Gilteritinib for Acute myeloid leukaemia

Inclusion criteria

• {"criterion_text":"- Patients must provide signed and dated informed consent for the study that has been approved by an Independent Ethics Committee (IEC) and the relevant Institution Review Board (IRB) of each participating centre, before performing any screening or study procedure.\n- Female patients of reproductive potential using hormonal contraceptives should add a barrier method of contraception.\n- Female subjects of child-bearing potential are eligible if they commit to contraception and if they are not pregnant, breastfeeding, nor considering becoming pregnant during the study or for at least 6 months after the last dose of Gilteritinib.\n- If male, and subject is sexually active with female partner(s) of childbearing potential, he must agree, to use effective contraception during treatment and for at least 4 months after the last dose of Gilteritinib.\n- Subjects must be willing and able to return to the clinical site for adequate follow-up and to comply with the protocol as required.\n- Patients with positive MRD (by PCR-NGS for FLT3-ITD) after 2 cycles of intensive chemotherapy in combination with an FLT3- inhibitor will be eligible for enrolment.\n- Adult male or female patients.. Aged 18 – 75 years old on the day of signing informed consent.\n- Subjects must have a new diagnosis of primary/de novoFLT3-ITD mutated AML according to the WHO criteria (2017).\n- Body weight >40kg.\n- Subjects must be willing and able to comply with the relevant procedures, according to the protocol.\n- Subjects must have an Eastern Cooperative Oncology Group (ECOG) performance status of < 2 (See Appendix 1: ECOG Performance Status).\n- Subjects must have an estimated life expectancy of >3 months.\n- Female patients of childbearing potential: negative serum pregnancy test at the screening visit and negative urine pregnancy test within seven days prior to starting treatment with Gilteritib.\n- Female patients of reproductive potential must agree to use an effective method of contraception during treatment with Gilteritinib and for at least 6 months after stopping Gilteritinib."}

Exclusion criteria

• {"criterion_text":"- Subjects with secondary AML, including treatment-related [e.g., due to prior anthracycline use], as well as subjects with progression of antecedent hematological disorder [e.g., MDS, MPN or MDS/MPN ‘overlap’ syndrome].\n- History of clinically significant medical conditions or any other reason that the investigator determines would interfere with the subject's participation in this study or would make the subject an unsuitable candidate to receive study drug.\n- Subjects with acute promyelocytic leukemia.\n- Subjects with a serious concurrent illness that in the opinion of the Investigator would pose an undue risk to the subject participating in the clinical study (such as active/uncontrolled infection at the time of screening).\n- Subjects with a diagnosis of human immunodeficiency virus (HIV), active hepatitis B virus (HBV) and/or hepatitis C virus (HCV) infection. Subjects with HBV inactive carrier status and/or HCV with low viral titres on antivirals (non-exclusionary medications) are eligible. Low viral hepatitis titre is defined per institutional guidelines.\n- Known hypersensitivity to the active substance or to any of the excipients of Gilteritinib.\n- Has a known psychiatric or substance abuse disorder that would interfere with the participant’s ability to cooperate with the requirements of the study.\n- Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 180 days after the last dose of Gilteritinib.\n- Patients not willing to comply with effective contraception.\n- Malabsorption syndrome or other condition that precludes oral route of administration."}

Primary endpoints

• {"endpoint_text":"- The rate of FLT3-ITD MRD negativity after 2 cycles of treatment with Gilteritinib.","definition_or_measurement_approach":"MRD negativity assessed by PCR-NGS for FLT3-ITD after 2 cycles of treatment."}

Secondary endpoints

• {"endpoint_text":"- Frequency and type of resistance mutations detected at relapse, with particular emphasis on the, RAS/MAPK pathway ( such as NRAS, KRAS, PTPN11, CBL, NF1).\n- Time to development of resistance (e.g., median duration of treatment before resistance is observed).\n- Phenotypic changes (via flow cytometry) associated with resistance. More specifically, phenotypes such as the CD34+CD38-CD123+ or the CD47, TIM-3, CD96 expression and the appearence/re-appearence of antigenic characterists will be evaluated.\n- Baseline biomarker profiles (gene expression, mutation profile, proteomics) correlated with treatment response. More specifically, the presence of co-mutations in DNMT3A, NPM1, TET2, ASXL1, TP53 and the expression of antiapoptotic genes (such as the BCL2 and the MCL1) will be evaluated.\n- Correlation between immune microenvironment features and response to treatment. More specifically, the expression of immunoregulatory molecules, such as the PD-L1, LAG-3, TIM-3 and the percentage of CD8+, T-regulatory and NK cells will be evaluated.\n- Predictive value of specific genomic or transcriptomic signatures for MRD negativity.","definition_or_measurement_approach":"Resistance mutations detected at relapse via genomic sequencing with emphasis on RAS/MAPK genes; time to resistance measured as duration of treatment until resistance observed (e.g., median); phenotypic changes assessed by flow cytometry (markers specified); biomarker profiles assessed by gene expression, mutation profiling and proteomics correlated with response; immune microenvironment features assessed by expression of PD-L1, LAG-3, TIM-3 and cell population percentages; predictive genomic/transcriptomic signatures evaluated for association with MRD negativity."}

Greece

Earliest CTIS Part Ii Submission Date

15-10-2025

Latest Decision Or Authorization Date

20-11-2025

Processing Time Days

36

Number Of Sites

4

Number Of Participants

58

Primary sponsor

Full Name

Hellenic Society Of Hematology

Organisation Type

Patient organisation/association

Country Of Registered Address

Greece

Contract research organisations

Name

Pharmassist Ltd.

Responsibilities

sponsorDuties codes: 1,12,5,8

Name

Diakinisis S.A.

Responsibilities

sponsorDuties codes: 14

Third parties

• {"country":"Greece","full_name":"Diakinisis S.A.","duties_or_roles":"sponsorDuties codes: 14","organisation_type":"Pharmaceutical company"}
• {"country":"Greece","full_name":"Pharmassist Ltd.","duties_or_roles":"sponsorDuties codes: 1,12,5,8","organisation_type":"Pharmaceutical company"}