(PIONEER) Study to Evaluate Efficacy and Safety of Avapritinib (BLU-285), A Selective KIT Mutation-targeted Tyrosine Kinase Inhibitor, Versus Placebo in Patients With Indolent Systemic Mastocytosis

NCT ID: NCT03731260

Last Updated: 2025-09-23

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

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE2

Total Enrollment

251 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-04-16

Study Completion Date

2027-06-23

Brief Summary

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This is a Phase 2, randomized, double-blind, placebo-controlled study comparing the efficacy and safety of avapritinib + best supportive care (BSC) with placebo + BSC in patients with indolent systemic mastocytosis (ISM) whose symptoms are not adequately controlled by BSC. The study will be conducted in 3 parts. All patients will receive treatment with avapritinib during Part 3 including those rolling over from the placebo group.

Detailed Description

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Conditions

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Indolent Systemic Mastocytosis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

In Part 1 of the study, patients will be randomly assigned to 1 of 3 doses of avapritinib or to placebo + BSC. Once the recommended phase 2 dose (RP2D) of avapritinib is identified in Part 1, patients in Part 2 will be randomly assigned to receive avapritinib at the RP2D + BSC or matching placebo + BSC. In Part 3, patients who have completed treatment in Part 1 or Part 2 of the study (including those initially randomized to placebo) may participate in a long-term open-label extension, receiving avapritinib at the RP2D + BSC.
Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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(Part 1) Avapritinib Dose 1 + BSC

Avapritinib will be administered orally in continuous 28-day cycles

Group Type EXPERIMENTAL

Avapritinib

Intervention Type DRUG

Avapritinib tablet

(Part 1) Avapritinib Dose 2 + BSC

Avapritinib will be administered orally in continuous 28-day cycles

Group Type EXPERIMENTAL

Avapritinib

Intervention Type DRUG

Avapritinib tablet

(Part 1) Avapritinib Dose 3 + BSC

Avapritinib will be administered orally in continuous 28-day cycles

Group Type EXPERIMENTAL

Avapritinib

Intervention Type DRUG

Avapritinib tablet

(Part 1) Placebo + BSC

Placebo will be administered orally in continuous 28-day cycles

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Placebo tablet

(Part 2) Avapritinib RP2D + BSC

Avapritinib will be administered orally in continuous 28-day cycles

Group Type EXPERIMENTAL

Avapritinib

Intervention Type DRUG

Avapritinib tablet

(Part 2) Placebo + BSC

Placebo will be administered orally in continuous 28-day cycles

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Placebo tablet

(Part 3) Avapritinib RP2D + BSC

Avapritinib will be administered orally in continuous 28-day cycles

Group Type EXPERIMENTAL

Avapritinib

Intervention Type DRUG

Avapritinib tablet

Interventions

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Avapritinib

Avapritinib tablet

Intervention Type DRUG

Placebo

Placebo tablet

Intervention Type DRUG

Other Intervention Names

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BLU-285

Eligibility Criteria

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Inclusion Criteria

* 1\. Patient must have SM, confirmed by Central Pathology Review of BM biopsy, and central review of B- and C-findings by WHO diagnostic criteria.
* 2\. Patient must have moderate-to-severe symptoms based on minimum mean total symptom score (TSS) of the ISM Symptom Assessment Form (ISM-SAF) over the 14-day eligibility screening period.
* 3\. Patient must have failed to achieve adequate symptom control for 1 or more Baseline symptoms.
* 4\. For patients receiving corticosteroids, the dose must be ≤ 20 mg/d prednisone or equivalent, and the dose must be stable for ≥ 14 days.
* 5\. Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 to 2.

Exclusion Criteria

* 1\. Patient has been diagnosed with any of the following WHO SM subclassifications: cutaneous mastocytosis only, smoldering SM, SM with associated hematologic neoplasm, aggressive SM, mast cell leukemia, or mast cell sarcoma.
* 2\. Patient must not have received prior treatment with avapritinib.
* 3\. Patient must not have had any cytoreductive therapy including but not limited to masitinib and midostaurin, or investigational agent for \< 14 days or 5 half-lives of the drug (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 14-day ISM-SAF eligibility TSS assessment.
* 4\. Patient must not have received radiotherapy or psoralen and ultraviolet A (PUVA) therapy \< 14 days before beginning the 14-day ISM-SAF eligibility TSS assessment.
* 5\. Patient must not have received any hematopoietic growth factor the preceding 14 days before beginning the 14-day ISM-SAF eligibility TSS assessment.
* 6\. Patient must not have a QT interval corrected using Fridericia's formula (QTcF) of \> 480 msec.
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

Mayo Clinic Hospital

Phoenix, Arizona, United States

Site Status

Stanford Cancer Institute

Stanford, California, United States

Site Status

Mayo Clinic Florida

Jacksonville, Florida, United States

Site Status

H. Lee Moffitt Cancer Center

Tampa, Florida, United States

Site Status

Winship Cancer Institute, Emory University

Atlanta, Georgia, United States

Site Status

Rush University Medical Center

Chicago, Illinois, United States

Site Status

University of Kansas Hospital

Kansas City, Kansas, United States

Site Status

Brigham & Women's Hospital

Boston, Massachusetts, United States

Site Status

Dana Farber Cancer Institute

Boston, Massachusetts, United States

Site Status

Michigan Medicine, University of Michigan

Ann Arbor, Michigan, United States

Site Status

Mayo Clinic

Rochester, Minnesota, United States

Site Status

Washington University School of Medicine

St Louis, Missouri, United States

Site Status

Herbert Irving Comprehensive Cancer Center

New York, New York, United States

Site Status

Duke University Health System (DUHS)

