Acute Myeloid Leukemia With FLT3/ITD Mutation
Conditions
Brief summary
Prospective, multi-center, interventional, randomized, open clinical trial for the treatment of acute myeloid leukemia with FLT3 mutations customized upon the prognostic parameter PBC
Interventions
DRUGCytarabine
100 mg/m2/bid day 1-3 100 mg/m2/die day 4-7
DRUGDaunorubicin
60 mg/m2/die day 1-3
DRUGMidostaurin
50 mg/bid day 8-21
DRUGCytarabine HD
100 mg/m2/bid day 1-3 100 mg/m2/die day 4 1.500 mg bid day 5-7
Sponsors
Gruppo Italiano Malattie EMatologiche dell'Adulto
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. Patients with de novo AML, untreated, newly diagnosed, according to WHO 2016 criteria 2. Presence of a mutation of FLT3 gene, either ITD and/or TKD 3. Adequate availability of diagnostic biologic material for full cytological, cytogenetic, genetic and immunophenotypic disease characterization according to ELN criteria. 4. Presence of morphologically identifiable blasts on peripheral blood at diagnosis 5. Presence of a Leukemia-associated aberrant immune-phenotype (LAIP) as assessed by MFC (multiparametric flow cytometry) at diagnosis 6. Age between 18 and 65 years, included 7. ECOG performance status 0-2 or disease-related reversible ECOG 3 score following adequate supportive care. 8. Signed written informed consent according to ICH/EU/GCP and national local laws
Exclusion criteria
1. Diagnosis of acute promyelocytic leukemia 2. 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 3. Patients with LVEF less than 45% (by echocardiogram or MUGA) 4. 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. 5. Uncontrolled bacterial or fungal infections 6. QTc \>470 msec on screening ECG (Fridericia's formula) 7. A history of cancer that is not in remission phase following surgery and/or chemotherapy and/or radiotherapy with life expectancy \< 1 year. 8. 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Event Free Survival | 2,5 years | Improvement of outcome measured as event-free survival (EFS) in patients with FLT3+ acute myeloid leukemia who are predicted to have low chemosensitivity, as defined upon the biomarker peripheral blast clearance (PBC), following the application of an early intensification of overall treatment, both in induction (high-doses delivery) and in consolidation (allocation to allogeneic transplant) phase, compared with standard regimens |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Rate of death in aplasia | 2 months | rate of death in aplasia |
| Neutrophil recovery | 2 months | Median number of days for neutrophil recovery |
| platelet recovery | 2 months | Median number of days for platelet recovery |
| CR rate | 6 months | Complete remission rate after induction |
| Adverse events rate | 2,5 years | Adverse events rate according to CTCAE criteria |
| OS | 2 years | Overall survival |
| CIR | 2 years | Cumulative incidence of relapse |
| MRD assessment | 6 months | MRD negativity rate at the end of induction and consolidation |
| DFS | 2 years | Disease-free survival |
Countries
Italy
Contacts
Primary ContactPaola Fazi
Backup ContactEnrico Crea
Outcome results
None listed