Acute Myeloid Leukemia With FLT3/ITD MutationPhase 3AMELIORATENCT04174612
AML Patients Bearing FLT3 Mutations Based on Peripheral Blast Clearance
A Phase 3 study testing Cytarabine, Daunorubicin and Midostaurin in people with Acute Myeloid Leukemia With FLT3/ITD Mutation, run by Gruppo Italiano Malattie EMatologiche dell'Adulto at 20 sites in Italy.
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 Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Acute Myeloid Leukemia With FLT3/ITD Mutation
- What is being tested?
- Cytarabine, Daunorubicin and Midostaurin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 172 participants
- Where
- 20 sitesItaly
- Study dates
- 24 Apr 2020to 1 Aug 2025
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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.
Trial locations and contacts
20 sites in 1 country.
20 sites in 1 country
Italy20 sites, 20 recruiting
- Recruiting
Aou Consorziale Policlinico - Bari - Uo Ematologia Con Trapianto
Bari
Francesco Albano, francesco.albano@uniba.it
- Recruiting
Irccs Oncologico Istituto Tumori Giovanni Paolo Ii - Bari - Uo Ematologia
Bari
Crescenza Pasciolla, c.pasciolla@oncologico.bari.it
- Recruiting
Aou Di Bologna - Policlinico S. Orsola-Malpighi - Uoc Ematologia
Bologna
Antonio Curti, antonio.curti2@unibo.it
- Recruiting
Asst Degli Spedali Civili Di Brescia - Uo Ematologia
Brescia
Chiara Cattaneo, chiara.cattaneo@libero.it
- Recruiting
Aou Careggi- Sod Ematologia
Florence
Vannucchi
Alessandro Vannucchi
- Recruiting
Asl Latina, Presidio Ospedaliero Nord - Ospedale Santa Maria Goretti - Uoc Ematologia
Latina
Giuseppe U Cimino, 3495378159, cimino@bce.uniroma1.it
- Recruiting
Asl Lecce, Ospedale 'V. Fazzi' - Uo Ematologia
Lecce
Nicola Di Renzo, 3388178577, direnzo.ematolecce@gmail.com
- Recruiting
Aulss 3 Serenissima, Ospedale Dell'Angelo - Mestre - Uo Ematologia
Mestre
Renato Bassan, 3398508691, Renato.Bassan@aulss3.veneto.it
- Recruiting
Aou San Luigi Gonzaga - Orbassano - Scdu Ematologia Generale E Oncoematologia
Orbassano
Daniela E Cilloni, 3332818086, daniela.cilloni@unito.it
- Recruiting
Ao Ospedali Riuniti Villa Sofia Cervello - Palermo - Uo Ematologia Con Utmo
Palermo
Antonino C Mulè, a.mule@villasofia.it
- Recruiting
Aou Policlinico P. Giaccone - Palermo - Uo Ematologia
Palermo
Maria Enza U Mitra, memitra@yahoo.com
- Recruiting
Fondazione Ircss Policlinico San Matteo - Pavia - Uo Ematologia
Pavia
Patrizia U Zappasodi, p.zappasodi@smatteo.pv.it
- Recruiting
Ausl Della Romagna, Ospedale "Santa Maria Delle Croci" - Ravenna - Ematologia
Ravenna
Michela Rondoni, michela.rondoni@auslromagna.it
- Recruiting
Grande Ospedale Metropolitano "Bianchi-Melacrino-Morelli" Po E. Morelli - Reggio Calabria - Uoc Ematologia
Reggio Calabria
Bruno Marino Martino, 3489335096, brunmartin54@gmail.com
- Recruiting
Ausl Di Reggio Emilia - Arcispedale Santa Maria Nuova, Irccs - Sc Ematologia
Reggio Emilia
Alessia S Tieghi, alessia.tieghi@ausl.re.it
- Recruiting
C.R.O.B. - I.R.C.C.S. - Rionero in Volture - Uoc Ematologia
Rionero in Vulture
Giuseppe U Pietrantuono, giuseppe.pietrantuono@crob.it
- Recruiting
Aou Policlinico Tor Vergata - Roma - Uoc Trapianto Cellule Staminali
Roma
Adriano Venditti, adriano.venditti@uniroma2.it
- Recruiting
Aou Senese - Uoc Ematologia E Trapianti
Siena
Monica Bocchia, bocchia@unisi.it
- Recruiting
Aou Città Della Salute E Della Scienza, Ospedale S. Giovanni Battista Molinette - Torino - Sc Ematologia 2
Torino
Ernesta E Audisio, eaudisio@cittadellasalute.to.it
- Recruiting
Ospedale Mauriziano Umberto I - Torino - Scdu Ematologia
Torino
Alessandro Cignetti, alessandro.cignetti@unito.it
About this study
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
Prospective, multi-center, interventional, randomized, open clinical trial for the treatment of acute myeloid leukemia with FLT3 mutations customized upon the prognostic parameter PBC
- Being tested
- Cytarabine, Daunorubicin, Midostaurin, Cytarabine HD
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CytarabineDrug
100 mg/m2/bid day 1-3 100 mg/m2/die day 4-7
DaunorubicinDrug
60 mg/m2/die day 1-3
MidostaurinDrug
50 mg/bid day 8-21
Cytarabine HDDrug
100 mg/m2/bid day 1-3 100 mg/m2/die day 4 1.500 mg bid day 5-7
| Study group | Role | What they receive |
|---|---|---|
| Standard clinical treatment | Active comparator | Patients will complete "3+7" + Midostaurin induction course. Receives: 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 Receives: Drug: Daunorubicin; Drug: Midostaurin; Drug: Cytarabine HD |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 2,5 years
Secondary outcomes (9)
Adverse events rate
Adverse events rate according to CTCAE criteria
Measured: 2,5 years
Rate of death in aplasia
rate of death in aplasia
Measured: 2 months
Neutrophil recovery
Median number of days for neutrophil recovery
Measured: 2 months
platelet recovery
Median number of days for platelet recovery
