Ivosidenib for Acute myeloid leukemia (AML) | Myelodysplastic syndromes (MDS)

Inclusion criteria

• {"criterion_text":"- Age ≥ 18 years\n- Negative serum pregnancy test\n- Male subjects must agree to refrain from unprotected sex and sperm donation from time point of signing the informed consent until 1 month after the last dose of the investigational medicinal product\n- Willingness and ability to comply with all study procedures\n- Informed consent signed by the patient capable of giving\n- Eastern Cooperative Group (ECOG) performance status ≤\n- AML or MDS according to WHO criteria with IDH1 mutation\n- having received alloSCT within the past 100 days\n- documented CR, CRi, CRh or MLFS after alloSCT within 28 days prior to enrolment (documented by bone marrow aspiration)\n- Adequate organ function defined by: Serum creatinine clearance > 30 mL/min; calculated by the Cockcroft Gault formula\n- Adequate organ function defined by: Serum total bilirubin ≤2 × ULN, unless considered to be due to Gilbert’s disease\n- Adequate organ function defined by: Left ventricular ejection fraction (LVEF) ≥ 35%"}

Exclusion criteria

• {"criterion_text":"- Active acute GvHD grade III-IV according to Harris criteria requiring steroids > 1 mg/kg prednisolone equivalent\n- Indications that the subject is unlikely to adhere to the protocol (e.g., lack of compliance)\n- Substance abuse, medical, psychological, or social conditions that may interfere with the subject’s cooperation with the requirements of the trial or evaluation of the study results\n- Significant cardiac disease: i.e., heart failure NYHA III or IV; unstable angina pectoris; recent myocardial infarction or clinically significant bradycardia\n- Long QT syndrome (QTcF ≥480 msec on screening ECG)\n- Concurrent use of medications that have a relative risk of prolonging QT interval or of inducing Torsade de Pointes unless it is secured that if patient receive medications with known QT interval prolonging potential concomitantly, ECG monitoring has to be conducted weekly, or more frequently based on institutional standards or investigator discretion for the first 3 weeks following initiation of Ivosidenib treatment\n- Pulmonary disease with clinically relevant hypoxia (need for oxygen inhalation)\n- Patients undergoing renal dialysis\n- Active severe or uncontrolled infection\n- Any condition that limits the ingestion or gastrointestinal absorption of orally administered drugs\n- Diagnosis of another primary malignancy that is currently clinically significant or currently requires active treatment / intervention\n- Hypersensitivity known from medical history to Ivosidenib or its ingredients or to drugs with a similar chemical structure\n- Concomitant administration of dabigatran and/or a familial history of sudden death or polymorphic ventricular arrhythmia and/or the rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption\n- Having received any unlicensed drug within 30 days or 5 half-lives, whichever is greater, prior to enrolment\n- Addictions or other illnesses that do not allow the patient concerned to assess the nature and extent of the clinical trial and its possible consequences\n- Pregnant or breastfeeding women, breastfeeding has to be discontinued before onset of treatment and until for at least 1 month after the last dose\n- Patients who are unwilling to follow strictly highly effective contraception requirements including hormonal contraceptives with a Pearl Index < 1% per year in combination with a barrier method from time point of signing the informed consent until 1 month after the last dose of the IMP unless one of the following criteria is met: post-menopausal (12 months natural amenorrhoea or 6 months amenorrhoea with serum FSH > 40 U/ml)\n- Patients who are unwilling to follow strictly highly effective contraception requirements including hormonal contraceptives with a Pearl Index < 1% per year in combination with a barrier method from time point of signing the informed consent until 1 month after the last dose of the IMP unless one of the following criteria is met: postoperative (6 weeks after bilateral ovariectomy with or without hysterectomy)\n- Patients who are unwilling to follow strictly highly effective contraception requirements including hormonal contraceptives with a Pearl Index < 1% per year in combination with a barrier method from time point of signing the informed consent until 1 month after the last dose of the IMP unless one of the following criteria is met: medically confirmed ovarian failure\n- Patients who are unwilling to follow strictly highly effective contraception requirements including hormonal contraceptives with a Pearl Index < 1% per year in combination with a barrier method from time point of signing the informed consent until 1 month after the last dose of the IMP unless one of the following criteria is met: vasectomy of the partner"}

