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Indolent Systemic MastocytosisPhase 2NCT03731260

(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

A Phase 2 study testing Avapritinib in people with Indolent Systemic Mastocytosis, run by Blueprint Medicines Corporation at 49 sites in 13 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Indolent Systemic Mastocytosis
What is being tested?
Avapritinib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
251 participants
Where
49 sitesin 13 countries
Study dates
16 Apr 2019to 23 Jun 2027
Phase
Phase 2
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

  • 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.

Who cannot join

  • 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.

Trial locations and contacts

49 sites in 13 countries.

49 sites in 13 countries

United States19 sites

  • Michigan Medicine, University of Michigan

    Ann Arbor, Michigan, 48106

  • Winship Cancer Institute, Emory University

    Atlanta, Georgia, 30322

  • University of Alabama at Birmingham

    Birmingham, Alabama, 35294

  • Brigham & Women's Hospital

    Boston, Massachusetts, 02115

  • Dana Farber Cancer Institute

    Boston, Massachusetts, 02215

  • Rush University Medical Center

    Chicago, Illinois, 60612

  • University Hospitals Cleveland Medical Center

    Cleveland, Ohio, 44106

  • Duke University Health System (DUHS)

    Durham, North Carolina, 27710

  • University of Texas, MD Anderson Cancer Center

    Houston, Texas, 77030

  • Mayo Clinic Florida

    Jacksonville, Florida, 32224

  • University of Kansas Hospital

    Kansas City, Kansas, 66160

  • Herbert Irving Comprehensive Cancer Center

    New York, New York, 10032

  • Mayo Clinic Hospital

    Phoenix, Arizona, 85054

  • Virginia Commonwealth University Medical Center

    Richmond, Virginia, 23298

  • Mayo Clinic

    Rochester, Minnesota, 55905

  • Huntsman Cancer Institute

    Salt Lake City, Utah, 84112

  • Washington University School of Medicine

    St Louis, Missouri, 63110

  • Stanford Cancer Institute

    Stanford, California, 94305

  • H. Lee Moffitt Cancer Center

    Tampa, Florida, 33612

Other trials in United States

Germany7 sites

  • Uniklinik RWTH Aachen

    Aachen, 52074

  • Charité Universitätsmedizin Berlin

    Berlin, 10117

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

    Hamburg, 20246

  • Universitätsklinikum Schleswig-Holstein, Hämatologie/Onkologie

    Lübeck, 23538

  • Universitätsklinik Mainz, Universitäts-Hautklinik, Clinical Research Center

    Mainz, 55131

  • Universitätsmedizin Mannheim, III. Medizinische Klinik

    Mannheim, 68167

  • Klinikum rechts der Isar, Technische Universität München

    Munich, 80802

Other trials in Germany

Italy4 sites

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

    Bologna, 40138

  • Fondazione IRCCS Ca' Granda Ospedale Maggiore Poloclinico, UOC Ematologia

    Milan, 20122

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

    Salerno, 84131

  • Azienda Ospedaliera Universitaria Integrata di Verona

    Verona, 37126

Other trials in Italy

Canada3 sites

  • Tom Baker Cancer Centre

    Calgary, Alberta, T2N 4N2

  • University of Alberta Hospital

    Edmonton, Alberta, T6G 2B7

  • St. Michael's Hospital

    Toronto, Ontario, M5B 1W8

Other trials in Canada

France3 sites

  • Hôpital de la Timone, Service de dermatologie

    Marseille, 13385

  • Hôpital Pitié-Salpêtrière, Service de Dermatologie

    Paris, 75013

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

    Toulouse, 31059

Other trials in France

United Kingdom3 sites

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

    Glasgow, G12 OXL

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

    London, SE1 9RT

  • Clatterbridge Cancer Centre NHS Foundation Trust

    Metropolitan Borough of Wirral, CH63 4JY

Other trials in United Kingdom

Netherlands2 sites

  • University Medical Center Groningen (UMCG)

