(Summit) a Study to Evaluate the Efficacy and Safety of CGT9486 Versus Placebo in Patients with Indolent or Smoldering Systemic Mastocytosis
- Conditions
- SSMMastocytosis, IndolentMastocytosis, SystemicMastocytosisISMBMMSmoldering Systemic MastocytosisBone Marrow Mastocytosis
- Interventions
- Registration Number
- NCT05186753
- Lead Sponsor
- Cogent Biosciences, Inc.
- Brief Summary
This is a multi-part, randomized, double-blind, placebo-controlled Phase 2 clinical study comparing the safety and efficacy of bezuclastinib (CGT9486) plus best supportive care (BSC) with placebo plus BSC in patients with nonadvanced systemic mastocytosis (NonAdvSM), including indolent systemic mastocytosis and smoldering systemic mastocytosis, whose symptoms are not adequately controlled by BSC. This study will be conducted in three parts. Patients in Parts 1a, 1b and 2 will receive bezuclastinib or placebo, and may roll over onto Part 3 to receive treatment with bezuclastinib.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 207
-
Diagnosed with 1 of the following diagnoses according to the 2016 World Health Organization (WHO) classification for systemic mastocytosis (SM):
- Indolent systemic mastocytosis (ISM),
- Bone marrow mastocytosis (BMM)
- Smoldering systemic mastocytosis (SSM)
-
Moderate-to-severe symptoms based on a minimum total symptom scoew (TSS) of the Mastocytosis Activity Score (MAS) and after establishing a stable regimen of at least 2 antimediator therapies over a 14-day eligibility period
-
Eastern Cooperative Oncology Group (ECOG) Performance Status 0 to 2
-
For patients receiving corticosteroids, the dose must be ≤10 mg/day of prednisone or equivalent
Key
- Persistent toxicity from previous therapy for NonAdvSM that has not resolved to ≤ Grade 1
- Diagnosed with any of the following WHO SM classifications: bone marrow mastocytosis, advanced systemic mastocytosis including SM with associated hematologic neoplasm, aggressive SM, mast cell leukemia; or mast cell sarcoma
- Diagnosed with mastocytosis of the skin without systemic involvement
- Received prior treatment with any targeted KIT inhibitor with the exception of approved agents for the treatment of SM
- Received prior cytoreductive therapy or investigational agent for <14 days or 5 half- lives of the drug and for cladribine, interferon alpha, pegylated interferon, or antibody therapy <28 days or 5 half-lives of the drug (whichever is longer), before starting screening assessments
- Received radiotherapy or psoralen and ultraviolet A therapy <14 days before starting screening assessments
- Received any hematopoietic growth factor support <14 days or 5 half lives of the drug before starting screening assessments
- History of clinically significant bleeding event within 30 days before the first dose of study drug or need for therapeutic anticoagulation on study
- Need for treatment of corticosteroids at >10 mg/day of prednisone or equivalent
- Received strong CYP3A4 inhibitors or inducers within 14 days or 5 drug half-lives before the first dose of study drug
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description (Part 1b) Bezuclastinib Dose 1 + BSC Bezuclastinib Tablets (Formulation B) - (Part 1a) Bezuclastinib Dose 2 + BSC Bezuclastinib Tablets (Formulation A) - (Part 2) Placebo + BSC Placebo Tablets - (Part 3) Bezuclastinib + BSC Bezuclastinib Tablets (Formulation A) - (Part 1a) Bezuclastinib Dose 1 + BSC Bezuclastinib Tablets (Formulation A) - (Part 1a) Placebo + BSC Placebo Tablets - (Part 1b) Placebo + BSC Placebo Tablets - (Part 1b) Bezuclastinib Dose 2 + BSC Bezuclastinib Tablets (Formulation B) - (Part 2) Bezuclastinib Selected Dose + BSC Bezuclastinib Tablets (Formulation B) - (Part 3) Bezuclastinib + BSC Bezuclastinib Tablets (Formulation B) -
- Primary Outcome Measures
Name Time Method Part 1: Determine recommended dose of bezuclastinib (CGT9486) in subjects with NonAdvSM 3 months Selection of the recommended dose to be used in subsequent parts of the study.
