Clinical trial NCT04174612: AML Patients Bearing FLT3 Mutations Based on Peripheral Blast Clearance
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Acute Myeloid Leukemia With FLT3/ITD Mutation
Lead sponsor: Gruppo Italiano Malattie EMatologiche dell'Adulto
Sponsor class: OTHER
First posted: 2019-11-22
Enrollment: 172
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


Eligibility 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

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.

Primary outcomes:
measure: Event Free Survival
timeFrame: 2,5 years
Secondary outcomes:
measure: Adverse events rate
timeFrame: 2,5 years
measure: Rate of death in aplasia
timeFrame: 2 months
measure: Neutrophil recovery
timeFrame: 2 months
measure: platelet recovery
timeFrame: 2 months
measure: CR rate
timeFrame: 6 months
measure: DFS
timeFrame: 2 years
measure: OS
timeFrame: 2 years
measure: CIR
timeFrame: 2 years
measure: MRD assessment
timeFrame: 6 months
Other outcomes:
Locations:
city: Bari
country: Italy
facility: Aou Consorziale Policlinico - Bari - Uo Ematologia Con Trapianto
city: Bari
country: Italy
facility: Irccs Oncologico Istituto Tumori Giovanni Paolo Ii - Bari - Uo Ematologia
city: Bologna
country: Italy
facility: Aou Di Bologna - Policlinico S. Orsola-Malpighi - Uoc Ematologia
city: Brescia
country: Italy
facility: Asst Degli Spedali Civili Di Brescia - Uo Ematologia
city: Firenze
country: Italy
facility: Aou Careggi- Sod Ematologia
city: Latina
country: Italy
facility: Asl Latina, Presidio Ospedaliero Nord - Ospedale Santa Maria Goretti - Uoc Ematologia
city: Lecce
country: Italy
facility: Asl Lecce, Ospedale 'V. Fazzi' - Uo Ematologia
city: Mestre
country: Italy
facility: Aulss 3 Serenissima, Ospedale Dell'Angelo - Mestre - Uo Ematologia
city: Orbassano
country: Italy
facility: Aou San Luigi Gonzaga - Orbassano - Scdu Ematologia Generale E Oncoematologia
city: Palermo
country: Italy
facility: Ao Ospedali Riuniti Villa Sofia Cervello - Palermo - Uo Ematologia Con Utmo
city: Palermo
country: Italy
facility: Aou Policlinico P. Giaccone - Palermo - Uo Ematologia
city: Pavia
country: Italy
facility: Fondazione Ircss Policlinico San Matteo - Pavia - Uo Ematologia
city: Ravenna
country: Italy
facility: Ausl Della Romagna, Ospedale "Santa Maria Delle Croci" - Ravenna - Ematologia
city: Reggio Calabria
country: Italy
facility: Grande Ospedale Metropolitano "Bianchi-Melacrino-Morelli" Po E. Morelli - Reggio Calabria - Uoc Ematologia
city: Reggio Emilia
country: Italy
facility: Ausl Di Reggio Emilia - Arcispedale Santa Maria Nuova, Irccs - Sc Ematologia
city: Rionero In Vulture
country: Italy
facility: C.R.O.B. - I.R.C.C.S. - Rionero in Volture - Uoc Ematologia
city: Roma
country: Italy
facility: Aou Policlinico Tor Vergata - Roma - Uoc Trapianto Cellule Staminali
city: Siena
country: Italy
facility: Aou Senese - Uoc Ematologia E Trapianti
city: Torino
country: Italy
facility: Aou Città Della Salute E Della Scienza, Ospedale S. Giovanni Battista Molinette - Torino - Sc Ematologia 2
city: Torino
country: Italy
facility: Ospedale Mauriziano Umberto I - Torino - Scdu Ematologia
Study officials:
References: