Clinical trial • Phase III • Haematology

CYTARABINE for Acute myeloid leukaemia (FLT3 mutation)

Phase III trial of CYTARABINE for Acute myeloid leukaemia (FLT3 mutation).

Overview

Trial Therapeutic Area
Haematology
Trial Disease
Acute myeloid leukaemia (FLT3 mutation)
Trial Stage
Phase III
Drug Modality
Small molecule

Key dates

Initial CTIS Submission Date
14-12-2023
First CTIS Authorization Date
12-01-2024

Trial design

Randomised, experimental intensified pbc-driven arm versus standard therapeutic regimen (standard regimen not specified in part i/part ii documents provided).-controlled Phase III trial across 39 sites in Italy.

Randomised
Yes
Comparator
Experimental intensified PBC-driven arm versus standard therapeutic regimen (standard regimen not specified in Part I/Part II documents provided).
Biomarker Stratified
True, Peripheral blast clearance (PBC) measured at day 4; strata: low PBC vs high PBC
Target Sample Size
172

Eligibility

Recruits 172 The trial has vulnerable population selected. Informed consent: "Signed written informed consent according to ICH/EU/GCP and national local laws." Patients with severe neuropsychiatric disorder that impair their ability to understand and sign informed consent are excluded. No procedures for assent or parental consent are described; minimum age is 18..

Pregnancy Exclusion
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.
Vulnerable Population
The trial has vulnerable population selected. Informed consent: "Signed written informed consent according to ICH/EU/GCP and national local laws." Patients with severe neuropsychiatric disorder that impair their ability to understand and sign informed consent are excluded. No procedures for assent or parental consent are described; minimum age is 18.

Inclusion criteria

  • {"criterion_text":"- Patients with de novo AML, untreated, newly diagnosed, according to WHO 2016 criteria\n- Presence of a mutation of FLT3 gene, either ITD and/or TK\n- Adequate availability of diagnostic biologic material for full cytological, cytogenetic, genetic and immunophenotypic disease characterization according to ELN criteria.\n- Presence of morphologically identifiable blasts on peripheral blood at diagnosis\n- Presence of a Leukemia-associated aberrant immune-phenotype (LAIP) as assessed by MFC (multiparametric flow cytometry) at diagnosis\n- Age between 18 and 65 years, included\n- ECOG performance status 0-2 or disease-related reversible ECOG 3 score following adequate supportive care.\n- Signed written informed consent according to ICH/EU/GCP and national local laws."}

Exclusion criteria

  • {"criterion_text":"- Diagnosis of acute promyelocytic leukemia\n- 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\n- Patients with LVEF less than 45% (by echocardiogram or MUGA)\n- 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.\n- 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.\n- Uncontrolled bacterial or fungal infections\n- QTc >470 msec on screening ECG (Fridericia’s formula)\n- A history of cancer that is not in remission phase following surgery and/or chemotherapy and/or radiotherapy with life expectancy < 1 year.\n- 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."}

Endpoints

Primary endpoints

  • {"endpoint_text":"- 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.","definition_or_measurement_approach":"Event-free survival (EFS) at 2 years; low peripheral blood clearance (PBC) is measured at day 4 to identify patients for randomization/assignment."}

Secondary endpoints

  • {"endpoint_text":"- 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","definition_or_measurement_approach":"Safety assessed by adverse events rate per CTCAE; deaths in aplasia per ELN2017; time to neutrophil and platelet recovery after induction/consolidation by PBC and treatment arm."}
  • {"endpoint_text":"- Efficacy, in lowPBC-patients, of PBC-driven treatmentaccording to treatment arm:1.CR rate as perELN2017after1st induction cycle 2.CR rate as perELN2017after2cycles 3.Disease-free surv. as per ELN2017 4.Overall surv. as per ELN2017 5.Cumulative incidence of relapse and Treatment-related mortality 6.MRD at pre-def. time-points as per ELN2017according to PBC and treatment arm 7.Actual rate of patients receiving allogeneic transplant in first CR and with active disease according to PBC and tx arm","definition_or_measurement_approach":"Efficacy endpoints use ELN2017 definitions: CR rates after 1 and 2 induction cycles, DFS and OS per ELN2017, cumulative incidence of relapse and treatment-related mortality, MRD at predefined time points, rate of allo-HSCT in first CR or active disease by arm."}
  • {"endpoint_text":"- Evaluation of outcome for PBC-high patients treated per protocol (standard) and in comparison, with PBC-low treated as per randomization (standard vs experimental), and according to PBC and treatment arm: 1.CRrate as perELN2017after 1°induction cycle 2.CRrate as perELN2017after2cycles 3.DFS as per ELN2017 4.OS as per ELN2017 5.CIR and TRM 6. MRD at defined TPs as per ELN2017 7. actual rate of pz receiving allo HSCT in 1° CR and with active disease","definition_or_measurement_approach":"Outcomes by PBC strata using ELN2017 definitions: CR rates, DFS, OS, cumulative incidence of relapse (CIR), treatment-related mortality (TRM), MRD at defined time points, allo-HSCT rates."}

