Indolent Systemic MastocytosisPhase 2/3NCT04910685
(HARBOR) Study to Evaluate Efficacy and Safety of BLU-263 Versus Placebo in Patients With Indolent Systemic Mastocytosis
A Phase 2/3 study testing Elenestinib in people with Indolent Systemic Mastocytosis and Smoldering Systemic Mastocytosis, run by Blueprint Medicines Corporation at 88 sites in 25 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Indolent Systemic Mastocytosis, Smoldering Systemic Mastocytosis
- What is being tested?
- Elenestinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 534 participants
- Where
- 88 sitesin 25 countries
- Study dates
- 30 Nov 2021to 30 Sep 2032
- Phase
- Phase 2/3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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
Who cannot join
- 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.
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- 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.
Trial locations and contacts
88 sites in 25 countries. Contact the study team or a site near you to ask about taking part.
88 sites in 25 countries
United States15 sites, 15 recruiting
- Recruiting
Michigan Medicine University of Michigan
Ann Arbor, Michigan, 48109
- Recruiting
Winship Cancer Institute, Emory University
Atlanta, Georgia, 30322
- Recruiting
UCHealth Blood Disorders and Cell Therapies Center - Anschutz Medical Campus
Aurora, Colorado, 80045
- Recruiting
University of Alabama at Birmingham
Birmingham, Alabama, 35294
- Recruiting
Brigham and Women's Hospital
Boston, Massachusetts, 02115
- Recruiting
Roswell Park Cancer Institute
Buffalo, New York, 14263
- Recruiting
University of Cincinnati Medical Center
Cincinnati, Ohio, 45219
- Recruiting
Duke Asthma, Allergy and Airway Center
Durham, North Carolina, 27705
- Recruiting
The University of Texas, MD Anderson Cancer Center
Houston, Texas, 77030
- Recruiting
Orso Health, Modena Allergy and Asthma Inc
La Jolla, California, 92037
- Recruiting
David Geffen School of Medicine at UCLA
Los Angeles, California, 90095
- Recruiting
Columbia University Medical Center
New York, New York, 10032
- Recruiting
Stanford Cancer Institute
Palo Alto, California, 94305
- Recruiting
Mayo Clinic
Rochester, Minnesota, 55902
- Recruiting
Huntsman Cancer Institute, University of Utah
Salt Lake City, Utah, 84112
France9 sites, 9 recruiting
- Recruiting
CHU Amiens-Picardie
Amiens, 80000
- Recruiting
CHU de Caen
Caen
- Recruiting
CHU Grenoble
Grenoble, 38043
- Recruiting
CHU de Limoges
Limoges, 87042
- Recruiting
CHU de Nantes
Nantes, 44093
- Recruiting
Hôpital de la Pitié Salpétrière
Paris, 75013
- Recruiting
Hôpital Necker - Départementd 'HématologieA dultes
Paris, 75015
- Recruiting
CHU de Poitiers
Poitiers, 86000
- Recruiting
CHU Toulouse - Hopital Larrey
Toulouse
Italy9 sites, 9 recruiting
- Recruiting
Unita Operativa di Ematologia AOU Policlinico S. Orsola-Malpighi
Bologna, 40138
- Recruiting
AOU Policlinico G.Rodolico - San Marco
Catania, 95123
- Recruiting
SOD Ematologia (Ambulatori)- AOUC Azienda Ospedaliero Universitaria Careggi
Florence, Tuscany, 50134
- Recruiting
UOC Ematologia
Milan, Lombardy, 20122
- Recruiting
Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico
Milan, 20122
- Recruiting
S.C. Ematologia Fondazione I.R.C.C.S. Policlinico San Matteo
Pavia, 27100
- Recruiting
S.S.D. Immunologia Clinica e Allergologia Azienda Ospedaliera Universitaria San Giovanni di Dio e Ruggi d'Aragona
Salerno, 84131
- Recruiting
Unità Operativa di Allergologia Azienda Ospedaliera Universitaria Integrata di Verona
Verona, 37126
- Recruiting
Azienda Unita Locale Socia Sanitaria N8 Berica
Vicenza, 36100
Germany8 sites, 8 recruiting
- Recruiting
Universitätsklinikum RWTH Aachen Klinik für Hämatologie, Onkologie, Hämostaseologie und Stammzelltransplantation
Aachen
- Recruiting
Charité - Universitätsmedizin Berlin Institute of Allergology
Berlin, 12203
- Recruiting
University Clinic Erlangen
Erlangen, 91054
- Recruiting
University Clinic Hamburg Eppendorf
Hamburg, 20246
- Recruiting
Universitatsklinikum Schleswig-Holstein, Campus Lubeck
Lübeck, 23562
- Recruiting
