IVOSIDENIB for Acute myeloid leukaemia | IDH1-mutated acute myeloid leukaemia

Inclusion criteria

• {"criterion_text":"- Male or female ≥ 55 years of age at the time of signing informed consent"}
• {"criterion_text":"- Absence of any psychological, familial, sociological, or geographical conditions potentially hampering compliance with the study protocol and follow-up schedule"}
• {"criterion_text":"- Patient suitable for oral administration of study drug."}
• {"criterion_text":"- A female subject is eligible to participate if she is not pregnant and at least one of the following conditions applies: a. Not a woman of childbearing potential (WOCBP) as defined in post-menopausal (defined as at least 1 year without any menses) prior to Screening, or documented as surgically sterile (at least 1 month prior to Screening); b. WOCBP agrees to follow the contraceptive treatment starting at screening and continued throughout the study period, and for at least 180 days after the final study drug administration; c. WOCBP agrees to perform planned pregnancy tests in the study"}
• {"criterion_text":"- Female subject must agree not to breastfeed starting at screening and throughout the study period, and for one month after the final study drug administration."}
• {"criterion_text":"- Female subject must not donate ova starting at screening and throughout the study period, and for 180 days after the final study drug administration."}
• {"criterion_text":"- A male subject with a partner(s) of childbearing potential must agree to use contraception starting at screening and continue throughout the study period, for at least 90 days after the final study drug administration."}
• {"criterion_text":"- A male subject must not donate sperm starting at screening nor throughout the study period and for 90 days after the final study drug administration"}
• {"criterion_text":"- Patient must be affiliated to the French social security (health insurance)"}
• {"criterion_text":"- Signed written informed consent for the study"}
• {"criterion_text":"- Patients with confirmation of newly diagnosed AML by 2022 WHO criteria"}
• {"criterion_text":"- Presence of IDH1 R132 mutation at AML diagnosis"}
• {"criterion_text":"- Achievement CR or CRi following induction therapy by intensive chemotherapy (according to ELN 2022), within 17 weeks prior to enrollment."}
• {"criterion_text":"- Received at least 2 consolidations : a.\twith intermediate dose of cytarabine (IDAC); b. or with standard dose cytarabine and idarubicin (5+1)"}
• {"criterion_text":"- Adequate BM function: ANC ≥1 × 109/L and platelet count ≥50 × 109/L at the time of inclusion"}
• {"criterion_text":"- Patients who are not candidate for Allo-HSCT"}
• {"criterion_text":"- Adequate baseline organ function defined by the following criteria: - Estimated Glomerular Filtration Rate (eGFR) ≥ 30 ml/min (using CKD-EPI); -\taspartate aminotransferase (AST) ≤ 2.5 × ULN ; -\talanine aminotransferase (ALT) ≤ 2.5× ULN ; - bilirubin ≤ 1.5 × ULN"}
• {"criterion_text":"- ECOG < 3"}

Exclusion criteria

• {"criterion_text":"- Acute promyelocytic leukemia (FAB M3) with t(15;17) or its molecular equivalents (PML::RARA)"}
• {"criterion_text":"- Subject known to be positive for hepatitis B virus (HBV), or hepatitis C virus (HCV) infection. Inactive hepatitis carrier status with undetectable PCR viral load on antivirals (non-exclusionary medications) are not excluded."}
• {"criterion_text":"- AML associated with t(9;22) or molecular evidence of such a translocation"}
• {"criterion_text":"- Prior BM or hematopoietic stem cell transplantation"}
• {"criterion_text":"- CR/CRi following treatment with hypomethylating agents"}
• {"criterion_text":"- Proven central nervous system leukemia"}
• {"criterion_text":"- Candidate for Allo-HSCT at screening"}
• {"criterion_text":"- Diagnosis of malignant disease within the previous 12 months (excluding MDS or CMML, basal cell carcinoma of the skin without complications, “in- situ” carcinoma of the cervix or breast, or other local malignancy excised or irradiated with a high probability of cure)"}
• {"criterion_text":"- Abnormal cardiac status with any of the following: - Unstable angina ; - Myocardial infarction within the last 6 months ; - Significant cardiac arrhythmia ; - New York Heart Association (NYHA) class 3 or 4 congestive heart failure ; - Congenital long QT syndrome, familial history of sudden death or polymorphic ventricular arrhythmias and QT/QTc interval > 500 msec regardless of the correction method. For subject with 450 ≤ QTc ≤ 500 ms, practitioners should thoroughly reassess the benefit/risk of initiating ivosidenib. In case QTc interval prolongation is between 480 msec and 500 msec, initiation of treatment with ivosidenib should remain exceptional and be accompanied by close monitoring. This issue will be discuss with coordinating investigator."}
• {"criterion_text":"- Uncontrolled systemic fungal, bacterial or viral infection (defined as ongoing signs/symptoms related to the infection without improvement despite appropriate antibiotics or other treatment)"}
• {"criterion_text":"- Subject with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption"}
• {"criterion_text":"- Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study"}
• {"criterion_text":"- Severe medical or mental condition precluding the administration of protocol treatments"}
• {"criterion_text":"- Persons deprived of their liberty by judicial or administrative decision, persons subject to a legal protection measure (guardianship, curatorship, legal protection), persons under psychiatric care"}
• {"criterion_text":"- Other comorbidity that the physician judges to be incompatible with the study design"}
• {"criterion_text":"- Any condition causing an inability to swallow tablets or known hypersensitivity to the study medication"}
• {"criterion_text":"- Any condition that would impair absorption of the study medication (i.e. short gut, malabsorption syndrome)"}
• {"criterion_text":"- Subject requiring treatment with concomitant drugs that are strong inducers/inhibitors of cytochrome P450 (CYP)3A /PGP or dabigatran (PGP substrate) (see appendix 6) or QT-prolongating agent other than 5-HT3 antagonists (see appendix 8) or other forbidden medications listed in section 10.7."}
• {"criterion_text":"- Subject with positive HIV test treated or planned to be treated with drugs with potential drug-drug interactions. HIV testing will be performed at screening, if required per local guidelines or institutional standards."}