Recruitment

Planned Sample Size
172
Recruitment Window Months
66
Consent Approach
Signed written informed consent according to ICH/EU/GCP and national local laws is required from participants. Consent is provided by the patient (minimum age 18). Patients unable to understand or sign informed consent due to severe neuropsychiatric disorder are excluded. No mention of assent, parental consent, or language versions is provided in the available documents.

Geography

Total Number Of Sites
39
Total Number Of Participants
172

Italy

Earliest CTIS Part Ii Submission Date
18-05-2023
Latest Decision Or Authorization Date
12-01-2024
Processing Time Days
239
Number Of Sites
39
Number Of Participants
172

Sites

Site Name
Azienda Ospedaliera Ospedali Riuniti Villa Sofia Cervello
Department Name
DIPARTIMENTO DI ONCOLOGIA - UO DI EMATOLOGIA AD INDIRIZZO ONCOLOGICO
Contact Person Name
Antonino Mulè
Site Name
Azienda Ospedaliera Universitaria Citta' Della Salute E Della Scienza Di Torino
Department Name
DIPARTIMENTO DI ONCOLOGIA E EMATOLOGIA - SC EMATOLOGIA +2
Contact Person Name
Ernesta Audisio
Site Name
Azienda USL IRCCS Di Reggio Emilia
Department Name
DIPARTIMENTO ONCOLOGICO E TECNOLOGIE AVANZATE-UO EMATOLOGIA DAY SERVICE
Contact Person Name
Alessia Tieghi
Contact Person Email
alessia.tieghi@ausl.re.it
Site Name
Fondazione IRCCS Policlinico San Matteo
Department Name
DIPARTIMENTO SCIENZE MEDICHE E MALATTIE INFETTIVE-UO EMATOLOGIA
Contact Person Name
Patrizia Zappasodi
Contact Person Email
p.zappasodi@smatteo.pv.it
Site Name
Azienda Ospedale-Universita Padova
Department Name
DIPARTIMENTO DI EMATOLOGIA ED IMMUNOLOGIA CLINICA-UO EMATOLOGIA
Contact Person Name
Carmela Gurrieri
Contact Person Email
carmela.gurrieri@unipd.it
Site Name
Careggi University Hospital
Department Name
DIPARTIMENTO DI MEDICINA SPERIMENTALE E CLINICA - SOD EMATOLOGIA
Contact Person Name
Alessandro Maria Vannucchi
Contact Person Email
aoucareggi@pec.it
Site Name
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Department Name
DIPARTIMENTO DI DIAGNOSTICA PER IMMAGINI, RADIOTERAPIA ONCOLOGICA ED EMATOLOGIA
Contact Person Name
Patrizia Chiusolo
Contact Person Email
patrizia.chiusolo@unicatt.it
Site Name
IRCCS CROB
Department Name
Dipartimento Onco-Ematologico -UOC EMATOLOGIA
Contact Person Name
Giuseppe Pietrantuono
Contact Person Email
giuseppe.pietrantuono@crob.it
Site Name
Istituto Tumori Bari Giovanni Paolo II
Department Name
UO EMATOLOGIA
Contact Person Name
Crescenza Pasciolla
Contact Person Email
c.pasciolla@oncologico.bari.it
Site Name
Grande Ospedale Metropolitano Bianchi Melacrino Morelli
Department Name
Dipartimento Onco-Ematologico -UOC EMATOLOGIA
Contact Person Name
Bruno Marino
Contact Person Email
brunmartin54@gmail.com
Site Name
Azienda Sanitaria Locale Di Salerno
Department Name
EMATOLOGIA
Contact Person Name
Catello Califano
Contact Person Email
c.califano@aslsalerno.it
Site Name
Azienda Unita Sanitaria Locale Di Piacenza
Department Name
Dipartimento Oncologia-Ematologia - UO EMATOLOGIA E CENTRO TRAPIANTI MIDOLLO
Contact Person Name
Lara Pochintesca
Contact Person Email
l.pochintesta@ausc.pc.it
Site Name
Azienda Ospedaliero Universitaria Di Sassari
Department Name
Dipartimento di Medicina Clinica e Sperimentale - UOC EMATOLOGIA
Contact Person Name
Claudio Fozza
Contact Person Email
c.fozza@uniss.it
Site Name
Pia Fondazione Di Culto E Religione Card G Panico
Department Name
Dipartimento Onco-Ematologico -UOC EMATOLOGIA
Contact Person Name
Vincenzo Pavone
Site Name
Fondazione Policlinico Universitario Campus Bio-Medico
Department Name
UOC EMATOLOGIA E TRAPIANTO DI CELLULE STAMINALI
Contact Person Name
Daniele Armiento
Contact Person Email
d.armiento@unicampus.it
Site Name
ULSS3 SERENISSIMA - Ospedale dell'Angelo di Mestre
Department Name
Oncologia Medica
Contact Person Name
Cristina Skert
Site Name
Azienda Ospedaliera Universitaria San Giovanni Di Dio E Ruggi d'Aragona
Department Name
Dipartimento Onco-Ematologico
Contact Person Name
Carmine Selleri
Contact Person Email
cselleri@unisa.it
Site Name
Azienda Ospedaliero-Universitaria Sant Andre
Department Name
Dipartimento Scienze Oncologiche -UOC EMATOLOGIA
Contact Person Name