Universitätsmedizin Mannheim III. Medizinische Klinik Universität Heidelberg Medizinische Fakultät Mannheim
Mannheim, 68167
- Recruiting
Klinikum rechts der Isar der Technischen Universitaet Muenchen
München, 81675
- Recruiting
LMU Klinikum
Munich, 80377
United Kingdom6 sites, 6 recruiting
- Recruiting
Queen Elizabeth Hospital, University Hospital Birmingham
Birmingham, B15 2GW
- Recruiting
University Hospital of Wales
Cardiff, Wales, CF14 4XW
- Recruiting
University College London Hospitals (UCLH), Haematology Cancer Clinical Trials Unit
London, NW1 2PG
- Recruiting
Guy's and St Thomas's NHS Foundation Trust
London, SE1 7EH
- Recruiting
GenesisCare
Oxford, OX4 6LB
- Recruiting
University Hospital Plymouth Trust - Derriford Hospital
Plymouth, PL6 8DH
Belgium4 sites, 4 recruiting
- Recruiting
Unitversitair Ziekenhuis Antwerpen
Edegem, Antwerpen
- Recruiting
Universitair Ziekenhuis Gent
Ghent, 9000
- Recruiting
CHU Tivoli
La Louvière, 7100
- Recruiting
UZ Leuven
Leuven, 3000
Portugal4 sites, 4 recruiting
- Recruiting
Centro Hospitalar de Lisboa Central, E.P.E. - Hospital de Santo Antonio dos Capuchos
Lisbon, 1169-050
- Recruiting
CHUPorto, EPE - Hospital de Santo António
Porto, 4099-001
- Recruiting
Centro Hospitalar Universitario Sao Joao, E.P.E.
Porto, 4200-139
- Recruiting
Unidade Local de Saude de Matosinhos, EPE - Hospital Pedro Hispanc
Senhora Da Hor, 4464-513
Australia3 sites, 3 recruiting
- Recruiting
The Canberra Hospital
Garran, ACT 2605
- Recruiting
The Alfred Hospital
Melbourne, Victoria, 3004
- Recruiting
Princess Alexandra Hospital
Woolloongabba, Queensland
Netherlands3 sites, 3 recruiting
- Recruiting
University Medical Center Groningen
Groningen, 9713 GZ
- Recruiting
Maastricht UMC+
Maastricht, 6229 HX
- Recruiting
ErasmusMC
Rotterdam, South Holland, 3015 GD
Spain3 sites, 3 recruiting
- Recruiting
Hospital Universitario Vall d'Hebron
Barcelona
- Recruiting
Hospital Universitario Ramon y Cajal
Madrid, 28034
- Recruiting
Hospital Virgen del Valle - Instituto de Estudios de Mastocitosis de Castilla-La Mancha
Toledo, 45071
Turkey (Türkiye)3 sites, 3 recruiting
- Recruiting
Ankara Universitesi Tip Fakultesi Cebeci Hastanesi
Ankara, 06620
- Recruiting
lstanbul Universitesi lstanbul Tip Fakultesi Hastanesi
Istanbul, 34093
- Recruiting
Mersin VM Medikal Park Hastanesi
Mersin, 33200
Argentina2 sites, 2 recruiting
- Recruiting
CHP Centro Hematologico Pavlovsky
Buenos Aires, 1113
- Recruiting
Consultorios Medicos Dr. Doreski - Fundacion Respirar
Buenos Aires, 1426
Czechia2 sites, 2 recruiting
- Recruiting
Fakultní nemocnice Brno, Interní hematologická a onkologická klinika
Brno, 625 00
- Recruiting
Fakultní nemocnice Královské Vinohrady, Hematologická klinika 3. LF UK v Praze a FNKV
Prague, 100 34
Greece2 sites, 2 recruiting
- Recruiting
University General Hospital - General Hospital of West Attica
Chaïdári, 12462
- Recruiting
General Hospital of Thessaloniki "G. Papanikolaou"
Thessaloniki, 57010
Poland2 sites, 2 recruiting
- Recruiting
Uniwersyteckie Centrum Kliniczne Klinika Alergologii
Gdansk, 80-214
- Recruiting
Samodzielny Publiczny Za kład Opieki Zdrowotnej Szpital Uniwersytecki w Krakowie
Krakow, 30-688
Romania2 sites, 2 recruiting
- Recruiting
Spitalul Clinic Colentina Bucuresti
Bucharest, 020125
- Recruiting
Spitalul Universitar De Urgenta Bucuresti
Bucharest, 050098
Sweden2 sites, 2 recruiting
- Recruiting
Karolinska Universitetssjukhuset Huddinge
Stockholm, 141 57
- Recruiting
Uppsala University Hospital
Uppsala, 751 85
Switzerland2 sites, 2 recruiting
- Recruiting
University Hospital Basel
Basel, C-4031
- Recruiting
Luzerner Kantonsspital
Lucerne, 6000
Austria1 site, 1 recruiting
- Recruiting
Kepler Universitatsklinikum, Med Campus III. Clinic of Internal Medicine 3 - Hematology and Oncology
Linz, 4021
Brazil1 site, 1 recruiting
- Recruiting
Hospital das Clínicas da Faculdade de Medicina da USP - HCFMUSP
São Paulo, 05403-010
Denmark1 site, 1 recruiting
- Recruiting
Odense University Hospital and University of Southern Denmark
Odense, 5000
About this study
Official title: 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.
