Ivosidenib Combined With Venetoclax and Azacitidine for the Treatment of Newly Diagnosed IDH1 Mutation Acute Myeloid Leukemia: a Prospective, Single-arm, Two-cohorts, Study
This is a single arm, open-label, multicenter clinical trial to evaluate the efficacy and safety of ivosidenib+venetoclax+ azacitidine in adult Chinese subjects with newly diagnosed IDH1m AML.A total of approximately 42 China Nationwide subjects with newly diagnosed IDH1m AML will participate in the study.The primary endpoint of the study is the complete remission(CR) + CR with partial hematologic recovery(CRh) rate, and the key secondary endpoints are CR rate,event-free survival (EFS),overall survival (OS),the objective response rate (ORR).
• Be ≥18 years of age
• Have previously untreated AML, defined according to World Health Organization criteria. Subjects with extramedullary disease alone (ie, no detectable bone marrow and no detectable peripheral blood AML) are not eligible for the study.
• Have an IDHl mutation resulting in an R132C, R132G, R132H, R132L, or R132S substitution.
• Have an ECOG PS score of 0 to 2.
• Have adequate hepatic function, as evidenced by:
‣ Serum total bilirubin ≤2 × ULN, unless considered to be due to Gilbert's disease or underlying leukemia, where it must be \<3 x ULN.
⁃ Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) ≤3.0 × ULN, unless considered to be due to underlying leukemia.
• Have adequate renal function, as evidenced by serum creatinine ≤2.0 x ULN or creatinine clearance \>30 mL/min based on the Cockcroft-Gault glomerular filtration rate.
• Have agreed to undergo serial blood and bone marrow sampling.
• Be able to understand and willing to sign an informed consent form.
• Be willing to complete QoL assessments during study treatment and at the designated time points following treatment discontinuation.
⁃ If female with reproductive potential, must have a negative serum pregnancy test prior to the start of study therapy. Female subjects with reproductive potential are defined as sexually mature women who have not undergone a hysterectomy, bilateral oophorectomy, or tubal occlusion or who have not been naturally postmenopausal for at least 24 consecutive months. Females of reproductive potential, as well as fertile men with female partners of reproductive potential, must use 2 effective forms of contraception (including at least 1 barrier form) from the time of giving informed consent throughout the study and for 90 days (both females and males) following the last dose of study drugs). Effective forms of contraception are defined as hormonal oral contraceptives, injectables, patches, intrauterine devices, intrauterine hormone-releasing systems, bilateral tubal ligation, condoms with spermicide, or male partner sterilization.