Aggressive Systemic Mastocytosis (ASM) Clinical Trial
Official title:
A Phase 2 Open-Label, Multicenter Clinical Study of the Safety, Efficacy, Pharmacokinetic, and Pharmacodynamic Profiles of CGT9486 as a Single Agent in Patients With Advanced Systemic Mastocytosis
This is an open-label, two-part Phase 2 study investigating CGT9486 for the treatment of patients with Advanced Systemic Mastocytosis (AdvSM), including patients with Aggressive SM (ASM), SM with Associated Hematologic Neoplasm (SM-AHN), and Mast Cell Leukemia (MCL).
| Status | Recruiting |
| Enrollment | 140 |
| Est. completion date | September 2025 |
| Est. primary completion date | January 2025 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years and older |
| Eligibility | Key Inclusion Criteria for Main Study: 1. Diagnosed with one of the following advanced mastocytosis diagnoses by Eligibility Committee 1. Aggressive Systemic Mastocytosis (ASM) 2. Systemic Mastocytosis with an Associated Hematologic Neoplasm (SM-AHN) 3. Mast Cell Leukemia (MCL) 2. Measurable disease according to modified IWG-MRT-ECNM criteria. (A subset of patients inevaluble per mIWG-MRT-ECNM will be included in the study). 3. ECOG (0 to 3) 4. Have clinically acceptable local laboratory screening results (clinical chemistry, hematology) within certain limits Key Exclusion Criteria for Main Study: 1. Persistent toxicity from previous therapy for AdvSM that has not resolved to = Grade 1 2. Associated hematologic neoplasm requiring immediate antineoplastic therapy 3. Clinically significant cardiac disease 4. Known positivity for the FIP1L1 PDGFRA fusion. Patients with eosinophilia without detectable KIT D816V mutation must demonstrate lack of PDGFRA fusion mutation prior to enrollment 5. Seropositive for human immunodeficiency virus (HIV) 1 or 2, or positive for hepatitis B surface antigen or hepatitis C virus (HCV) antibody 6. History of clinically significant bleeding event within 30 days before the first dose of study drug or need for therapeutic anticoagulation on study 7. Diagnosed with or treated for malignancy other than the disease under study within the prior 3 years before enrollment 8. Received any cytoreductive therapy or any investigational agent less than 14 days, and for cladribine, interferon alpha, pegylated interferon, and any antibody therapy less than 28 days, before screening bone marrow biopsy 9. Received hematopoietic growth factor support within 14 days before the first dose of study drug 10. Received strong CYP3A4 inhibitors or inducers within 14 days or 5 drug half-lives, whichever is longer, before the first dose of study drug 11. Need for treatment with high dose steroids Key Inclusion Criteria for Substudy Population: Rollover Cohort 1. Demonstrate AHN progression requiring immediate AHN-directed therapy while receiving bezuclastinib 2. Demonstrated clinical benefit from bezuclastinib therapy 3. Have clinically acceptable local laboratory screening results (clinical chemistry, hematology) within certain limits High-Risk Cohort 1. Receiving or indicated for AHN-directed therapy. 2. Diagnosed with one of the following pathologic diagnoses of SM-AHN: 1. Myelodysplastic syndrome (MDS) that is high- or very high-risk 2. Accelerated phase myeloproliferative neoplasm (MPN) 3. MDS with excessive blasts in bone marrow or peripheral blood 4. Chronic myelomonocytic leukemia-2 (CMML-2) 3. Have clinically acceptable local laboratory screening results (clinical chemistry, hematology) within certain limits. Key Exclusion Criteria for Substudy Population: 1. Diagnosis of Philadelphia chromosome-positive malignancy 2. Diagnosis of acute myeloid leukemia (AML) 3. Appropriate for allogenic hematopoietic stem cell transplantation 4. Any contraindication to selected concomitant therapy 5. Rollover Cohort: Have not demonstrated acceptable tolerability of previous bezuclastinib therapy 6. High-Risk Cohort: Previously treated with investigational therapy for AdvSM 7. High-Risk Cohort: Previously treated with cytoreductive therapy and discontinued due to treatment-related toxicity 8. High-Risk Cohort: Received any cytoreductive therapy or any investigational agent less than 14 days, and for cladribine, interferon alpha, pegylated interferon, and any antibody therapy less than 28 days, before screening or archival bone marrow biopsy |
| Country | Name | City | State |
|---|---|---|---|
| Australia | Nepean Hospital | Kingswood | New South Wales |
| Australia | Peter MacCallum Cancer Centre | Melbourne N. | Victoria |
| Australia | Gold Coast University Hospital | Southport | Queensland |
| Austria | AKH Wien, Universitatsklinikum | Vienna | |
| Belgium | CHU de Liege | Liège | |
| Canada | University of Alberta Hospital | Edmonton | Alberta |