Primary endpoints

• {"endpoint_text":"- Rate of event-free survival (EFS) at two years after study inclusion. Events are defined as death from any cause or disease relapse defined as reappearance of leukemic blasts in peripheral blood or ≥ 5% bone marrow blasts or development of extramedullary disease as defined according to 1 or end of or initiation of any new anti-cancer therapy.","definition_or_measurement_approach":"EFS measured as rate at two years after study inclusion; events defined as death from any cause or disease relapse (reappearance of leukemic blasts in peripheral blood or ≥ 5% bone marrow blasts or development of extramedullary disease) or initiation of any new anti-cancer therapy."}

Secondary endpoints

• {"endpoint_text":"- Rate of overall survival (OS) at two years after study inclusion (written informed consent).","definition_or_measurement_approach":"OS rate at two years after study inclusion."}
• {"endpoint_text":"- EFS and OS as time-to-event analysis including follow-up.","definition_or_measurement_approach":"Time-to-event analyses for EFS and OS including follow-up."}
• {"endpoint_text":"- Rate of complete molecular remissions (CRMRD-) as defined by international consensus guidelines at 6, 12 and 24 months after study inclusion.","definition_or_measurement_approach":"CRMRD- rates at 6, 12 and 24 months per international consensus guidelines."}
• {"endpoint_text":"- MRD conversion rate from positive (CRMRD+) to negative (CRMRD−) as defined by international consensus guidelines among subjects with measurable residual disease at baseline.","definition_or_measurement_approach":"MRD conversion rate among subjects with measurable residual disease at baseline, per international consensus guidelines."}
• {"endpoint_text":"- Cumulative incidence of higher grade acute GvHD defined as new onset of or increase in severity to grade III-IV aGVHD as defined by investigator following international expert consensus guidelines .","definition_or_measurement_approach":"Cumulative incidence of grade III-IV acute GvHD as defined by investigator following international expert consensus guidelines."}
• {"endpoint_text":"- Cumulative incidence and maximal grade (according to international expert consensus guidelines) of chronic GvHD requiring systemic treatment within one year after alloSCT.","definition_or_measurement_approach":"Cumulative incidence and maximal grade of chronic GvHD requiring systemic treatment within one year after alloSCT per international guidelines."}
• {"endpoint_text":"- Cumulative incidence of AEs/SAEs Grade ≥3 or leading to dose reduction/discontinuation of study treatment.","definition_or_measurement_approach":"Cumulative incidence of grade ≥3 AEs/SAEs or those leading to dose reduction/discontinuation."}
• {"endpoint_text":"- Cumulative incidences of non-relapse mortality within 100 days and 2 years from study inclusion defined as death that was not proceeded by recurrent or progressive malignancy.","definition_or_measurement_approach":"Cumulative incidences of non-relapse mortality at 100 days and 2 years from study inclusion."}
• {"endpoint_text":"- Cumulative incidence of relapse mortality within 2 years from study inclusion.","definition_or_measurement_approach":"Cumulative incidence of relapse mortality within 2 years from study inclusion."}
• {"endpoint_text":"- Number of patients who require dose reductions or have to stop study treatment due to toxicity reasons.","definition_or_measurement_approach":"Count of patients requiring dose reductions or stopping treatment due to toxicity."}

Germany

Earliest CTIS Part Ii Submission Date

20-03-2025

Latest Decision Or Authorization Date

10-04-2026

Processing Time Days

386

Number Of Sites

15

Number Of Participants

76

Primary sponsor

Full Name

Technische Universitat Dresden

Organisation Type

Educational Institution

Country Of Registered Address

Germany

Third parties

• {"country":"","full_name":"Servier (Servier Affaires Médicales and Servier Deutschland GmbH)","duties_or_roles":"Source of monetary support","organisation_type":""}
• {"country":"","full_name":"LES LABORATOIRES SERVIER (SURESNES)","duties_or_roles":"Product marketing authorization holder / product supplier (product listed: Tibsovo 250 mg film-coated tablets)","organisation_type":""}