Agostino Tafuri
Site Name
Azienda Ospedaliera Universitaria Citta' Della Salute E Della Scienza Di Torino (second contact)
Department Name
Dipartimento di Oncologia
Contact Person Name
Luisa Giaccone
Contact Person Email
luisa.giaccone@unito.it
Site Name
ASST Valle Olona
Department Name
Dipartimento Oncologico - SC EMATOLOGIA
Contact Person Name
Fabrizio Ciambelli
Site Name
Ospedale Valduce
Department Name
Dipartimento Medico - UOS EMATOLOGIA
Contact Person Name
Mauro Turrini
Contact Person Email
mturrini@valduce.it
Site Name
Azienda Ospedaliera Policlinico Universitario Tor Vergata
Department Name
Dipartimento di Medicina
Contact Person Name
Adriano Venditti
Contact Person Email
adriano.venditti@unirma2.it
Site Name
Ospedale Vito Fazzi Lecce
Department Name
Polo Oncologico - UO EMATOLOGIA
Contact Person Name
Nicola Di Renzo
Contact Person Email
direnzo.ematolecce@gmail.com
Site Name
Fondazione IRCCS San Gerardo Dei Tintori
Department Name
UO EMATOLOGIA E CTA
Contact Person Name
Monica Fumagalli
Contact Person Email
fumagalli.mo@tiscali.it
Site Name
Azienda Ospedaliera Ordine Mauriziano Di Torino
Department Name
Dipartimento di Scienze Cliniche e Biologiche - SCDU EMATOLOGIA
Contact Person Name
Alessandro Cignetti
Contact Person Email
alessandro.cignetti@unito.it
Site Name
Azienda Ospedaliera Universitaria Policlinico Paolo Giaccone
Department Name
Dipartimento Biomedico di Medicina Interna e Specialistica - UO EMATOLOGIA
Contact Person Name
Sergio Siragusa
Contact Person Email
sergio.siragusa@unipa.it
Site Name
Azienda Socio Sanitaria Territoriale Degli Spedali Civili Di Brescia
Department Name
Dipartimento di Oncologia Clinica
Contact Person Name
Chiara Cattaneo
Site Name
Azienda Ospedaliero-Universitaria Maggiore Della Carita
Department Name
DIMECS E DIPARTIMENTO ONCOLOGICO
Contact Person Name
Monia Lunghi
Contact Person Email
monia.lunghi@med.unipmn.it
Site Name
Istituto Oncologico Veneto
Department Name
Dipartimento di Medicina Clinica 1 - UOC EMATOLOGIA
Contact Person Name
Roberto Sartori
Contact Person Email
roberto.sartori@iov.veneto.it
Site Name
Azienda Ospedaliera Universitaria Senese
Department Name
Dipartimento di Scienze Mediche, Chirurgiche e Neuroscienze - UOC EMATOLOGIA E TRAPIANTI
Contact Person Name
Monica Bocchia
Contact Person Email
bocchia@unisi.it
Site Name
Hospital Santa Maria Della Misericordia
Department Name
EMATOLOGIA E TRAPIANTO MIDOLLO OSSEO
Contact Person Name
Maria Paola Martelli
Contact Person Email
maria.martelli@unipg.it
Site Name
Azienda Sanitaria Locale Di Pescara
Department Name
Dipartimento Oncologico- Ematologico - UOC EMATOLOGIA CLINICA
Contact Person Name
Prassede Salutari
Contact Person Email
prassede.salutari@ausl.pe.it
Site Name
University Hospital Consorziale Policlinico
Department Name
Dipartimento dell'Emergenza e dei Trapianti di Organi (D.E.T.O.)- UO EMATOLOGIA
Contact Person Name
Francesco Albano
Contact Person Email
francesco.albano@uniba.it
Site Name
University Hospital Of Ferrara
Department Name
Dipartimento Oncologico Medico Specialistico
Contact Person Name
Antonio Cuneo
Contact Person Email
cut@unife.it
Site Name
Azienda Ospedaliera Nazionale Ss Antonio E Biagio E C Arrigo Alessandria
Department Name
Dipartimento Internistico - SOC EMATOLOGIA
Contact Person Name
Lorella Depaoli
Contact Person Email
ldepaoli@ospedale.al.it
Site Name
Ospedale Santa Maria Goretti Latina
Department Name
UOC EMATOLOGIA
Contact Person Name
Alessandro Pulsoni
Contact Person Email
alessandro.pulsoni@uniroma1.it
Site Name
Belcolle Hospital
Department Name
Dipartimento Onco-Ematologico -UOC EMATOLOGIA
Contact Person Name
Giulio Trapè
Contact Person Email
giulio.trape@asl.vt.it
Site Name
Azienda Ospedaliero-Universitaria Di Bologna IRCCS Istituto Di Ricerca E Di Cura A Carattere Scientifico
Department Name
Dipartimento di medicina Specialistica, Diagnostica e Sperimentale (DIMES)
Contact Person Name
Antonio Curti
Contact Person Email
antonio.curti2@unibo.it
Site Name
Azienda Unita Sanitaria Locale Della Romagna
Department Name
Dipartimento Onco-Ematologico -UO EMATOLOGIA
Contact Person Name
Michela Rondoni
Contact Person Email
michela.rondoni@auslromagna.it