Measured: 2 months
CR rate
Complete remission rate after induction
Measured: 6 months
DFS
Disease-free survival
Measured: 2 years
OS
Overall survival
Measured: 2 years
CIR
Cumulative incidence of relapse
Measured: 2 years
MRD assessment
MRD negativity rate at the end of induction and consolidation
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Nov 2019
- Study start24 Apr 2020
- Primary completionDec 2022 (estimated)
- Study completion1 Aug 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Myeloid Leukemia With FLT3/ITD MutationStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 172 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Gruppo Italiano Malattie EMatologiche dell'Adulto
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04174612
- Sponsor's protocol ID
- AML1919
- Acronym
- AMELIORATE
- Status last verified
- Mar 2022
- First submitted
- 11 Nov 2019
- Last updated
- 2 Mar 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Mar 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04174612
- Acronym / sponsor ID
- AMELIORATE / AML1919
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 172 participants (estimated)
- Lead sponsor
- Gruppo Italiano Malattie EMatologiche dell'AdultoUniversity, hospital or other
- Study start
- 24 Apr 2020 (actual)
- Primary completion
- Dec 2022 (estimated)
- Study completion
- 1 Aug 2025 (estimated)
- First posted
- 22 Nov 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Prospective, multi-center, interventional, randomized, open clinical trial for the treatment of acute myeloid leukemia with FLT3 mutations customized upon the prognostic parameter PBC
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Standard clinical treatment | Active comparator | Drug: Cytarabine, Drug: Daunorubicin, Drug: MidostaurinPatients will complete "3+7" + Midostaurin induction course. |
| Experimental treatment | Experimental | Drug: Daunorubicin, Drug: Midostaurin, Drug: Cytarabine HDThe 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 |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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
Key exclusion criteria (8 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Cytarabine100 mg/m2/bid day 1-3 100 mg/m2/die day 4-7 | Drug | Standard clinical treatment |
| Daunorubicin60 mg/m2/die day 1-3 | Drug | Experimental treatment, Standard clinical treatment |
| Midostaurin50 mg/bid day 8-21 | Drug | Experimental treatment, Standard clinical treatment |
| Cytarabine HD100 mg/m2/bid day 1-3 100 mg/m2/die day 4 1.500 mg bid day 5-7 | Drug | Experimental treatment |
Primary outcome
Event Free Survival
Time frame: 2,5 years
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
9 secondary outcomes
Adverse events rate
Time frame: 2,5 years
Rate of death in aplasia
Time frame: 2 months
Neutrophil recovery
Time frame: 2 months
platelet recovery
Time frame: 2 months
CR rate
Time frame: 6 months
DFS
Time frame: 2 years
OS
Time frame: 2 years
CIR
Time frame: 2 years
MRD assessment
Time frame: 6 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Mar 2022.
Related trials for Acute Myeloid Leukemia With FLT3/ITD Mutation
Not yet recruitingPhase 2
Testing the Investigational Medication Combination of Azacitidine, Venetoclax, and Quizartinib Compared to the Usual Treatment of Cytarabine, Daunorubicin, and Quizartinib for Patients With FLT3-ITD Mutant Acute Myeloid Leukemia (A MyeloMATCH Treatment Trial)
Acute Myeloid Leukemia
RecruitingPhase 2
Evaluation of Two Dose Levels of Quizartinib as Maintenance in FLT3-ITD (+) Acute Myeloid Leukemia Patients in Complete Remission
Acute Myeloid Leukemia, Leukemia
Active, not recruitingPhase 3
Quizartinib or Placebo Plus Chemotherapy in Newly Diagnosed Patients With FLT3-ITD Negative AML
Leukemia
RecruitingPhase 1
SNDX-5613 and Gilteritinib for the Treatment of Relapsed or Refractory FLT3-Mutated Acute Myeloid Leukemia and Concurrent MLL-Rearrangement or NPM1 Mutation
Acute Myeloid Leukemia With FLT3/ITD Mutation, Acute Myeloid Leukemia With KMT2A Rearrangement
Active, not recruitingPhase 1/2
Safety and Efficacy of Quizartinib in Children and Young Adults With Acute Myeloid Leukemia (AML), a Cancer of the Blood
Acute Myeloid Leukemia
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
20 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Cytarabine, Daunorubicin and Midostaurin in people with Acute Myeloid Leukemia With FLT3/ITD Mutation, run by Gruppo Italiano Malattie EMatologiche dell'Adulto at 20 sites in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 2 Mar 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 20 sites in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Paola Fazi (0670390528, p.fazi@gimema.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Event Free Survival (time frame: 2,5 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Mar 2022.