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

NCT ID: NCT03580655

Last Updated: 2025-04-30

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

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

107 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-11-21

Study Completion Date

2024-12-18

Brief Summary

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This is an open-label, single arm, Phase 2 study evaluating the efficacy and safety of avapritinib (BLU-285) in patients with advanced systemic mastocytosis (AdvSM), including patients with aggressive SM (ASM), SM with associated hematologic neoplasm (SM-AHN), and mast cell leukemia (MCL)

Detailed Description

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Conditions

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Advanced Systemic Mastocytosis Aggressive Systemic Mastocytosis Systemic Mastocytosis With an Associated Hematologic Neoplasm Mast Cell Leukemia

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Avapritinib

Avapritinib will be administered as an immediate release tablet, orally, continuously, in 28-day cycles

Group Type EXPERIMENTAL

Avapritinib

Intervention Type DRUG

Avapritinib tablet

Interventions

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Avapritinib

Avapritinib 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 a diagnosis of aggressive systemic mastocytosis (ASM), systemic mastocytosis with an associated hematologic neoplasm (SM-AHN) or mast cell leukemia (MCL) based on World Health Organization diagnostic criteria. Before enrollment, the Study Steering Committee must confirm the diagnosis of AdvSM (based on Central Pathology Laboratory assessment of bone marrow).
2. Patient must have a serum tryptase ≥ 20 ng/mL.
3. Patient must have Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 to 3.

Exclusion Criteria

1. Patient has received prior treatment with avapritinib.
2. Patient has received any cytoreductive therapy (including midostaurin and other TKIs, hydroxyurea, azacitidine) or an investigational agent less than 14 days, and for cladribine, interferon alpha, pegylated interferon and any antibody therapy (eg, brentuximab vedotin) less than 28 days before obtaining screening BM biopsy for this study.
3. Patient has eosinophilia and known positivity for the FIP1L1 PGDFRA fusion, unless the patient has demonstrated relapse or PD on prior imatinib therapy. Patients with eosinophilia (\> 1.5 × 10\^9/L), who do not have a detectable KIT D816 mutation, must be tested for a PDGFRA fusion mutation by fluorescence in situ hybridization (FISH) or polymerase chain reaction (PCR).
4. Patient has history of another primary malignancy that has been diagnosed or required therapy within 3 years before the first dose of study drug. The following are exempt from the 3-year limit: completely resected basal cell and squamous cell skin cancer, curatively treated localized prostate cancer, and completely resected carcinoma in situ of any site.
5. Patient has a QT interval corrected using Fridericia's formula (QTcF) \> 480 msec.
6. Patient has a known risk or recent history (12 months before the first dose of study drug) of intracranial bleeding (eg, brain aneurysm, concomitant vitamin K antagonist use).
7. Platelet count \< 50,000/μL (within 4 weeks of the first dose of study drug) or receiving platelet transfusion(s).
8. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \>3 x the upper limit of normal (ULN); no restriction if due to suspected liver infiltration by mast cells.
9. Bilirubin \>1.5 × ULN; no restriction if due to suspected liver infiltration by mast cells or Gilbert's disease. (In the case of Gilbert's disease, a direct bilirubin \>2 × ULN would be an exclusion.)
10. Estimated glomerular filtration rate (eGFR) \< 30 mL/min/1.73m2 or creatinine \> 1.5 × ULN.
11. Patient has a primary brain malignancy or metastases to the brain.
12. Patient has a history of a seizure disorder (eg, epilepsy) or requirement for antiseizure medication.
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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Stanford Cancer Institute

Stanford, California, United States

Site Status

Rush University Medical Center

Chicago, Illinois, United States

Site Status

The University of Kansas Cancer Center

Westwood, Kansas, United States

Site Status

Dana Farber Cancer Institute

Boston, Massachusetts, United States

Site Status

University of Michigan

Ann Arbor, Michigan, United States

Site Status

Washington University School of Medicine

St Louis, Missouri, United States

Site Status

Roswell Park Comprehensive Cancer Center

Buffalo, New York, United States

Site Status

Herbert Irving Comprehensive Cancer Center

New York, New York, United States

Site Status

University of Pennsylvania, Abramson Cancer Center

Philadelphia, Pennsylvania, United States

Site Status

University of Texas, MD Anderson Cancer Center

Houston, Texas, United States

Site Status

Mays Cancer Center

San Antonio, Texas, United States

Site Status

Huntsman Cancer Institute

Salt Lake City, Utah, United States

Site Status

Medizinische Universität Wien, Universitätsklinik für Innere Medizin I, Klinische Abteilung für Hämatologie und Hämostaseologie

