(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
Indolent Systemic Mastocytosis
About this trial
This is an interventional treatment trial for Indolent Systemic Mastocytosis
Eligibility Criteria
Key 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.
Key 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.
Sites / Locations
- University of Alabama at Birmingham
- Mayo Clinic Hospital
- Stanford Cancer Institute
- Mayo Clinic Florida
- H. Lee Moffitt Cancer Center
- Winship Cancer Institute, Emory University
- Rush University Medical Center
- University of Kansas Hospital
- Brigham & Women's Hospital
- Dana Farber Cancer Institute
- Michigan Medicine, University of Michigan
- Mayo Clinic
- Washington University School of Medicine
- Herbert Irving Comprehensive Cancer Center
- Duke University Health System (DUHS)
- University Hospitals Cleveland Medical Center
- University of Texas, MD Anderson Cancer Center
- Huntsman Cancer Institute
- Virginia Commonwealth University Medical Center
- University Hospital Antwerp
- Tom Baker Cancer Centre
- University of Alberta Hospital
- St. Michael's Hospital
- Odense Universitetshospital, ORCA/Allergicentret, Hudafdeling I og Allergicenter
- Hôpital de la Timone, Service de dermatologie
- Hôpital Pitié-Salpêtrière, Service de Dermatologie
- CHU Toulouse Larrey, CEREMAST, Service de Dermatologie et Allergologie cutanée
- Uniklinik RWTH Aachen
- Charité Universitätsmedizin Berlin
- University Clinic Hamburg Eppendorf, University Cancer Center Hamburg (UCCH)
- Universitätsklinikum Schleswig-Holstein, Hämatologie/Onkologie
- Universitätsklinik Mainz, Universitäts-Hautklinik, Clinical Research Center
- Universitätsmedizin Mannheim, III. Medizinische Klinik
- Klinikum rechts der Isar, Technische Universität München
- A.O.U di Bologna - IRCCS, Istituto di Ematologia Lorenzo e Ariosto Seragnoli, Ematologia
- Fondazione IRCCS Ca' Granda Ospedale Maggiore Poloclinico, UOC Ematologia
- A.O. OO.RR. S.Giovanni di Dio e Ruggi d'Aragona, University of Salerno
- Azienda Ospedaliera Universitaria Integrata di Verona
- University Medical Center Groningen (UMCG)
- Erasmus Medical Center
- Oslo Universitetssykehus, Rikshospitalet, Department of Hematology
- Hospital Universitari Vall d'Hebron
- lnstituto de Estudios de Mastocitosis de Castilla la Mancha, Hospital Virgen del Valle - Complejo Hospitalario de Toledo
- Karolinska University Hospital, Hematologimottagningen R51
- Akademiska sjukhuset, Hematologmottagningen/101A
- University Hospital Basel
- NHS Greater Glasgow and Clyde, Beatson West of Scotland Cancer Centre
- Guy's and St Thomas' NHS Foundation Trust - Guy's Hospital
- Clatterbridge Cancer Centre NHS Foundation Trust
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Arm 7
Experimental
Experimental
Experimental
Placebo Comparator
Experimental
Placebo Comparator
Experimental
(Part 1) Avapritinib Dose 1 + BSC
(Part 1) Avapritinib Dose 2 + BSC
(Part 1) Avapritinib Dose 3 + BSC
(Part 1) Placebo + BSC
(Part 2) Avapritinib RP2D + BSC
(Part 2) Placebo + BSC
(Part 3) Avapritinib RP2D + BSC
Avapritinib will be administered orally in continuous 28-day cycles
Avapritinib will be administered orally in continuous 28-day cycles
Avapritinib will be administered orally in continuous 28-day cycles
Placebo will be administered orally in continuous 28-day cycles
Avapritinib will be administered orally in continuous 28-day cycles
Placebo will be administered orally in continuous 28-day cycles
Avapritinib will be administered orally in continuous 28-day cycles