AML Patients Bearing FLT3 Mutations Based on Peripheral Blast Clearance

NCT04174612 | Unknown Phase 3 DMC

• 1 other identifier: AML1919
• Study Type: interventional
• Target: 172
• Locations: 1 country
• Sites: 20

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

Conditions

Acute Myeloid Leukemia With FLT3/ITD Mutation

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (9)

• Adverse events rate

  2,5 years

• Rate of death in aplasia

  2 months

• Neutrophil recovery

  2 months

• platelet recovery

  2 months

• CR rate

  6 months

Study Arms (2)

Standard clinical treatment

ACTIVE COMPARATOR

Patients will complete "3+7" + Midostaurin induction course.

Drug: Cytarabine; Drug: Daunorubicin; Drug: Midostaurin

Experimental treatment

EXPERIMENTAL

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

Drug: Daunorubicin; Drug: Midostaurin; Drug: Cytarabine HD

Interventions

Cytarabine DRUG

100 mg/m2/bid day 1-3 100 mg/m2/die day 4-7

Standard clinical treatment

Daunorubicin DRUG

60 mg/m2/die day 1-3

Experimental treatment; Standard clinical treatment

Midostaurin DRUG

50 mg/bid day 8-21

Experimental treatment; Standard clinical treatment

Cytarabine HD DRUG

100 mg/m2/bid day 1-3 100 mg/m2/die day 4 1.500 mg bid day 5-7

Experimental treatment

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Gruppo Italiano Malattie EMatologiche dell'Adulto: lead

Study Sites (20)

Aou Consorziale Policlinico - Bari - Uo Ematologia Con Trapianto

Bari, Italy

RECRUITING

Irccs Oncologico Istituto Tumori Giovanni Paolo Ii - Bari - Uo Ematologia

Bari, Italy

RECRUITING

Aou Di Bologna - Policlinico S. Orsola-Malpighi - Uoc Ematologia

Bologna, Italy

RECRUITING

Asst Degli Spedali Civili Di Brescia - Uo Ematologia

Brescia, Italy

RECRUITING

Aou Careggi- Sod Ematologia

Florence, Italy

RECRUITING

Asl Latina, Presidio Ospedaliero Nord - Ospedale Santa Maria Goretti - Uoc Ematologia

Latina, Italy

RECRUITING

Asl Lecce, Ospedale 'V. Fazzi' - Uo Ematologia

Lecce, Italy

RECRUITING

Aulss 3 Serenissima, Ospedale Dell'Angelo - Mestre - Uo Ematologia

Mestre, Italy

RECRUITING

Aou San Luigi Gonzaga - Orbassano - Scdu Ematologia Generale E Oncoematologia

Orbassano, Italy

RECRUITING

Ao Ospedali Riuniti Villa Sofia Cervello - Palermo - Uo Ematologia Con Utmo

Palermo, Italy

RECRUITING

Aou Policlinico P. Giaccone - Palermo - Uo Ematologia

Palermo, Italy

RECRUITING

Fondazione Ircss Policlinico San Matteo - Pavia - Uo Ematologia

Pavia, Italy

RECRUITING

Ausl Della Romagna, Ospedale "Santa Maria Delle Croci" - Ravenna - Ematologia

Ravenna, Italy

RECRUITING

Grande Ospedale Metropolitano "Bianchi-Melacrino-Morelli" Po E. Morelli - Reggio Calabria - Uoc Ematologia

Reggio Calabria, Italy

RECRUITING

Ausl Di Reggio Emilia - Arcispedale Santa Maria Nuova, Irccs - Sc Ematologia

Reggio Emilia, Italy

RECRUITING

C.R.O.B. - I.R.C.C.S. - Rionero in Volture - Uoc Ematologia

Rionero in Vulture, Italy

RECRUITING

Aou Policlinico Tor Vergata - Roma - Uoc Trapianto Cellule Staminali

Roma, Italy

RECRUITING

Aou Senese - Uoc Ematologia E Trapianti

Siena, Italy

RECRUITING

Aou Città Della Salute E Della Scienza, Ospedale S. Giovanni Battista Molinette - Torino - Sc Ematologia 2

Torino, Italy

RECRUITING

Ospedale Mauriziano Umberto I - Torino - Scdu Ematologia

Torino, Italy

RECRUITING

MeSH Terms

Interventions

Cytarabine; Daunorubicin; midostaurin

Intervention Hierarchy (Ancestors)

Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates

Central Study Contacts

Paola Fazi

CONTACT

0670390528; p.fazi@gimema.it

Enrico Crea

CONTACT

0670390514; e.crea@gimema.it

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 11, 2019
• First Posted: November 22, 2019
• Study Start: April 24, 2020
• Primary Completion: December 1, 2022
• Study Completion: August 1, 2025
• Last Updated: March 2, 2022

Record last verified: 2022-03

Locations

IT (20)