AML Patients Bearing FLT3 Mutations Based on Peripheral Blast Clearance

Acute Myeloid Leukemia With FLT3/ITD Mutation Clinical Trial

— AMELIORATE  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04174612
• Other study ID #: AML1919
• Status: Recruiting
• Phase: Phase 3
• Start date: April 24, 2020
• Est. completion date: August 1, 2025

Study information

• Verified date: March 2022
• Source: Gruppo Italiano Malattie EMatologiche dell'Adulto
• Contact: Paola Fazi
• Phone: 0670390528
• Email: p.fazi[@]gimema.it
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 172
• Est. completion date: August 1, 2025
• Est. primary completion date: December 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Acute Myeloid Leukemia With FLT3/ITD Mutation

Intervention

Drug:
• Cytarabine
100 mg/m2/bid day 1-3 100 mg/m2/die day 4-7
• Daunorubicin
60 mg/m2/die day 1-3
• Midostaurin
50 mg/bid day 8-21
• Cytarabine HD
100 mg/m2/bid day 1-3 100 mg/m2/die day 4 1.500 mg bid day 5-7

Locations

Country	Name	City	State
Italy	Aou Consorziale Policlinico - Bari - Uo Ematologia Con Trapianto	Bari
Italy	Irccs Oncologico Istituto Tumori Giovanni Paolo Ii - Bari - Uo Ematologia	Bari
Italy	Aou Di Bologna - Policlinico S. Orsola-Malpighi - Uoc Ematologia	Bologna
Italy	Asst Degli Spedali Civili Di Brescia - Uo Ematologia	Brescia
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	Aulss 3 Serenissima, Ospedale Dell'Angelo - Mestre - Uo Ematologia	Mestre
Italy	Aou San Luigi Gonzaga - Orbassano - Scdu Ematologia Generale E Oncoematologia	Orbassano
Italy	Ao Ospedali Riuniti Villa Sofia Cervello - Palermo - Uo Ematologia Con Utmo	Palermo
Italy	Aou Policlinico P. Giaccone - Palermo - Uo Ematologia	Palermo
Italy	Fondazione Ircss Policlinico San Matteo - Pavia - Uo Ematologia	Pavia
Italy	Ausl Della Romagna, Ospedale "Santa Maria Delle Croci" - Ravenna - Ematologia	Ravenna
Italy	Grande Ospedale Metropolitano "Bianchi-Melacrino-Morelli" Po E. Morelli - Reggio Calabria - Uoc Ematologia	Reggio Calabria
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	Aou Policlinico Tor Vergata - Roma - Uoc Trapianto Cellule Staminali	Roma
Italy	Aou Senese - Uoc Ematologia E Trapianti	Siena
Italy	Aou Città Della Salute E Della Scienza, Ospedale S. Giovanni Battista Molinette - Torino - Sc Ematologia 2	Torino
Italy	Ospedale Mauriziano Umberto I - Torino - Scdu Ematologia	Torino

Sponsors (1)

Lead Sponsor	Collaborator
Gruppo Italiano Malattie EMatologiche dell'Adulto

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Event Free Survival	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	2,5 years
Secondary	Adverse events rate	Adverse events rate according to CTCAE criteria	2,5 years
Secondary	Rate of death in aplasia	rate of death in aplasia	2 months
Secondary	Neutrophil recovery	Median number of days for neutrophil recovery	2 months
Secondary	platelet recovery	Median number of days for platelet recovery	2 months
Secondary	CR rate	Complete remission rate after induction	6 months
Secondary	DFS	Disease-free survival	2 years
Secondary	OS	Overall survival	2 years
Secondary	CIR	Cumulative incidence of relapse	2 years
Secondary	MRD assessment	MRD negativity rate at the end of induction and consolidation	6 months