- Being tested
- Elenestinib, Placebo
- Keywords
- ISM, SSM
- Medical subject headings
- Mastocytosis, Systemic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ElenestinibDrug
Also called BLU-263
Elenestinib oral tablet
PlaceboDrug
Placebo oral tablet
| Study group | Role | What they receive |
|---|---|---|
| (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. Receives: 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. Receives: 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. Receives: 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. Receives: 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. Receives: 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. Receives: 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. Receives: 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. Receives: 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. Receives: 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. Receives: Drug: Elenestinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Part 1: Number of participants with Treatment-emergent Adverse Events (TEAEs)
Measured: Up to 12 weeks
Part 1: Mean change from baseline in ISM-Symptom in Assessment Form (ISM-SAF) Total Symptom Score (TSS)
Measured: Baseline, Week 13
Part 2: Mean change from baseline in ISM-SAF TSS
Measured: Baseline, Week 49
Part 3: Number of participants with Adverse Events (AEs)
Measured: Up to 5 years
Part 3: Change from baseline in ISM-SAF TSS
Measured: Baseline up to 5 years
Secondary outcomes (40)
Part 1: Change from baseline in serum tryptase
Measured: Baseline, Week 13
Part 1: Change from baseline in KIT D816V allele fraction in blood
Measured: Baseline, Week 13
Part 1: Change from baseline in Bone Marrow (BM) mast cells
Measured: Baseline, Week 13
Part 1: Mean change from baseline in ISM-SAF individual symptom scores
Measured: Baseline, Week 13
Part 1: Time to achieve 30% reduction from baseline in ISM-SAF TSS
Measured: Baseline up to Week 13
Part 1: Time to achieve 30% reduction from baseline in ISM-SAF domain scores
Measured: Baseline up to Week 13
Part 2: Proportion of participants achieving normalized tryptase
Measured: 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)
Measured: Baseline up to Week 49
Part 2: Proportion of participants achieving symptom control as defined by achieving mild symptoms
Measured: Baseline up to Week 49
Part 2: Mean percent change from baseline in Bone Mineral Density (BMD)
Measured: Baseline, Week 49
Part 2: Mean change from baseline in the annualized rate of anaphylaxis events
Measured: Baseline, Weeks 25 to 48
Part 2: Mean change from baseline in Quality of Life (QoL) scores
Measured: Baseline, Week 49
Part 2: Mean change from baseline in ISM-SAF domain scores
Measured: Baseline, Week 49
Part 2: Number of participants with AEs
Measured: Up to Week 49
Part 2: Proportion of participants with a 50% reduction in ISM-SAF TSS
Measured: Baseline, Weeks 24 and 48
Part 2: Proportion of participants with a 50% reduction in ISM-SAF domain scores
Measured: Baseline, Weeks 24 and 48
Part 2: Proportion of participants with a 30% reduction in ISM-SAF TSS
Measured: Baseline, Weeks 24 and 48
Part 2: Proportion of participants with a 30% reduction in ISM-SAF domain scores
Measured: Baseline, Weeks 24 and 48
Part 3: Proportion of participants achieving symptom control as defined by achieving mild symptoms
Measured: Baseline up to 5 years
Part 3: Change from baseline in ISM-SAF domain scores
Measured: Baseline, up to 5 years
Part 3: Proportion of participants achieving a normalized tryptase
Measured: Baseline up to 5 years
Part 3: Change from baseline in BMD
Measured: Baseline up to 5 years
Part 3: Change from baseline in the annualized rate of anaphylaxis events
Measured: Baseline up to 5 years
Parts 2 and 3: Change from baseline in serum tryptase
Measured: Baseline up to 5 years
Parts 2 and 3: Change from baseline in KIT D816V allele fraction in blood
Measured: Baseline up to 5 years
Parts 2 and 3: Change from baseline in Bone Marrow (BM) mast cells
Measured: Baseline up to 5 years
Parts 2 and 3: Proportion of participants achieving controlled disease
Measured: 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
Measured: Baseline up to 5 years
Parts 2 and 3: Change from baseline in the number of concomitant medications identified as SDT
Measured: Baseline up to 5 years
Parts 2 and 3: Change from baseline in ISM-SAF Individual Symptom Scores
Measured: Baseline up to 5 years
Parts 2 and 3: Change from baseline in ISM-SAF Lead (most severe) Symptom Score
Measured: Baseline up to 5 years
Parts 2 and 3: Change from baseline in QoL scores
Measured: Baseline up to 5 years
Part S: Number of participants with AEs
Measured: Baseline up to 5 years
Part S: Proportion of participants who achieve a Pure Pathologic Response (PPR)
Measured: Baseline up to 5 years
Part S: Mean change from baseline in ISM-SAF
Measured: Baseline, Week 25
Part K: Number of participants with AEs
Measured: Baseline up to 5 years
Part K: Change from baseline in serum tryptase
Measured: Baseline up to 5 years
Part K: Change from baseline in KIT D816V allele fraction in blood
Measured: Baseline up to 5 years
Part K: Mean change from baseline in ISM-SAF TSS
Measured: Baseline up to 5 years
Part K: Change from baseline in QoL scores
Measured: Baseline up to 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Jun 2021
- Study start30 Nov 2021
- Primary completion30 Sep 2032 (estimated)
- Study completion30 Sep 2032 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Indolent Systemic MastocytosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Part 1 and Part 2: Randomized, Blinded Part 3, Part K, Part S and PK groups: Non-randomized, Open-label
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 534 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Blueprint Medicines Corporation
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04910685
- Sponsor's protocol ID
- BLU-263-1201
- Status last verified
- Oct 2026
- First submitted
- 17 May 2021
- Last updated
- 7 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 7 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Double-Blind, Placebo-Controlled Phase 2/3 Study of BLU-263 in Indolent Systemic Mastocytosis
- ClinicalTrials.gov ID
- NCT04910685
- Acronym / sponsor ID
- BLU-263-1201
- Keywords
- ISM, SSM
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 534 participants (estimated)
- Lead sponsor
- Blueprint Medicines CorporationIndustry (pharma, biotech, devices)
- Study start
- 30 Nov 2021 (actual)
- Primary completion
- 30 Sep 2032 (estimated)
- Study completion
- 30 Sep 2032 (estimated)
- First posted
- 2 Jun 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 10
- Model description
- Part 1 and Part 2: Randomized, Blinded Part 3, Part K, Part S and PK groups: Non-randomized, Open-label
| Arm | Type | Receives |
|---|---|---|
| (Part 1) Elenestinib Dose 1 + SDT | Experimental | Drug: ElenestinibParticipants 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 | Experimental | Drug: ElenestinibParticipants 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 | Experimental | Drug: ElenestinibParticipants 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 comparator | Drug: PlaceboParticipants 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 | Experimental | Drug: ElenestinibParticipants 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 comparator | Drug: PlaceboParticipants 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 | Experimental | Drug: ElenestinibParticipants 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 | Experimental | Drug: ElenestinibParticipants 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 | Experimental | Drug: ElenestinibParticipants 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 | Experimental | Drug: ElenestinibParticipants 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- -Participant must have an Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 to 2.
- 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.
