Study to identify the most appropriate therapy for patients with Acute Myeloid Leukemia carrying FLT3 mutation, using the PBC biomarker to customize therapy.

Trial details

Who runs it

Fondazione G.I.M.Em.A Franco Mandelli Ets

Trial code

NCT04174612EU 2023-505901-17-00

Record updated

19 October 2026

Original description

The primary objective of the trial is the improvement of outcome measured as eventfree survival (EFS) in patients with FLT3+ acute myeloid leukemia who are predicted to have low chemosensitivity, by the measurement of “peripheral blast clearance (PBC)”, following the application of an early intensification of treatment, both in induction (high-doses delivery) and in consolidation (allocation to allogeneic transplant) phase, compared with standard regimens.Read full original descriptionShow less

A Phase 3, prospective, randomized, multi-center, intervention trial of early intensification in AML patients bearing FLT3 mutations based on peripheral blast clearance. A MYNERVA-GIMEMA study. AMELIORATE (AML Early IntensificatiOn based on peRipheral blAsT clEarance). AML1919

The primary objective of the trial is the improvement of outcome measured as eventfree survival (EFS) in patients with FLT3+ acute myeloid leukemia who are predicted to have low chemosensitivity, by the measurement of “peripheral blast clearance (PBC)”, following the application of an early intensification of treatment, both in induction (high-doses delivery) and in consolidation (allocation to allogeneic transplant) phase, compared with standard regimens.

Inclusion: Patients with de novo AML, untreated, newly diagnosed, according to WHO 2016 criteria; Presence of a mutation of FLT3 gene, either ITD and/or TK; Adequate availability of diagnostic biologic material for full cytological, cytogenetic, genetic and immunophenotypic disease characterization according to ELN criteria; Presence of morphologically identifiable blasts on peripheral blood at diagnosis; Presence of a Leukemia-associated aberrant immune-phenotype (LAIP) as assessed by MFC (multiparametric flow cytometry) at diagnosis; Age between 18 and 65 years, included; ECOG performance status 0-2 or disease-related reversible ECOG 3 score following adequate supportive care; Signed written informed consent according to ICH/EU/GCP and national local laws.

Exclusion: Pre-existing HIV positive serology (i.e. already known before enrolment). The participation to the study will require serology testing for HIV positivity at baseline: in case of HIV positivity or refusal to perform HIV testing, the patient will be considered not eligible; Uncontrolled bacterial or fungal infections; A history of cancer that is not in remission phase following surgery and/or chemotherapy and/or radiotherapy with life expectancy < 1 year; Patients with LVEF less than 45% (by echocardiogram or MUGA); Pre-existing, uncontrolled pathology such as heart failure (congestive/ischaemic, acute myocardial infarction within the post 3 months, untreatable arrhythmias, NYHA classes III and IV), sever liver disease with total bilirubin =2,5 x ULN and/or ALT>3 ULN (unless attributable to AML), acute or chronic pancreatitis, kidney function impairment with serum creatinine =2,5 (unless attributable to AML) and severe neuropsychiatric disorder that impairs the patient’s ability to understand and sign the informed consent or to cope with the intended treatment plan. For altered liver, pancreas and kidney function tests, eligibility criteria can be reassessed at 24-96 hours, following the institution of adequate supportive measures; QTc >470 msec on screening ECG (Fridericia’s formula); Diagnosis of acute promyelocytic leukemia; Diagnosis of AML with t(8;21)(q22:q22)/RUNX1-RUNX1T1 and t(16;16)(p13:q22) or inversion of chromosome 16 (16)(p13q22)/CBFB-MYH11; in case of suspicion of CBF-related AML due to morphological and/or immunophenotypic features, specific FISH or molecular testing is strongly recommended in accordance with WHO criteria3,157; Pregnancy declared by the patient herself. A pregnancy test is performed at diagnosis and, if applicable, before allogeneic HSCT. Female and male patients who are fertile must agree to use an effective form of contraception with their sexual partners from enrollment through 4 months after the end of treatment.

ClinicalTrials.gov NCT04174612 · EU CTIS 2023-505901-17-00