUITING

Unita Operativa di Ematologia AOU Policlinico S. Orsola-Malpighi

Bologna, , Italy

Site Status RECRUITING

AOU Policlinico G.Rodolico - San Marco

Catania, , Italy

Site Status RECRUITING

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

Pavia, , Italy

Site Status RECRUITING

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

Salerno, , Italy

Site Status RECRUITING

Unità Operativa di Allergologia Azienda Ospedaliera Universitaria Integrata di Verona

Verona, , Italy

Site Status RECRUITING

ErasmusMC

Rotterdam, South Holland, Netherlands

Site Status RECRUITING

University Medical Center Groningen

Groningen, , Netherlands

Site Status RECRUITING

Oslo University Hospital

Oslo, , Norway

Site Status RECRUITING

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

Lisbon, , Portugal

Site Status RECRUITING

CHUPorto, EPE - Hospital de Santo António

Porto, , Portugal

Site Status RECRUITING

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

Porto, , Portugal

Site Status RECRUITING

Hospital Universitario Vall d'Hebron

Barcelona, , Spain

Site Status RECRUITING

Hospital Universitario Ramon y Cajal

Madrid, , Spain

Site Status RECRUITING

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

Toledo, , Spain

Site Status RECRUITING

Uppsala University Hospital

Uppsala, , Sweden

Site Status RECRUITING

University Hospital Basel

Basel, , Switzerland

Site Status RECRUITING

Luzerner Kantonsspital

Lucerne, , Switzerland

Site Status RECRUITING

University Hospital of Wales

Cardiff, Wales, United Kingdom

Site Status RECRUITING

University Hospital of Wales

Cardiff, , United Kingdom

Site Status RECRUITING

Guy's and St Thomas's NHS Foundation Trust

London, , United Kingdom

Site Status RECRUITING

Cancer and Haematology Centre

Oxford, , United Kingdom

Site Status RECRUITING

University Hospital Plymouth NHS Trust

Plymouth, , United Kingdom

Site Status RECRUITING

Countries

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United States Australia Austria Belgium France Germany Italy Netherlands Norway Portugal Spain Sweden Switzerland United Kingdom

Central Contacts

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Blueprint Medicines

Role: CONTACT

617-714-6707

Other Identifiers

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BLU-263-1201

Identifier Type: -

Identifier Source: org_study_id

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