Durham, North Carolina, United States

Site Status

University Hospitals Cleveland Medical Center

Cleveland, Ohio, United States

Site Status

University of Texas, MD Anderson Cancer Center

Houston, Texas, United States

Site Status

Huntsman Cancer Institute

Salt Lake City, Utah, United States

Site Status

Virginia Commonwealth University Medical Center

Richmond, Virginia, United States

Site Status

University Hospital Antwerp

Edegem, , Belgium

Site Status

Tom Baker Cancer Centre

Calgary, Alberta, Canada

Site Status

University of Alberta Hospital

Edmonton, Alberta, Canada

Site Status

St. Michael's Hospital

Toronto, Ontario, Canada

Site Status

Odense Universitetshospital, ORCA/Allergicentret, Hudafdeling I og Allergicenter

Odense, , Denmark

Site Status

Hôpital de la Timone, Service de dermatologie

Marseille, , France

Site Status

Hôpital Pitié-Salpêtrière, Service de Dermatologie

Paris, , France

Site Status

CHU Toulouse Larrey, CEREMAST, Service de Dermatologie et Allergologie cutanée

Toulouse, , France

Site Status

Uniklinik RWTH Aachen

Aachen, , Germany

Site Status

Charité Universitätsmedizin Berlin

Berlin, , Germany

Site Status

University Clinic Hamburg Eppendorf, University Cancer Center Hamburg (UCCH)

Hamburg, , Germany

Site Status

Universitätsklinikum Schleswig-Holstein, Hämatologie/Onkologie

Lübeck, , Germany

Site Status

Universitätsklinik Mainz, Universitäts-Hautklinik, Clinical Research Center

Mainz, , Germany

Site Status

Universitätsmedizin Mannheim, III. Medizinische Klinik

Mannheim, , Germany

Site Status

Klinikum rechts der Isar, Technische Universität München

Munich, , Germany

Site Status

A.O.U di Bologna - IRCCS, Istituto di Ematologia Lorenzo e Ariosto Seragnoli, Ematologia

Bologna, , Italy

Site Status

Fondazione IRCCS Ca' Granda Ospedale Maggiore Poloclinico, UOC Ematologia

Milan, , Italy

Site Status

A.O. OO.RR. S.Giovanni di Dio e Ruggi d'Aragona, University of Salerno

Salerno, , Italy

Site Status

Azienda Ospedaliera Universitaria Integrata di Verona

Verona, , Italy

Site Status

University Medical Center Groningen (UMCG)

Groningen, , Netherlands

Site Status

Erasmus Medical Center

Rotterdam, , Netherlands

Site Status

Oslo Universitetssykehus, Rikshospitalet, Department of Hematology

Oslo, , Norway

Site Status

Hospital Universitari Vall d'Hebron

Barcelona, , Spain

Site Status

lnstituto de Estudios de Mastocitosis de Castilla la Mancha, Hospital Virgen del Valle - Complejo Hospitalario de Toledo

Toledo, , Spain

Site Status

Karolinska University Hospital, Hematologimottagningen R51

Stockholm, , Sweden

Site Status

Akademiska sjukhuset, Hematologmottagningen/101A

Uppsala, , Sweden

Site Status

University Hospital Basel

Basel, , Switzerland

Site Status

NHS Greater Glasgow and Clyde, Beatson West of Scotland Cancer Centre

Glasgow, , United Kingdom

Site Status

Guy's and St Thomas' NHS Foundation Trust - Guy's Hospital

London, , United Kingdom

Site Status

Clatterbridge Cancer Centre NHS Foundation Trust

Metropolitan Borough of Wirral, , United Kingdom

Site Status

Countries

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United States Belgium Canada Denmark France Germany Italy Netherlands Norway Spain Sweden Switzerland United Kingdom

References

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Gotlib J, Castells M, Elberink HO, Siebenhaar F, Hartmann K, Broesby-Olsen S, George TI, Panse J, Alvarez-Twose I, Radia DH, Tashi T, Bulai Livideanu C, Sabato V, Heaney M, Van Daele P, Cerquozzi S, Dybedal I, Reiter A, Pongdee T, Barete S, Ustun C, Schwartz L, Ward BR, Schafhausen P, Vadas P, Bose P, DeAngelo DJ, Rein L, Vachhani P, Triggiani M, Bonadonna P, Rafferty M, Butt NM, Oh ST, Wortmann F, Ungerstedt J, Guilarte M, Taparia M, Kuykendall AT, Arana Yi C, Ogbogu P, Gaudy-Marqueste C, Mattsson M, Shomali W, Giannetti MP, Bidollari I, Lin HM, Sulllivan E, Mar B, Scherber R, Roche M, Akin C, Maurer M. Avapritinib versus Placebo in Indolent Systemic Mastocytosis. NEJM Evid. 2023 Jun;2(6):EVIDoa2200339. doi: 10.1056/EVIDoa2200339. Epub 2023 May 23.

Reference Type DERIVED
PMID: 38320129 (View on PubMed)

Padilla B, Shields AL, Taylor F, Li X, Mcdonald J, Green T, Boral AL, Lin HM, Akin C, Siebenhaar F, Mar B. Psychometric evaluation of the Indolent Systemic Mastocytosis Symptom Assessment Form (ISM-SAF) in a phase 2 clinical study. Orphanet J Rare Dis. 2021 Oct 18;16(1):434. doi: 10.1186/s13023-021-02037-3.

Reference Type DERIVED
PMID: 34663404 (View on PubMed)

Other Identifiers

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2018-000588-99

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

BLU-285-2203

Identifier Type: -

Identifier Source: org_study_id

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