Acute Myeloid Leukemia (LMA) with FLT3 mutation MedDRA version: 21.1 Level: PT Classification code 10000880 Term: Acute myeloid leukaemia System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 21.1 Level: PT Classification code 10000880 Term: Acute myeloid leukaemia System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: ARACYTIN 500 mg/10 ml Polvere e Solvente per Soluzione Iniettabile
Product Name: Citarabina
Product Code: [NA]
Pharmaceutical Form: Powder and solvent for solution for injection
INN or Pro
Sponsors
FONDAZIONE GIMEMA (GRUPPO ITALIANO MALATTIE EMATOLOGICHE DELL' ADULTO) FRANCO MANDELLI ONLUS
Eligibility
Sex/Gender
All
Inclusion criteria
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. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 100 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 72
Exclusion criteria
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. 4.5. 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. 5.6. Uncontrolled bacterial or fungal infections 6.7. QTc >470 msec on screening ECG (Fridericia’s formula) 7.8. A history of cancer that is not in remission phase following surgery and/or chemotherapy and/or radiotherapy with life expectancy < 1 year. 8.9. 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 |
|---|---|
| Main Objective: The primary objective of the trial is the improvement of outcome measured as event-free 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.;Secondary Objective: 1.Feasibility and safety of PBC-driven treatment, as assessed by: 1-adverse events rate according to CTCAE criteria, 2-rate of death in aplasia, 3-days to neutrophil recovery and 4-days to platelet recovery after induction and consolidation cycles, according to treatment arm 2.Efficacy, in low PBC-patients, of PBC-driven treatment as assessed by: 1-CR rate after first induction cycle, 2-CR rate after two cycles, 3-DFS, 4-OS, 5-CIR and TRM, 6-MRD status, 7- Allogeneic transplant rate in first CR and with active disease 3. Evaluation of outcome for PBC-high patients treated per protocol (standard) and in comparison, with PBC-low treated as per randomization (standard vs experimental), as assessed by: 1-CR rate after first induction cycle, 2-CR rate after two cycles, 3-DFS, 4-OS, 5-Cumulative incidence of relapse (CIR) and Treatment-related mortality (TRM), 6-MRD status, 7- Allogeneic transplant rate in first CR and with active disease;Primary end point(s): The primary endpoint is to evaluate the event-free survival (EFS) at 2 years of an experimental intensified PBC-driven arm in comparison to a standard therapeutic regimen in patients with FLT3+ AML and low peripheral blood clearance (PBC) measured at day 4.;Timepoint(s) of evaluation of this end point: EFS 2 years after treatment in the experimental arm; PBC measured on day 4 compared to day 1. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Feasibility and safety of PBC-driven treatment: 1. Adverse events rate according to CTCAE criteria according to PBC and treatment arm 2. Rate of deaths in aplasia as per ELN 2017 definition according to PBC and treatment arm 3. Days to neutrophils recovery after induction and consolidation cycles according to PBC and treatment arm 4. Days to platelets recovery after induction and consolidation cycles according to PBC and treatment arm 2. Efficacy, in low PBC-patients, of PBC-driven treatment: 1. CR rate as per ELN 2017 definition after first induction cycle according to treatment arm 2. CR rate as per ELN 2017 definition after two cycles according to treatment arm 3. Disease-free survival (DFS) as per ELN 2017 definition according to treatment arm 4. Overall survival (OS) as per ELN 2017 definition according to treatment arm 5. Cumulative incidence of relapse (CIR) and Treatment-related mortality (TRM) according to treatment arm 6. MRD status at pre-defined time-points as per ELN 2017 definition according to treatment arm 7. Actual rate of patients receiving allogeneic transplant in first CR and with active disease according to treatment arm 3. Evaluation of outcome for PBC-high patients treated per protocol (standard) and in comparison, with PBC-low treated as per randomization (standard vs experimental): 1. CR rate as per ELN 2017 definition after first induction cycle according to PBC and treatment arm 2. CR rate as per ELN 2017 definition after two cycles according to PBC and treatment arm 3. Disease-free survival (DFS) as per ELN 2017 definition according to PBC and treatment arm 4. Overall survival (OS) as per ELN 2017 definition according to PBC and treatment arm 5. Cumulative incidence of relapse (CIR) and Treatment-related mortality (TRM) according to PBC and treatment arm 6. MRD status at pre-defined time-points as per ELN 2017 definition according to PBC and treatment arm 7. Actual rate of patients receiving allogeneic transplan | — |
Countries
Italy
Contacts
Public ContactCentro Dati GIMEMA
Fondazione GIMEMA (Gruppo Italiano Malattie EMatologiche dell'Adulto) Franco Mandelli ONLUS
Outcome results
None listed