Ivosidenib as Maintenance Therapy in Transplant-Ineligible IDH1-mutated AML and HR-MDS

A Phase II, Multicenter, Open-label Clinical Study of Ivosidenib as Maintenance Therapy in Patients With IDH1-mutated AML and High-risk MDS Who Are Ineligible for Transplantation (IVORY-MAST)

This study will explore the efficacy and safety of ivosidenib as maintenance therapy in patients with IDH1-mutated AML and high-risk MDS who are ineligible for transplantation, along with accompanying molecular biomarker research. Patients who meet the eligibility criteria will receive ivosidenib treatment until disease progression or unacceptable toxicity. This study will provide an effective maintenance treatment option for transplant-ineligible patients with IDH1-mutated AML and high-risk MDS.

Inclusion Criteria:

• Age ≥18 years, male or female.
• Molecularly confirmed diagnosis of IDH1-mutated acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome (MDS).
• Achieved complete remission (CR) or partial remission (PR) after induction therapy.
• Ineligible for allogeneic hematopoietic stem cell transplantation (allo-HSCT).
• Eastern Cooperative Oncology Group (ECOG) performance status score ≤2.
• Signed informed consent.
• For women of childbearing potential: must have practiced contraception for at least one month prior to screening and commit to using contraception throughout the study period and for the required period after study completion.
• Female participants of childbearing potential and male participants with female partners of childbearing potential must agree to use highly effective methods of contraception from the time of signing informed consent until 180 days after the last dose of the study drug.

Exclusion Criteria:

Participants with any of the following criteria will be excluded from the study:

• Prior treatment with an IDH1 inhibitor.
• Diagnosis of M3 subtype (acute promyelocytic leukemia, APL).
• Presence of severe hepatic or renal dysfunction.
• Active infection or other serious comorbidities.
• Major surgery within 28 days prior to the first dose, or planned surgery during the study period.
• Diagnosis of any other malignancy within 5 years prior to the first dose, with the exception of early-stage malignancies that have been cured by radical treatment, such as carcinoma in situ of the lung, non-melanoma skin cancer, basal cell or squamous cell carcinoma of the skin, or cervical carcinoma in situ. Whether to exclude such patients will be determined by the investigator's assessment.
• Severe cardiovascular disease, such as New York Heart Association (NYHA) class 2 heart failure, unstable angina, unstable arrhythmia, myocardial infarction or cerebrovascular accident within 3 months prior to randomization.
• Human immunodeficiency virus (HIV) infection or known acquired immunodeficiency syndrome (AIDS); active hepatitis B (HBV DNA≥1000 IU/ml); hepatitis C (positive for anti-HCV antibodies and HCV-RNA above the lower limit of detection of the assay); or co-infection with hepatitis B and hepatitis C.
• Known history of psychoactive substance abuse or drug addiction.
• Presence of any other serious physical or mental illness, or abnormal laboratory findings that may increase the risk of study participation, interfere with the study results, or make the patient unsuitable for study participation in the opinion of the investigator.
• Inability to swallow, intestinal obstruction, or other factors affecting drug administration or absorption.
• Previous concomitant treatment with both drugs of the combination therapy targeting the same pathway as in this study.
• History of allergy to the study drug or any of its excipients.