| Canada | St. Michael's Hospital - Unity Health Toronto | Toronto | Ontario |
| France | Necker-Enfants Malades Hospital | Paris | |
| France | Centre Hospitalier Universitaire (CHU) de Poitiers | Poitiers | |
| France | Centre Hospitalier Universitaire (CHU) de Toulouse | Toulouse | |
| Germany | University Hospital Aachen | Aachen | |
| Germany | Universitätsklinikum Freiburg | Freiburg | |
| Germany | Universitätsklinikum Mannheim | Mannheim | |
| Italy | IRCCS Azienda Ospedaliero Universitaria di Bologna | Bologna | |
| Italy | Azienda Ospidaleira Universitaria Integrata Verona | Verona | |
| Netherlands | University Medical Center Groningen | Groningen | |
| Norway | Oslo University Hospital | Oslo | |
| Spain | Hospital Universitario Vall d'Hebron | Barcelona | |
| Spain | Institut Català d'Oncologia - Hospital Duran i Reynals | Barcelona | |
| Spain | Hospital Universitario Ramón y Cajal | Madrid | |
| Switzerland | Universitätsspital Basel | Basel | |
| United Kingdom | Leeds Teaching Hospitals NHS Trust | Leeds | |
| United Kingdom | Guy's Hospital - NHS Foundation Trust | London | |
| United Kingdom | University College London Hospital - NHS Foundation Trust | London | |
| United States | Winship Cancer Institute - Emory University | Atlanta | Georgia |
| United States | University of Alabama at Birmingham (UAB) Hospital | Birmingham | Alabama |
| United States | Dana-Farber Cancer Institute | Boston | Massachusetts |
| United States | MUSC Health University Medical Center | Charleston | South Carolina |
| United States | Rush University Medical Center | Chicago | Illinois |
| United States | Cleveland Clinic Taussig Cancer Center | Cleveland | Ohio |
| United States | City of Hope Comprehensive Cancer Center | Duarte | California |
| United States | Galiz Research | Hialeah | Florida |
| United States | The University of Texas MD Anderson Cancer Center | Houston | Texas |
| United States | UCLA Medical Center | Los Angeles | California |
| United States | Columbia University Irving Medical Center | New York | New York |
| United States | Mayo Clinic Arizona | Phoenix | Arizona |
| United States | Huntsman Cancer Institute - University of Utah Health | Salt Lake City | Utah |
| United States | Stanford Cancer Institute | Stanford | California |
| Lead Sponsor | Collaborator |
|---|---|
| Cogent Biosciences, Inc. |
United States, Australia, Austria, Belgium, Canada, France, Germany, Italy, Netherlands, Norway, Spain, Switzerland, United Kingdom,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Part I: Identify clinically active and tolerable exposures of bezuclastinib in patients with AdvSM | 18 months | ||
| Primary | Part II: - Determine efficacy of bezuclastinib as measured by mIWG Objective Response Rate (ORR) - Confirm the exposure-response relationship of bezuclastinib | 18 months | ||
| Secondary | Pure Pathologic Response (PPR) | Months | 18 months | |
| Secondary | Safety of CGT9486 as assessed by incidence of Adverse Events (AEs) | Incidence of AEs according to CTCAE version 5.0 or higher | 18 months | |
| Secondary | To determine the effects of bezuclastinib on mutation allele burden. | Percentage change in KIT D816V | 18 months | |
| Secondary | To determine the effects of bezuclastinib on serum tryptase. | Percentage change in Serum Tryptase | 18 months | |
| Secondary | To assess the pharmacokinetics of bezuclastinib in subjects with AdvSM. | Percentage change in plasma concentrations of bezuclastinib | 18 months | |
| Secondary | Change from baseline in histopathologic findings in blood and bone marrow | Percentage change in mast cell infiltration in the bone marrow and percentage change in eosinophilia and monocytosis in the blood | 18 months | |
| Secondary | Change in spleen and liver volume by imaging | Percentage change | 18 months | |
| Secondary | Change in Patient Global Impression of Severity (PGIS) scale | 0 -10 points (higher values represent worse symptom outcomes) | 18 months | |
| Secondary | Change in Patient Global Impression of Change (PGIC) scale | 0 - 7 points (higher values represent better symptom outcomes) | 18 months | |
| Secondary | Change in Mastocytosis Quality of Life Questionnaire (MC-QoL) | 0 - 100 (higher values represent better symptom outcomes) | 18 months | |
| Secondary | Change in Mastocytosis Activity Score (MAS) | 0 - 252 (higher values represent worse symptom outcomes) | 18 months | |
| Secondary | Duration of Response (DOR) | Months | 18 months | |
| Secondary | Time to Response (TTR) | Months | 18 months | |
| Secondary | Progression Free Survival (PFS) | Months | 18 Months | |
| Secondary | Overall Survival (OS) | Months | 18 months |
| Status | Clinical Trial | Phase | |
|---|---|---|---|
| Completed |
NCT02380222 -
Patient-Reported Outcome Questionnaire for Systemic Mastocytosis
|
N/A |