Indolent Systemic Mastocytosis Clinical Trial
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
Verified date | June 2023 |
Source | Blueprint Medicines Corporation |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
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.
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. |
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 |
Lead Sponsor | Collaborator |
---|---|
Blueprint Medicines Corporation |
United States, Belgium, Canada, Denmark, France, Germany, Italy, Netherlands, Norway, Spain, Sweden, Switzerland, United Kingdom,
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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