Advanced Mastocytosis mast cell accumulation myeloid neoplasm
Conditions
Interventions
In Part 1 of the study, approximately 28 subjects will be randomized to 1 of 4
dose cohorts of bezuclastinib Formulation A. Subjects will be randomized in a
1:1:1:1 manner.
Part 2 will be conducted
Sponsors
Cogent Biosciences, Inc.
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1. Diagnosed with 1 of the following advanced mastocytosis diagnoses by Eligibility Committee a. Aggressive Systemic Mastocytosis (ASM) b. Systemic Mastocytosis with an Associated Hematologic Neoplasm (SM-AHN) c. 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.
Exclusion criteria
Exclusion criteria: 1. Persistent toxicity from previous therapy for Advanced Systemic Mastocytosis that has not resolved to
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Part 1 Safety assessments and dose modifications Pharmacokinetics (PK) and pharmacodynamic assessments Overall Response Rate (ORR) Part 2 Stage 1 • Safety assessments and dose modifications • PK and pharmacodynamic assessments • Overall Response Rate (ORR) Part 2 Stage 2 ORR | — |
Secondary
| Measure | Time frame |
|---|---|
| Incidence of AEs, SAEs, AEs leading to dose modifications, and changes from baseline in laboratory results Duration of response (DOR), defined as the date of the first documented response (CR, CRh, PR, or CI) to date of first documented and confirmed disease progression or death from any cause, whichever occurs first, based on modified IWG-MRT-ECNM response criteria Time to response (TTR), defined as the date of first dose of study drug to the date of the first documented response (CR, CRh, PR, or CI) based on modified IWG-MRT-ECNM response criteria Progression-free survival (PFS), defined as the date of first dose of study drug to the date of first documented confirmed disease progression or death from any cause, whichever occurs first Overall survival (OS), defined as the date of first dose of study drug to the date of death from any cause Pure Pathologic Response (PPR), including complete remission, complete remission with partial recovery of peripheral blood, and partial remission (Gotlib et al, 2020) Changes in spleen and liver size assessed by magnetic resonance imaging (MRI) Changes in the levels of serum tryptase Changes in the levels of KIT D816V mutation allele burden in blood and bone marrow Change in pathologic findings in the blood and bone marrow including mast cell infiltration, monocytosis, and eosinophilia Plasma concentrations of bezuclastinib Patient Global Impression of Change (PGIC) scale and change and percent change from baseline in the following patient-reported outcome measures: Patient Global Impression of Severity (PGIS) scale, Mastocytosis Quality of Life Questionnaire (MC-QoL), and Mastocytosis Activity Score (MAS) where appropriate translations are available (Siebenhaar et al, 2018; Siebenhaar et al, 2016) Incidence of AEs, SAEs, AEs leading to dose modifications, and changes from baseline in laboratory results PPR, including complete remission, complete remission with partial hematologic recovery, molecu | — |
Countries
Netherlands
Outcome results
None listed