Primary endpoints

• {"endpoint_text":"- Relapse-free-survival (RFS) at 24 months in patients receiving oral azacitidine with ivosidenib.","definition_or_measurement_approach":"Relapse-free-survival (RFS) measured at 24 months in patients receiving oral azacitidine with ivosidenib."}

Secondary endpoints

• {"endpoint_text":"- RFS at 12 months, with the same definition for RFS as for the primary endpoint.","definition_or_measurement_approach":"RFS at 12 months; measured with the same RFS definition as for the primary endpoint."}
• {"endpoint_text":"- Overall survival defined as the time between inclusion assignment and death from any cause, at 12 and 24 months. Patients alive will be censored at the date of last news, or data cutoff.","definition_or_measurement_approach":"Overall survival (OS) defined as time from inclusion to death from any cause; assessed at 12 and 24 months; patients alive censored at last contact or data cutoff."}
• {"endpoint_text":"- EFS MRD-, defined in patients who were MRD negative at baseline as the time from inclusion to MRD relapse (by FCM or RT-qPC for NPM1) or death from any cause, whichever occurred first. Patients alive without MRD relapse will be censored at the date of last MRD assessment.","definition_or_measurement_approach":"EFS MRD- measured as time from inclusion to MRD relapse (by flow cytometry or RT-qPCR for NPM1) or death, whichever first; MRD-negative patients at baseline considered; censoring at last MRD assessment for patients without MRD relapse."}
• {"endpoint_text":"- Number of participants with Treatment Emergent Adverse Events (TEAEs), according the CTCAE v5.0 classification.","definition_or_measurement_approach":"Count of participants with TEAEs graded per CTCAE v5.0."}

France

Earliest CTIS Part Ii Submission Date

21-10-2025

Latest Decision Or Authorization Date

01-04-2026

Processing Time Days

162

Number Of Sites

20

Number Of Participants

60

Primary sponsor

Full Name

French Innovative Leukemia Organization

Organisation Type

Laboratory/Research/Testing facility

Country Of Registered Address

France

Third parties

• {"country":"France","full_name":"Centre Hospitalier Universitaire De Bordeaux","duties_or_roles":"code:4","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"France","full_name":"Silicon Marketing","duties_or_roles":"code:15 (DPO)","organisation_type":"Pharmaceutical company"}
• {"country":"France","full_name":"Acute Leukemia French Association-Clinical Research","duties_or_roles":"code:1","organisation_type":"Patient organisation/association"}
• {"country":"France","full_name":"Eurofins Clinical Trial Supplies France","duties_or_roles":"code:14; code:15 (Labelling, Packaging, QP certification and QP release)","organisation_type":"Pharmaceutical company"}
• {"country":"France","full_name":"For Drug Consulting","duties_or_roles":"code:8","organisation_type":"Pharmaceutical company"}
• {"country":"France","full_name":"Quanticsoft","duties_or_roles":"code:7","organisation_type":"Pharmaceutical company"}
• {"country":"France","full_name":"Oxmo Cdm","duties_or_roles":"code:6","organisation_type":"Non-Pharmaceutical company"}