Mutant IDH1 Inhibitor Olutasidenib Clinical Trial
Official title:
Phase 1b/2 Study of Decitabine and Venetoclax in Combination With the Targeted Mutant IDH1 Inhibitor Olutasidenib
To find a recommended combination dose of decitabine and venetoclax that can be given in combination with olutasidenib to participants with AML.
Primary Objectives - Phase 1b: To determine the safety and tolerability and recommended phase 2 dose (RP2D) of decitabine (either IV or oral decitabine/cedazuridine (ASTX727, Inqovi)) and venetoclax in combination with olutasidenib. - Phase 2: To determine the composite remission rate (CR, CRh and CRi) of decitabine (IV or oral decitabine/cedazuridine (ASTX727, Inqovi)) and venetoclax in combination with olutasidenib for newly diagnosed (Arm A) or relapsed/refractory (Arm B) participants with IDH1-mutated myeloid malignancy. Secondary Objectives - To determine duration of response (DOR), event-free survival (EFS), and overall survival (OS) - To evaluate occurrence of minimal residual disease (MRD) negative status by multiparameter flow cytometry and molecular evaluation. - To determine the overall response rate (CR, CRh, CRi, MLFS, and PR) - To characterize the pharmacokinetic (PK) profiles of venetoclax and olutasidenib in plasma samples (Phase 1b only). Exploratory Objectives - To investigate global gene expression profiles, DNA methylation profiles, BH3 profiling and other potential prognostic markers to explore predictors of antitumor activity and/or resistance to treatment. ;