    Groningen, 9713 GZ

  • Erasmus Medical Center

    Rotterdam, 3015 GD

Other trials in Netherlands

Spain2 sites

  • Hospital Universitari Vall d'Hebron

    Barcelona, 08035

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

    Toledo, 45071

Other trials in Spain

Sweden2 sites

  • Karolinska University Hospital, Hematologimottagningen R51

    Stockholm, 141 86

  • Akademiska sjukhuset, Hematologmottagningen/101A

    Uppsala, 751 85

Other trials in Sweden

Belgium1 site

  • University Hospital Antwerp

    Edegem, 2650

Other trials in Belgium

Denmark1 site

  • Odense Universitetshospital, ORCA/Allergicentret, Hudafdeling I og Allergicenter

    Odense, DK-5000

Other trials in Denmark

Norway1 site

  • Oslo Universitetssykehus, Rikshospitalet, Department of Hematology

    Oslo, 0372

Other trials in Norway

Switzerland1 site

  • University Hospital Basel

    Basel, 4031

Other trials in Switzerland

About this study

Official title: A 3-Part, Randomized, Double-Blind, Placebo-Controlled Phase 2 Study to Evaluate Safety and Efficacy of Avapritinib (BLU-285), a Selective KIT Mutation-Targeted Tyrosine Kinase Inhibitor, in Indolent and Smoldering Systemic Mastocytosis With Symptoms Inadequately Controlled With Standard Therapy

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.

Being tested
Avapritinib, Placebo
Medical subject headings
Mastocytosis, Systemic

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AvapritinibDrug

    Also called BLU-285

    Avapritinib tablet

  • PlaceboDrug

    Placebo tablet

Study groups in NCT03731260
Study groupRoleWhat they receive
(Part 1) Avapritinib Dose 1 + BSCExperimentalAvapritinib will be administered orally in continuous 28-day cycles
Receives: Drug: Avapritinib
(Part 1) Avapritinib Dose 2 + BSCExperimentalAvapritinib will be administered orally in continuous 28-day cycles
Receives: Drug: Avapritinib
(Part 1) Avapritinib Dose 3 + BSCExperimentalAvapritinib will be administered orally in continuous 28-day cycles
Receives: Drug: Avapritinib
(Part 1) Placebo + BSCPlacebo comparatorPlacebo will be administered orally in continuous 28-day cycles
Receives: Drug: Placebo
(Part 2) Avapritinib RP2D + BSCExperimentalAvapritinib will be administered orally in continuous 28-day cycles
Receives: Drug: Avapritinib
(Part 2) Placebo + BSCPlacebo comparatorPlacebo will be administered orally in continuous 28-day cycles
Receives: Drug: Placebo
(Part 3) Avapritinib RP2D + BSCExperimentalAvapritinib will be administered orally in continuous 28-day cycles
Receives: Drug: Avapritinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Part 1: Recommended Phase 2 dose (RP2D) in patients with ISM

    Measured: 9 months

  2. Part 2: Mean change in ISM Symptom Assessment Form (ISM-SAF) total symptom score (TSS) as compared to placebo

    0 - 110 points (higher value represents worse symptom outcomes)

    Measured: 6 months

  3. Part 3: Number of Participants with Adverse Events

    Measured: Up to 5 years

Secondary outcomes (16)

  1. Part 2: Proportion of patients with a ≥50% reduction in serum tryptase

    Measured: 6 months

  2. Part 2: Proportion of patients with a ≥50% reduction in peripheral blood V-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog aspartate 816 valine (KIT D816V) allele fraction or undetectable for patients with detectable mutation at Baseline

    Measured: 6 months

  3. Part 2: Proportion of patients with ≥50% reduction in ISM-SAF TSS

    Measured: 6 months

  4. Part 2: Proportion of patients with ≥30% reduction in ISM-SAF TSS

    Measured: 6 months

  5. Part 2: Proportion of patients with a ≥50% reduction in bone marrow mast cells or no aggregates for patients with aggregates at Baseline

