AML Patients Bearing FLT3 Mutations Based on Peripheral Blast Clearance
- Conditions
- Acute Myeloid Leukemia With FLT3/ITD Mutation
- Interventions
- Registration Number
- NCT04174612
- 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
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 172
- Patients with de novo AML, untreated, newly diagnosed, according to WHO 2016 criteria
- Presence of a mutation of FLT3 gene, either ITD and/or TKD
- 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
- 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
- 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.
- Uncontrolled bacterial or fungal infections
- QTc >470 msec on screening ECG (Fridericia's formula)
- A history of cancer that is not in remission phase following surgery and/or chemotherapy and/or radiotherapy with life expectancy < 1 year.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Standard clinical treatment Daunorubicin Patients will complete "3+7" + Midostaurin induction course. Standard clinical treatment Midostaurin Patients will complete "3+7" + Midostaurin induction course. Experimental treatment Daunorubicin The experimental arm will provide 2 main modifications compared to standard: i) immediate switch to intensified induction with high-doses Cytarabine (on days 5, 6 and 7 of induction) ii) early allocation to high-risk disease category to be refined according to ELN stratification and post induction MRD status Experimental treatment Cytarabine HD The experimental arm will provide 2 main modifications compared to standard: i) immediate switch to intensified induction with high-doses Cytarabine (on days 5, 6 and 7 of induction) ii) early allocation to high-risk disease category to be refined according to ELN stratification and post induction MRD status Standard clinical treatment Cytarabine Patients will complete "3+7" + Midostaurin induction course. Experimental treatment Midostaurin The experimental arm will provide 2 main modifications compared to standard: i) immediate switch to intensified induction with high-doses Cytarabine (on days 5, 6 and 7 of induction) ii) early allocation to high-risk disease category to be refined according to ELN stratification and post induction MRD status
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method DFS 2 years Disease-free survival
Adverse events rate 2,5 years Adverse events rate according to CTCAE criteria
Rate of death in aplasia 2 months rate of death in aplasia
Neutrophil recovery 2 months Median number of days for neutrophil recovery
CR rate 6 months Complete remission rate after induction
OS 2 years Overall survival
platelet recovery 2 months Median number of days for platelet recovery
CIR 2 years Cumulative incidence of relapse
MRD assessment 6 months MRD negativity rate at the end of induction and consolidation
Trial Locations
- Locations (20)
Aou San Luigi Gonzaga - Orbassano - Scdu Ematologia Generale E Oncoematologia
🇮🇹Orbassano, Italy
Aulss 3 Serenissima, Ospedale Dell'Angelo - Mestre - Uo Ematologia
🇮🇹Mestre, Italy
Aou Policlinico P. Giaccone - Palermo - Uo Ematologia
🇮🇹Palermo, Italy
Fondazione Ircss Policlinico San Matteo - Pavia - Uo Ematologia
🇮🇹Pavia, Italy
Asst Degli Spedali Civili Di Brescia - Uo Ematologia
🇮🇹Brescia, Italy
Ao Ospedali Riuniti Villa Sofia Cervello - Palermo - Uo Ematologia Con Utmo
🇮🇹Palermo, Italy
Aou Policlinico Tor Vergata - Roma - Uoc Trapianto Cellule Staminali
🇮🇹Roma, Italy
Aou Città Della Salute E Della Scienza, Ospedale S. Giovanni Battista Molinette - Torino - Sc Ematologia 2
🇮🇹Torino, Italy
Aou Careggi- Sod Ematologia
🇮🇹Firenze, Italy
Asl Latina, Presidio Ospedaliero Nord - Ospedale Santa Maria Goretti - Uoc Ematologia
🇮🇹Latina, Italy
Asl Lecce, Ospedale 'V. Fazzi' - Uo Ematologia
🇮🇹Lecce, Italy
Aou Senese - Uoc Ematologia E Trapianti
🇮🇹Siena, Italy
Ausl Della Romagna, Ospedale "Santa Maria Delle Croci" - Ravenna - Ematologia
🇮🇹Ravenna, Italy
Ausl Di Reggio Emilia - Arcispedale Santa Maria Nuova, Irccs - Sc Ematologia
🇮🇹Reggio Emilia, Italy
C.R.O.B. - I.R.C.C.S. - Rionero in Volture - Uoc Ematologia
🇮🇹Rionero In Vulture, Italy
Ospedale Mauriziano Umberto I - Torino - Scdu Ematologia
🇮🇹Torino, Italy
Irccs Oncologico Istituto Tumori Giovanni Paolo Ii - Bari - Uo Ematologia
🇮🇹Bari, Italy
Aou Consorziale Policlinico - Bari - Uo Ematologia Con Trapianto
🇮🇹Bari, Italy
Aou Di Bologna - Policlinico S. Orsola-Malpighi - Uoc Ematologia
🇮🇹Bologna, Italy
Grande Ospedale Metropolitano "Bianchi-Melacrino-Morelli" Po E. Morelli - Reggio Calabria - Uoc Ematologia
🇮🇹Reggio Calabria, Italy