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NCT04910685PHASE2, PHASE3Recruiting

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

Blueprint Medicines Corporation

Start Date

11/30/2021

Completion Date

9/30/2032

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.

Eligibility Criteria

Age Range: 18 years to No maximum

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.

Interventions

DRUG

Elenestinib

DRUG

Placebo

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Conditions

Indolent Systemic MastocytosisSmoldering Systemic Mastocytosis

Locations

University of Alabama at Birmingham

Birmingham, Alabama 35294

United States

David Geffen School of Medicine at UCLA

Los Angeles, California 90095

United States

Stanford Cancer Institute

Palo Alto, California 94305

United States

UCHealth Blood Disorders and Cell Therapies Center - Anschutz Medical Campus

Aurora, Colorado 80045

United States

Winship Cancer Institute, Emory University

Atlanta, Georgia 30322

United States

Brigham and Women's Hospital

Boston, Massachusetts 02115

United States

Michigan Medicine University of Michigan

Ann Arbor, Michigan 48109

United States

Mayo Clinic

Rochester, Minnesota 55902

United States

Roswell Park Cancer Institute

Buffalo, New York 14263

United States

Columbia University Medical Center

New York, New York 10032

United States

Duke Asthma, Allergy and Airway Center

Durham, North Carolina 27705

United States

University of Cincinnati Medical Center

Cincinnati, Ohio 45219

United States

The University of Texas, MD Anderson Cancer Center

Houston, Texas 77030

United States

Huntsman Cancer Institute, University of Utah

Salt Lake City, Utah 84112

United States

CHP Centro Hematologico Pavlovsky

Buenos Aires, 1113

Argentina

Consultorios Medicos Dr. Doreski - Fundacion Respirar

Buenos Aires, 1426

Argentina

Princess Alexandra Hospital

Woolloongabba, Queensland

Australia

The Alfred Hospital

Melbourne, Victoria 3004

Australia

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

Linz, 4021

Austria

Unitversitair Ziekenhuis Antwerpen

Edegem, Antwerpen

Belgium

Universitair Ziekenhuis Gent

Ghent, 9000

Belgium

CHU Tivoli

La Louvière, 7100

Belgium

Hospital das Clínicas da Faculdade de Medicina da USP - HCFMUSP

São Paulo, 05403-010

Brazil

Fakultní nemocnice Brno, Interní hematologická a onkologická klinika

Brno, 625 00

Czechia

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

Prague, 100 34

Czechia

CHU Amiens-Picardie

Amiens, 80000

France

CHU de Caen

Caen,

France

CHU Grenoble

Grenoble, 38043

France

CHU de Limoges

Limoges, 87042

France

CHU de Nantes

Nantes, 44093

France

Hôpital de la Pitié Salpétrière

Paris, 75013

France

Hôpital Necker - Départementd 'HématologieA dultes

Paris, 75015

France

CHU de Poitiers

Poitiers, 86000

France

CHU Toulouse - Hopital Larrey

Toulouse,

France

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

Aachen,

Germany

Charité - Universitätsmedizin Berlin Institute of Allergology

Berlin, 12203

Germany

University Clinic Erlangen

Erlangen, 91054

Germany

University Clinic Hamburg Eppendorf

Hamburg, 20246

Germany

Universitätsmedizin Mannheim III. Medizinische Klinik Universität Heidelberg Medizinische Fakultät Mannheim

Mannheim, 68167

Germany

LMU Klinikum

Munich, 80377

Germany

University General Hospital - General Hospital of West Attica

Chaïdári, 12462

Greece

General Hospital of Thessaloniki "G. Papanikolaou"

Thessaloniki, 57010

Greece

Cork University Hospital

Cork, T12 DC4A

Ireland

UOC Ematologia

Milan, Lombardy 20122

Italy

SOD Ematologia (Ambulatori)- AOUC Azienda Ospedaliero Universitaria Careggi

Florence, Tuscany 50134

Italy

Unita Operativa di Ematologia AOU Policlinico S. Orsola-Malpighi

Bologna, 40138

Italy

AOU Policlinico G.Rodolico - San Marco

Catania, 95123

Italy

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

Pavia, 27100

Italy

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

Salerno, 84131

Italy

Unità Operativa di Allergologia Azienda Ospedaliera Universitaria Integrata di Verona

Verona, 37126

Italy

ErasmusMC

Rotterdam, South Holland 3015 GD

Netherlands

University Medical Center Groningen

Groningen, 9713 GZ

Netherlands

Oslo University Hospital

Oslo, N-0424

Norway

Uniwersyteckie Centrum Kliniczne Klinika Alergologii

Gdansk, 80-214

Poland

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

Lisbon, 1169-050

Portugal

CHUPorto, EPE - Hospital de Santo António

Porto, 4099-001

Portugal

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

Porto, 4200-139

Portugal

Hospital Universitario Vall d'Hebron

Barcelona,

Spain

Hospital Universitario Ramon y Cajal

Madrid, 28034

Spain

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

Toledo, 45071

Spain

Uppsala University Hospital

Uppsala, 751 85

Sweden

University Hospital Basel

Basel, C-4031

Switzerland

Luzerner Kantonsspital

Lucerne, 6000

Switzerland

lstanbul Universitesi lstanbul Tip Fakultesi Hastanesi

Istanbul, 34093

Turkey (Türkiye)

Mersin VM Medikal Park Hastanesi

Mersin, 33200

Turkey (Türkiye)

University Hospital of Wales

Cardiff, Wales CF14 4XW

United Kingdom

University Hospital of Wales

Cardiff, CF14 4XW

United Kingdom

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

London, NW1 2PG

United Kingdom

Guy's and St Thomas's NHS Foundation Trust

London, SE1 7EH

United Kingdom

Cancer and Haematology Centre

Oxford, OX3 7LE

United Kingdom

University Hospital Plymouth NHS Trust

Plymouth, PL6 8DH

United Kingdom