Gilteritinib for Acute myeloid leukemia (newly diagnosed, FLT3-mutated, non-M3)

Inclusion criteria

• {"criterion_text":"- The patient is ≥ 18 and ≤65 years old.\n- The patient has an Eastern Cooperative Oncology Group (ECOG) performance score (PS) of 0 to 2.\n- The patient has adequate baseline organ function, including cardiac, renal, and hepatic function:a. Left ventricular ejection fraction (LVEF) ≥institutional lower limit of normal as measured by multigated acquisition (MUGA) scan or 2-dimensional (2-D) echocardiography (ECHO) within 21 days before start of therapy and no clinically significant abnormalities on a 12-lead electrocardiogram (ECG). b. ECG: QTcF≤450 male ≤480 female c. Serum creatinine ≤ 1.5 x ULN or an estimated glomerular filtration rate of > 50 mL/min as calculated by the Modification of Diet in Renal Disease equation. d. Bilirubin ≤3 times the upper limit of normal ULN mg/dL except for Gilbert’s condition e. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤3 times the upper limit of normal (ULN)., except if due to leukemic involvement.\n- Patient is positive at diagnosis for FLT3 activating mutation in bone marrow or whole blood.\n- Diagnosis of untreated AML according to WHO 2016, non-APL.\n- If the patient is a woman of childbearing potential (WOCBP), she must have a negative serum or urine pregnancy test at screening within 1 week before treatment.\n- The patient (male and female) agrees to use two acceptable contraceptive methods for the duration of time on the study and continue to use acceptable contraceptive methods for 6 months after the end of treatment\n- The patient has signed informed consent before initiation of any study-specific procedures or treatment.\n- The patient is able to adhere to the study visit schedule and other protocol requirements, including follow-up for survival assessment."}

Exclusion criteria

• {"criterion_text":"- Patient was diagnosed as acute promyelocytic leukemia.\n- Patient has active hepatitis B or C or other active hepatic disorder. Chronic conditions previously cured or in active prophylaxis are allowed in the study\n- Patient has infections, comorbidities or any disease, condition or alteration that per judgment of the investigator may be jeopardized by therapy\n- Patients receiving any other investigational or commercial agents or therapies administered with the intention to treat their malignancy with the exception of Hydroxyurea (HU) or 6- Mercaptopurine (6MP) in patients who need to continue this agent to maintain WBC count ≤10,000/mm3. HU and 6MP must be discontinued at the time of initiation of study medications.\n- Patient has BCR-ABL-positive leukemia or chronic myelogenous leukemia in blast crisis.\n- Patient has clinically active central nervous system leukemia.\n- Patient has been diagnosed with another malignancy, unless disease-free for at least 3 years. Subjects with treated nonmelanoma skin cancer, in situ carcinoma or cervical intraepithelial neoplasia, papillary thyroid carcinoma, regardless of the disease-free duration, are eligible for this study if definitive treatment for the condition has been completed. Subjects with organconfined prostate cancer with no evidence of recurrent or progressive disease are eligible if hormonal therapy has been initiated or the malignancy has been surgically removed or treated with definitive radiotherapy.\n- Patient has had major surgery within 4 weeks prior to the first study dose.\n- Patient has radiation therapy within 4 weeks prior to the first study dose.\n- Patient has congestive heart failure New York Heart Association (NYHA) class 3 or 4 or patient with a history of congestive heart failure NYHA class 3 or 4 in the past, unless a screening echocardiogram performed within 1 month prior to study entry results in a left ventricular ejection fraction that is ≥ 45%.\n- Patient has an active uncontrolled infection.\n- Patient has active human immunodeficiency virus infection."}

Primary endpoints

• {"endpoint_text":"- Primary end point is the rate of CR after course 1 or course 2 if course 2 is administered (CR + CRi + CRp).","definition_or_measurement_approach":"Rate of complete remission (CR + CRi + CRp) measured after course 1 or after course 2 if course 2 is administered."}

Secondary endpoints

• {"endpoint_text":"- Percentage of MRD negative CR (flow cytometry) after cycle 1, 2, consolidation, End of Treatment and follow-up (centralized analysis).\n- To Describe duration of MRD negative CR measured as the time from achievement of MRD negative CR to MRD positive test, relapse or death for any cause.\n- To Describe PFS, measured as the time from 1st day of administration of study treatment to progression or death for any cause.\n- To Describe OS, measured as the time from 1st day of administration of study treatment to death for any cause.\n- To Describe the proportion of patients who proceed to HSCT in MRD negative CR.\n- To Describe the incidence of AE.\n- To Analyze incidence and type of whole gene FLT3 mutations.\n- To Analyze the overlap between conventional MRD and MRD with next generation technologies (NGS) for correlative purposes.\n- To Describe adherence to treatment.\n- To Describe quality of life.","definition_or_measurement_approach":"Percentage of MRD-negative CR assessed by flow cytometry at specified timepoints (cycle 1, 2, consolidation, EOT, follow-up) - centralized analysis; Duration of MRD-negative CR measured as time from MRD-negative CR to MRD positivity, relapse, or death; PFS measured from first day of study treatment to progression or death; OS measured from first day of study treatment to death; proportion proceeding to HSCT assessed among patients in MRD-negative CR; incidence of AEs collected/reported per protocol; analysis of whole gene FLT3 mutation incidence and type; comparison/overlap between conventional MRD and NGS MRD methods for correlative analyses; adherence described per protocol measures; quality of life described per protocol assessments."}

Italy

Earliest CTIS Part Ii Submission Date

11-06-2025

Latest Decision Or Authorization Date

10-02-2026

Processing Time Days

244

Number Of Sites

22

Number Of Participants

80

Primary sponsor

Full Name

Fondazione Gimema Franco Mandelli Onlus

Organisation Type

Patient organisation/association

Country Of Registered Address

Italy

Third parties

• {"email":"clinical-research@evidenze.com","country":"Italy","full_name":"Evidenze Health S.r.l.","duties_or_roles":"sponsorDuties codes: [1]","organisation_type":"Pharmaceutical company"}
• {"email":"giorgia.simonetti@irst.emr.it","country":"Italy","full_name":"Istituto Romagnolo Per Lo Studio Dei Tumori Dino Amadori IRST S.r.l.","duties_or_roles":"sponsorDuties codes: [4]","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"email":"enrico.carminati@hsanmartino.it","country":"Italy","full_name":"IRCCS Ospedale Policlinico San Martino","duties_or_roles":"sponsorDuties codes: [4]","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"email":"elisabetta.tedone@hsanmartino.it","country":"Italy","full_name":"IRCCS Ospedale Policlinico San Martino","duties_or_roles":"sponsorDuties codes: [4]","organisation_type":"Hospital/Clinic/Other health care facility"}