Part 2: Efficacy of bezuclastinib at the selected dose versus placebo 24 Weeks Mean absolute change on the Mastocytosis Symptom Severity Daily Diary (MS2D2)
Part 3: Safety and tolerability of bezuclastinib as assessed by number of adverse events Up to 5 years CTCAE v5
- Secondary Outcome Measures
Name Time Method Part 3: Change and percent change in the levels of KIT D816V mutation allele burden Up to 12 months Parts 2 & 3: Determine change of the lead (most severe) symptom and lead (most severe) subdomain of the MS2D2 in subjects treated with bezuclastinib versus placebo Up to 5 years Change and percent change from baseline in the symptom score of the subject's most severe symptom.
Change and percent change from baseline in the MS2D2 subdomain score of the subject's most severe subdomain.Part 2: Proportion of subjects who had at least 50% reduction in serum tryptase 24 weeks Part 2: Proportion of subjects who had at least a 50% reduction in peripheral blood D816V allele fraction 24 weeks Part 2: Determine responder rates of subjects treated with bezuclastinib at the selected dose versus placebo 24 weeks Proportion of subjects with at least a 30% reduction of the total symptom score (TSS) on the MS2D2.
Proportion of subjects with at least a 50% reduction of the total symptom score (TSS) on the MS2D2.Part 2: Proportion of subjects who had at least 50% reduction in mast cell burden 24 weeks Parts 1 & 2: Safety and tolerability of bezuclastinib as assessed by number of adverse events Up to 24 weeks CTCAE v5
Parts 1, 2, & 3: Change and percent change in patient reported outcome (PRO) measures Up to 5 years Parts 1 & 3: Change and percent change in serum tryptase Up to 12 months Parts 1 & 3: Change and percent change in bone marrow mast cells Up to 18 months Part 1: Assess the pharmacokinetics (PK) of bezuclastinib in subjects with NonAdvSM 3 months Plasma concentrations of CGT9846
Part 2: Determine mean change from baseline in predetermined PRO sub-domain and individual item scores 24 weeks Part 3: To determine the efficacy of bezuclastinib at the selected dose Up to 2 years Proportion of subjects with at least a 50% reduction in MS2D2 TSS from baseline at 1 year and 2 years from start of bezuclastinib
Change and percent change from baseline in the MS2D2 TSS, subdomain, and individual item scoresPart 3: Usage of concomitant medications as rescue therapy for NonAdvSM and changes from baseline in rescue therapy and best supportive care medications regimen Up to 5 years
Trial Locations
- Locations (69)
University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States
Mayo Clinic Arizona
🇺🇸Phoenix, Arizona, United States
One of a Kind Clinical Research Center
🇺🇸Scottsdale, Arizona, United States
Modena Allergy and Asthma Clinical
🇺🇸La Jolla, California, United States
University of California, Los Angeles (UCLA) - Medical Center
🇺🇸Los Angeles, California, United States
Innovative Research of West Florida
🇺🇸Clearwater, Florida, United States
Mayo Clinic - Jacksonville
🇺🇸Jacksonville, Florida, United States
University of South Florida
🇺🇸Tampa, Florida, United States
Emory University
🇺🇸Atlanta, Georgia, United States
Rush University
🇺🇸Chicago, Illinois, United States
Walter Reed National Military Medical Center
🇺🇸Bethesda, Maryland, United States
Allervie Clinical Research
🇺🇸Glenn Dale, Maryland, United States
Institute for Asthma and Allergy