    Measured: 6 months

  6. Parts 1, 2, and 3: Change in serum tryptase

    Measured: Up to 5 years

  7. Parts 1, 2, and 3: Change in KIT D816V allele burden in blood

    Measured: Up to 5 years

  8. Parts 1, 2, and 3: Change in bone marrow mast cells

    Measured: Up to 5 years

  9. Parts 1, 2, and 3: Change in best supportive care (BSC) concomitant medication usage

    Measured: Up to 5 years

  10. Parts 1, 2, and 3: Change from Baseline in ISM-SAF Score

    Measured: Up to 5 years

  11. Parts 1, 2, and 3: Change in Mastocytosis Quality of Life Questionnaire (MC-QoL)

    Measured: Up to 5 years

  12. Parts 1, 2, and 3: Change in Patient's Global Impression of Symptom Severity (PGIS)

    Measured: Up to 5 years

  13. Parts 1, 2, and 3: Change in 12-item Short Form Health Survey (SF-12)

    0 - 100 points (higher value represents better symptom outcomes)

    Measured: Up to 5 years

  14. Parts 1, 2, and 3: Change in Patients' Global Impression of Change (PGIC)

    1 - 7 (higher value represents worse symptom outcomes)

    Measured: Up to 5 years

  15. Parts 1, 2, and 3: Change in EuroQuol 5 Dimensions 5 Levels (EQ 5D-5L)

    0 - 100 (higher value represents better symptom outcomes)

    Measured: Up to 5 years

  16. Parts 1, 2, and 3: Safety of avapritinib as assessed by number of adverse events

    CTCAE version 5.0

    Measured: 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.

  1. First posted6 Nov 2018
  2. Study start16 Apr 2019
  3. Primary completion23 Jun 2027 (estimated)
  4. Study completion23 Jun 2027 (estimated)

Resources

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
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
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.
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
251 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03731260
Sponsor's protocol ID
BLU-285-2203
Other IDs
2018-000588-99, 2018
Status last verified
Sep 2026
First submitted
30 Oct 2018
Last updated
2 Oct 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Siebenhaar F, Broesby-Olsen S, Castells M, George TI, Livideanu CB, Alvarez-Twose I, Panse J, Barete S, Reiter A, Dybedal I, Akin C, Van Daele P, Radia DH, Cerquozzi S, Ustun C, Sabato V, Gotlib J, Rafferty M, DeAngelo DJ, Schafhausen P, Ungerstedt J, Ogbogu PU, Florell S, Wada DA, Rets A, Lin HM, Bidollari I, Hong J, Shaheen D, Lampson B, Hartmann K. Avapritinib improves cutaneous involvement in patients with indolent systemic mastocytosis: Results from the randomized, phase 2, interventional PIONEER study. J Am Acad Dermatol. 2026 Jun;94(6):1705-1713. doi: 10.1016/j.jaad.2026.02.025. Epub 2026 Feb 12.

    PubMed 41690487

  • Worth S, George TI, Shaheen DJ, Roche M, Vachhani P. Chronic Anaphylaxis With Indolent Systemic Mastocytosis: A Case Report. Case Rep Hematol. 2025 Nov 6;2025:9562195. doi: 10.1155/crh/9562195. eCollection 2025.

    PubMed 41244098

  • 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.

    PubMed 38320129

  • 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.

    PubMed 34663404

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Avapritinib in people with Indolent Systemic Mastocytosis, run by Blueprint Medicines Corporation at 49 sites in 13 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 5 inclusion and 6 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: under way, not looking for participants, as of the sponsor's last update on 2 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 49 sites in United States, Germany, Italy, Canada, France and 8 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 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.

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?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Part 1: Recommended Phase 2 dose (RP2D) in patients with ISM (time frame: 9 months). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03731260, which also lists 4 linked publications.

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 2 Oct 2026.

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