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Clinical Trial Details — Status: Active, not recruiting

Administrative data

NCT number NCT03731260
Other study ID # BLU-285-2203
Secondary ID 2018-000588-99
Status Active, not recruiting
Phase Phase 2
First received
Last updated
Start date April 16, 2019
Est. completion date January 31, 2028

Study information

Verified date June 2023
Source Blueprint Medicines Corporation
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical 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. All patients will receive treatment with avapritinib during Part 3 including those rolling over from the placebo group.


Recruitment information / eligibility

Status Active, not recruiting
Enrollment 251
Est. completion date January 31, 2028
Est. primary completion date June 23, 2027
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility 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.

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
Avapritinib
Avapritinib tablet
Placebo
Placebo tablet

Locations

Country Name City State
Belgium University Hospital Antwerp Edegem
Canada Tom Baker Cancer Centre Calgary Alberta
Canada University of Alberta Hospital Edmonton Alberta
Canada St. Michael's Hospital Toronto Ontario
Denmark Odense Universitetshospital, ORCA/Allergicentret, Hudafdeling I og Allergicenter Odense
France Hôpital de la Timone, Service de dermatologie Marseille
France Hôpital Pitié-Salpêtrière, Service de Dermatologie Paris
France CHU Toulouse Larrey, CEREMAST, Service de Dermatologie et Allergologie cutanée Toulouse
Germany Uniklinik RWTH Aachen Aachen
Germany Charité Universitätsmedizin Berlin Berlin
Germany University Clinic Hamburg Eppendorf, University Cancer Center Hamburg (UCCH) Hamburg
Germany Universitätsklinikum Schleswig-Holstein, Hämatologie/Onkologie Lübeck
Germany Universitätsklinik Mainz, Universitäts-Hautklinik, Clinical Research Center Mainz
Germany Universitätsmedizin Mannheim, III. Medizinische Klinik Mannheim
Germany Klinikum rechts der Isar, Technische Universität München Munich
Italy A.O.U di Bologna - IRCCS, Istituto di Ematologia Lorenzo e Ariosto Seragnoli, Ematologia Bologna
Italy Fondazione IRCCS Ca' Granda Ospedale Maggiore Poloclinico, UOC Ematologia Milan
Italy A.O. OO.RR. S.Giovanni di Dio e Ruggi d'Aragona, University of Salerno Salerno
Italy Azienda Ospedaliera Universitaria Integrata di Verona Verona
Netherlands University Medical Center Groningen (UMCG) Groningen
Netherlands Erasmus Medical Center Rotterdam
Norway Oslo Universitetssykehus, Rikshospitalet, Department of Hematology Oslo
Spain Hospital Universitari Vall d'Hebron Barcelona
Spain lnstituto de Estudios de Mastocitosis de Castilla la Mancha, Hospital Virgen del Valle - Complejo Hospitalario de Toledo Toledo
Sweden Karolinska University Hospital, Hematologimottagningen R51 Stockholm
Sweden Akademiska sjukhuset, Hematologmottagningen/101A Uppsala
Switzerland University Hospital Basel Basel
United Kingdom NHS Greater Glasgow and Clyde, Beatson West of Scotland Cancer Centre Glasgow
United Kingdom Guy's and St Thomas' NHS Foundation Trust - Guy's Hospital London
United Kingdom Clatterbridge Cancer Centre NHS Foundation Trust Wirral
United States Michigan Medicine, University of Michigan Ann Arbor Michigan
United States Winship Cancer Institute, Emory University Atlanta Georgia
United States University of Alabama at Birmingham Birmingham Alabama
United States Brigham & Women's Hospital Boston Massachusetts
United States Dana Farber Cancer Institute Boston Massachusetts
United States Rush University Medical Center Chicago Illinois
United States University Hospitals Cleveland Medical Center Cleveland Ohio
United States Duke University Health System (DUHS) Durham North Carolina
United States University of Texas, MD Anderson Cancer Center Houston Texas
United States Mayo Clinic Florida Jacksonville Florida
United States University of Kansas Hospital Kansas City Kansas
United States Herbert Irving Comprehensive Cancer Center New York New York
United States Mayo Clinic Hospital Phoenix Arizona
United States Virginia Commonwealth University Medical Center Richmond Virginia
United States Mayo Clinic Rochester Minnesota
United States Washington University School of Medicine Saint Louis Missouri
United States Huntsman Cancer Institute Salt Lake City Utah
United States Stanford Cancer Institute Stanford California
United States H. Lee Moffitt Cancer Center Tampa Florida

Sponsors (1)

Lead Sponsor Collaborator
Blueprint Medicines Corporation

Countries where clinical trial is conducted

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

Outcome

Type Measure Description Time frame Safety issue
Primary Part 1: Recommended Phase 2 dose (RP2D) in patients with ISM 9 months
Primary 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) 6 months
Primary Part 3: Number of Participants with Adverse Events Up to 5 years
Secondary Part 2: Proportion of patients with a =50% reduction in serum tryptase 6 months
Secondary 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 6 months
Secondary Part 2: Proportion of patients with =50% reduction in ISM-SAF TSS 6 months
Secondary Part 2: Proportion of patients with =30% reduction in ISM-SAF TSS 6 months
Secondary Part 2: Proportion of patients with a =50% reduction in bone marrow mast cells or no aggregates for patients with aggregates at Baseline 6 months
Secondary Parts 1, 2, and 3: Change in serum tryptase Up to 5 years
Secondary Parts 1, 2, and 3: Change in KIT D816V allele burden in blood Up to 5 years
Secondary Parts 1, 2, and 3: Change in bone marrow mast cells Up to 5 years
Secondary Parts 1, 2, and 3: Change in best supportive care (BSC) concomitant medication usage Up to 5 years
Secondary Parts 1, 2, and 3: Change from Baseline in ISM-SAF Score Up to 5 years
Secondary Parts 1, 2, and 3: Change in Mastocytosis Quality of Life Questionnaire (MC-QoL) Up to 5 years
Secondary Parts 1, 2, and 3: Change in Patient's Global Impression of Symptom Severity (PGIS) Up to 5 years
Secondary Parts 1, 2, and 3: Change in 12-item Short Form Health Survey (SF-12) 0 - 100 points (higher value represents better symptom outcomes) Up to 5 years
Secondary Parts 1, 2, and 3: Change in Patients' Global Impression of Change (PGIC) 1 - 7 (higher value represents worse symptom outcomes) Up to 5 years
Secondary Parts 1, 2, and 3: Change in EuroQuol 5 Dimensions 5 Levels (EQ 5D-5L) 0 - 100 (higher value represents better symptom outcomes) Up to 5 years
Secondary Parts 1, 2, and 3: Safety of avapritinib as assessed by number of adverse events CTCAE version 5.0 Up to 5 years
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Active, not recruiting NCT01920204 - Midostaurin in Indolent Systemic Mastocytosis Phase 2