🇺🇸Wheaton, Maryland, United States
Chesapeake Research Center
🇺🇸White Marsh, Maryland, United States
Brigham and Women's Hospital
🇺🇸Boston, Massachusetts, United States
Dana Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
University of Michigan
🇺🇸Ann Arbor, Michigan, United States
Mayo Clinic- Rochester
🇺🇸Rochester, Minnesota, United States
Washington University at St. Louis
🇺🇸Saint Louis, Missouri, United States
Dartmouth Hitchcock Medical Center
🇺🇸Lebanon, New Hampshire, United States
Icahn School of Medicine at Mount Sinai
🇺🇸New York, New York, United States
Duke University
🇺🇸Raleigh, North Carolina, United States
University of Cincinnati
🇺🇸Cincinnati, Ohio, United States
The Ohio State University
🇺🇸Columbus, Ohio, United States
Medical University of South Carolina
🇺🇸Charleston, South Carolina, United States
Vanderbilt University Medical Center
🇺🇸Nashville, Tennessee, United States
AIR Care
🇺🇸Dallas, Texas, United States
The University of Texas MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
Metrodora Institute of Technology
🇺🇸West Valley City, Utah, United States
Royal Prince Alfred Hospital
🇦🇺Camperdown, New South Wales, Australia
Royal Adelaide Hospital
🇦🇺Adelaide, South Australia, Australia
Kepler Universitaetsklinikum GmbH
🇦🇹Linz, Austria
Medizinische Universitaet Wien
🇦🇹Wien, Austria
Antwerp University Hospital (UZA)
🇧🇪Edegem, Belgium
CHU Tivoli
🇧🇪La Louvière, Belgium
Tom Baker Cancer Centre
🇨🇦Calgary, Alberta, Canada
University of Alberta
🇨🇦Edmonton, Alberta, Canada
St. Michael's Hospital
🇨🇦Toronto, Ontario, Canada
McGill University
🇨🇦Montréal, Quebec, Canada
Fakultni nemocnice Kralovske Vinohrady
🇨🇿Praha 10, Czechia
AP-HM - Hopital de la Timone
🇫🇷Marseille, France
AP-HP- Hopital Pitie-Salpetriere
🇫🇷Paris, France
CHU de Toulouse - Hopital Larrey
🇫🇷Toulouse, France
Universitaetsklinikum Aachen, AoeR
🇩🇪Aachen, Germany
Charité Universitätsmedizin Berlin
🇩🇪Berlin, Germany
Universitaetsklinikum Hamburg-Eppendorf
🇩🇪Hamburg, Germany
Universitätsklinikum Schleswig-Holstein
🇩🇪Kiel, Germany
University Medical Centre Mannheim
🇩🇪Mannheim, Germany
Attikon University General Hospital Athens
🇬🇷Athens, Greece
Cork University Hospital
🇮🇪Cork, Ireland
St. James's Hospital
🇮🇪Dublin, Ireland
IRCCS Azienda Ospedaliero-Universitaria di Bologna - Policlinico di Sant'Orsola
🇮🇹Bologna, Italy
AOU Policlinico Rodolico San Marco
🇮🇹Catania, Italy
Azienda Ospedaliero-Universitaria Careggi
🇮🇹Firenze, Italy
Fondazione IRCCS Policlinico San Matteo
🇮🇹Pavia, Italy
AUSL della Romagna-Ospedale S.Maria delle Croci
🇮🇹Ravenna, Italy
Policlinico Universitario Agostino Gemelli
🇮🇹Rome, Italy
Azienda Ospedaliera Universitaria Integrata Verona-Ospedale Borgo Trento
🇮🇹Verona, Italy
University Medical Center Groningen
🇳🇱Groningen, Netherlands
Erasmus Rotterdam
🇳🇱Rotterdam, Netherlands
Oslo University Hospital
🇳🇴Oslo, Norway
Uniwersyteckie Centrum Kliniczne, Klinika Hematologii i Transplantologii
🇵🇱Gdańsk, Poland
Samodzielny Publiczny Szpital Kliniczny Nr 1 - Klinika Hematoonkologii i Transplantacji Szpiku
🇵🇱Lublin, Poland
Hospital Universitario Vall d'Hebron
🇪🇸Barcelona, Spain
Institut Catala d'Oncologia - L'Hospitalet
🇪🇸Barcelona, Spain
Hospital Universitario Ramon y Cajal
🇪🇸Madrid, Spain
Instituto de Estudios de Mastocitosis de Castilla La Mancha-Hospital Virgen del Valle
🇪🇸Toledo, Spain
University Hospital Basel
🇨🇭Basel, Switzerland
Guy's Hospital
🇬🇧London, United Kingdom