Vienna, , Austria

Site Status

St. Michael's Hospital

Toronto, Ontario, Canada

Site Status

Odense University Hospital, Department of Haematology

Odense, , Denmark

Site Status

Hôpital Necker-Enfants Malades

Paris, , France

Site Status

CHU Toulouse - Hôpital Larrey

Toulouse, , France

Site Status

Uniklinik RWTH Aachen, Klinik für Hämatologie, Onkologie, Hämostaseologie und Stammzelltranslplantation

Aachen, , Germany

Site Status

Universitätsklinikum Hamburg-Eppendorf, Zentrum für Onkologie

Hamburg, , Germany

Site Status

Universitätsklinikum Leipzig, Medizinische Klinik und Poliklinik I - Hämatologie und Zelltherapie, lnternistische Onkologie, Hämostaseologie

Leipzig, , Germany

Site Status

Universitätsmedizin Mannheim III. Medizinische Klinik

Mannheim, , Germany

Site Status

Klinik und Poliklinik für Innere Medizin III, Klinikum rechts der Isar der TU München

Munich, , Germany

Site Status

Azienda Ospedaliero-Universitaria Careggi, CRIMM - Centro di Ricerca ed Innovazione per le Malattie Mieloproliferative

Florence, , Italy

Site Status

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

Salerno, , Italy

Site Status

Centro Ricerche Cliniche di Verona - Azienda Ospedaliera Universitaria Integrata di Verona

Verona, , Italy

Site Status

University Medical Center Groningen (UMCG)

Groningen, , Netherlands

Site Status

Oslo University Hospital-Rikshospitalet, Hematology

Oslo, , Norway

Site Status

Uniwersyteckie Centrum Kliniczne, Klinika Hematologii i Transplantologii

Gdansk, , Poland

Site Status

Uniwersytecki Szpital Kliniczny im. Jana Mikulicza-Radeckiego we Wrocławiu, Klinice Hematologii, Nowotworów Krwi i Transplantacji Szpiku

Wroclaw, , Poland

Site Status

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

Toledo, , Spain

Site Status

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

Glasgow, , United Kingdom

Site Status

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

London, , United Kingdom

Site Status

Countries

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United States Austria Canada Denmark France Germany Italy Netherlands Norway Poland Spain United Kingdom

References

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Reiter A, Gotlib J, Alvarez-Twose I, Radia DH, Lubke J, Bobbili PJ, Wang A, Norregaard C, Dimitrijevic S, Sullivan E, Louie-Gao M, Schwaab J, Galinsky IA, Perkins C, Sperr WR, Sriskandarajah P, Chin A, Sendhil SR, Duh MS, Valent P, DeAngelo DJ. Efficacy of avapritinib versus best available therapy in the treatment of advanced systemic mastocytosis. Leukemia. 2022 Aug;36(8):2108-2120. doi: 10.1038/s41375-022-01615-z. Epub 2022 Jul 5.

Reference Type DERIVED
PMID: 35790816 (View on PubMed)

Reiter A, Schwaab J, DeAngelo DJ, Gotlib J, Deininger MW, Pettit KM, Alvarez-Twose I, Vannucchi AM, Panse J, Platzbecker U, Hermine O, Dybedal I, Lin HM, Rylova SN, Ehlert K, Dimitrijevic S, Radia DH. Efficacy and safety of avapritinib in previously treated patients with advanced systemic mastocytosis. Blood Adv. 2022 Nov 8;6(21):5750-5762. doi: 10.1182/bloodadvances.2022007539.

Reference Type DERIVED
PMID: 35640224 (View on PubMed)

Gotlib J, Reiter A, Radia DH, Deininger MW, George TI, Panse J, Vannucchi AM, Platzbecker U, Alvarez-Twose I, Mital A, Hermine O, Dybedal I, Hexner EO, Hicks LK, Span L, Mesa R, Bose P, Pettit KM, Heaney ML, Oh ST, Sen J, Lin HM, Mar BG, DeAngelo DJ. Efficacy and safety of avapritinib in advanced systemic mastocytosis: interim analysis of the phase 2 PATHFINDER trial. Nat Med. 2021 Dec;27(12):2192-2199. doi: 10.1038/s41591-021-01539-8. Epub 2021 Dec 6.

Reference Type DERIVED
PMID: 34873345 (View on PubMed)

Other Identifiers

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2017-004836-13

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

BLU-285-2202

Identifier Type: -

Identifier Source: org_study_id

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