Key exclusion criteria (9 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ElenestinibAlso: BLU-263Elenestinib oral tablet | Drug | (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 |
| PlaceboPlacebo oral tablet | Drug | (Part 1) Placebo + SDT, (Part 2) Placebo + SDT |
Primary outcome
Part 1: Number of participants with Treatment-emergent Adverse Events (TEAEs)
Time frame: Up to 12 weeks
Part 1: Mean change from baseline in ISM-Symptom in Assessment Form (ISM-SAF) Total Symptom Score (TSS)
Time frame: Baseline, Week 13
Part 2: Mean change from baseline in ISM-SAF TSS
Time frame: Baseline, Week 49
Part 3: Number of participants with Adverse Events (AEs)
Time frame: Up to 5 years
Part 3: Change from baseline in ISM-SAF TSS
Time frame: Baseline up to 5 years
40 secondary outcomes
Part 1: Change from baseline in serum tryptase
Time frame: Baseline, Week 13
Part 1: Change from baseline in KIT D816V allele fraction in blood
Time frame: Baseline, Week 13
Part 1: Change from baseline in Bone Marrow (BM) mast cells
Time frame: Baseline, Week 13
Part 1: Mean change from baseline in ISM-SAF individual symptom scores
Time frame: Baseline, Week 13
Part 1: Time to achieve 30% reduction from baseline in ISM-SAF TSS
Time frame: Baseline up to Week 13
Part 1: Time to achieve 30% reduction from baseline in ISM-SAF domain scores
Time frame: Baseline up to Week 13
Part 2: Proportion of participants achieving normalized tryptase
Time frame: 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)
Time frame: Baseline up to Week 49
Part 2: Proportion of participants achieving symptom control as defined by achieving mild symptoms
Time frame: Baseline up to Week 49
Part 2: Mean percent change from baseline in Bone Mineral Density (BMD)
Time frame: Baseline, Week 49
Part 2: Mean change from baseline in the annualized rate of anaphylaxis events
Time frame: Baseline, Weeks 25 to 48
Part 2: Mean change from baseline in Quality of Life (QoL) scores
Time frame: Baseline, Week 49
Part 2: Mean change from baseline in ISM-SAF domain scores
Time frame: Baseline, Week 49
Part 2: Number of participants with AEs
Time frame: Up to Week 49
Part 2: Proportion of participants with a 50% reduction in ISM-SAF TSS
Time frame: Baseline, Weeks 24 and 48
Part 2: Proportion of participants with a 50% reduction in ISM-SAF domain scores
Time frame: Baseline, Weeks 24 and 48
Part 2: Proportion of participants with a 30% reduction in ISM-SAF TSS
Time frame: Baseline, Weeks 24 and 48
Part 2: Proportion of participants with a 30% reduction in ISM-SAF domain scores
Time frame: Baseline, Weeks 24 and 48
Part 3: Proportion of participants achieving symptom control as defined by achieving mild symptoms
Time frame: Baseline up to 5 years
Part 3: Change from baseline in ISM-SAF domain scores
Time frame: Baseline, up to 5 years
Part 3: Proportion of participants achieving a normalized tryptase
Time frame: Baseline up to 5 years
Part 3: Change from baseline in BMD
Time frame: Baseline up to 5 years
Part 3: Change from baseline in the annualized rate of anaphylaxis events
Time frame: Baseline up to 5 years
Parts 2 and 3: Change from baseline in serum tryptase
Time frame: Baseline up to 5 years
Parts 2 and 3: Change from baseline in KIT D816V allele fraction in blood
Time frame: Baseline up to 5 years
Parts 2 and 3: Change from baseline in Bone Marrow (BM) mast cells
Time frame: Baseline up to 5 years
Parts 2 and 3: Proportion of participants achieving controlled disease
Time frame: 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
Time frame: Baseline up to 5 years
Parts 2 and 3: Change from baseline in the number of concomitant medications identified as SDT
Time frame: Baseline up to 5 years
Parts 2 and 3: Change from baseline in ISM-SAF Individual Symptom Scores
Time frame: Baseline up to 5 years
Parts 2 and 3: Change from baseline in ISM-SAF Lead (most severe) Symptom Score
Time frame: Baseline up to 5 years
Parts 2 and 3: Change from baseline in QoL scores
Time frame: Baseline up to 5 years
Part S: Number of participants with AEs
Time frame: Baseline up to 5 years
Part S: Proportion of participants who achieve a Pure Pathologic Response (PPR)
Time frame: Baseline up to 5 years
Part S: Mean change from baseline in ISM-SAF
Time frame: Baseline, Week 25
Part K: Number of participants with AEs
Time frame: Baseline up to 5 years
Part K: Change from baseline in serum tryptase
Time frame: Baseline up to 5 years
Part K: Change from baseline in KIT D816V allele fraction in blood
Time frame: Baseline up to 5 years
Part K: Mean change from baseline in ISM-SAF TSS
Time frame: Baseline up to 5 years
Part K: Change from baseline in QoL scores
Time frame: Baseline up to 5 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Oct 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
88 sites in 25 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Elenestinib in people with Indolent Systemic Mastocytosis and Smoldering Systemic Mastocytosis, run by Blueprint Medicines Corporation at 88 sites in 25 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 7 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 88 sites in United States, France, Italy, Germany, United Kingdom and 20 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Blueprint Medicines (617-714-6707, medinfo@blueprintmedicines.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Part 1: Number of participants with Treatment-emergent Adverse Events (TEAEs) (time frame: Up to 12 weeks). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Oct 2026.