Sponsor

Primary sponsor

Full Name
Fondazione Gimema Franco Mandelli Onlus
Organisation Type
Health care
Country Of Registered Address
Italy

Third parties

  • {"country":"Italy","full_name":"Laboratorio di Genomica Clinica","duties_or_roles":"code 4","organisation_type":"Health care"}
  • {"country":"Italy","full_name":"Laboratorio CRIMM - Centro di Ricerca e Innovazione delle Malattie Mieloproliferative","duties_or_roles":"code 4","organisation_type":"Health care"}
  • {"country":"Italy","full_name":"Laboratorio di Citofluorimetria, Dipartimento di Diagnostica di Laboratorio","duties_or_roles":"code 4","organisation_type":"Health care"}
  • {"country":"Italy","full_name":"Laboratorio di Diagnostica Integrata Oncoematologica “OPPO”","duties_or_roles":"code 4","organisation_type":"Health care"}

Investigational products

Investigational Product Name
ARACYTIN 500 mg/10 ml Polvere e Solvente per Soluzione Iniettabile
Active Substance
CYTARABINE
Modality
Small molecule
Routes Of Administration
INTRAVENOUS
Route
Intravenous
Authorisation Status
Authorised (marketing authorisation number 022391039 in IT)
Maximum Dose
max daily 3000 mg/m2; max total 9600 mg/m2
Investigational Product Name
MIDOSTAURIN
Active Substance
MIDOSTAURIN
Modality
Small molecule
Routes Of Administration
ORAL
Route
Oral
Authorisation Status
Not specified (marketing authorisation number not provided)
Maximum Dose
max daily 100 mg; max total 1400 mg
Investigational Product Name
DAUNORUBICIN HYDROCHLORIDE
Active Substance
DAUNORUBICIN HYDROCHLORIDE
Modality
Small molecule
Routes Of Administration
INTRAVENOUS INFUSION
Route
Intravenous infusion
Authorisation Status
Not specified (marketing authorisation number not provided)
Maximum Dose
max daily 60 mg/m2; max total 180 mg/m2
Combination Treatment
Yes

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