AML Patients Bearing FLT3 Mutations Based on Peripheral Blast Clearance (AMELIORATE)

March 1, 2022 updated by: Gruppo Italiano Malattie EMatologiche dell'Adulto

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

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
172

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Italy
      • Bari, Italy
        • Recruiting
        • Aou Consorziale Policlinico - Bari - Uo Ematologia Con Trapianto
        • Contact:
      • Bari, Italy
        • Recruiting
        • Irccs Oncologico Istituto Tumori Giovanni Paolo Ii - Bari - Uo Ematologia
      • Bologna, Italy
        • Recruiting
        • AOU di Bologna - Policlinico S. Orsola-Malpighi - UOC Ematologia
        • Contact:
      • Brescia, Italy
      • Firenze, Italy
        • Recruiting
        • Aou Careggi- Sod Ematologia
        • Contact:
          • Vannucchi
        • Principal Investigator:
          • Alessandro Vannucchi
      • Latina, Italy
        • Recruiting
        • Asl Latina, Presidio Ospedaliero Nord - Ospedale Santa Maria Goretti - Uoc Ematologia
        • Contact:
      • Lecce, Italy
        • Recruiting
        • Asl Lecce, Ospedale 'V. Fazzi' - Uo Ematologia
      • Mestre, Italy
        • Recruiting
        • Aulss 3 Serenissima, Ospedale Dell'Angelo - Mestre - Uo Ematologia
      • Orbassano, Italy
        • Recruiting
        • Aou San Luigi Gonzaga - Orbassano - Scdu Ematologia Generale E Oncoematologia
        • Contact:
      • Palermo, Italy
        • Recruiting
        • Aou Policlinico P. Giaccone - Palermo - Uo Ematologia
        • Contact:
      • Palermo, Italy
        • Recruiting
        • Ao Ospedali Riuniti Villa Sofia Cervello - Palermo - Uo Ematologia Con Utmo
        • Contact:
      • Pavia, Italy
        • Recruiting
        • Fondazione Ircss Policlinico San Matteo - Pavia - Uo Ematologia
        • Contact:
      • Ravenna, Italy
        • Recruiting
        • Ausl Della Romagna, Ospedale "Santa Maria Delle Croci" - Ravenna - Ematologia
      • Reggio Calabria, Italy
        • Recruiting
        • Grande Ospedale Metropolitano "Bianchi-Melacrino-Morelli" Po E. Morelli - Reggio Calabria - Uoc Ematologia
        • Contact:
      • Reggio Emilia, Italy
        • Recruiting
        • Ausl Di Reggio Emilia - Arcispedale Santa Maria Nuova, Irccs - Sc Ematologia
        • Contact:
      • Rionero In Vulture, Italy
      • Roma, Italy
        • Recruiting
        • Aou Policlinico Tor Vergata - Roma - Uoc Trapianto Cellule Staminali
      • Siena, Italy
        • Recruiting
        • Aou Senese - Uoc Ematologia E Trapianti
        • Contact:
      • Torino, Italy
        • Recruiting
        • Aou Città Della Salute E Della Scienza, Ospedale S. Giovanni Battista Molinette - Torino - Sc Ematologia 2
        • Contact:
      • Torino, Italy

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

14 years to 61 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Active Comparator: Standard clinical treatment
Patients will complete "3+7" + Midostaurin induction course.
Drug: Cytarabine
100 mg/m2/bid day 1-3 100 mg/m2/die day 4-7
Drug: Daunorubicin
60 mg/m2/die day 1-3
Drug: Midostaurin
50 mg/bid day 8-21
Experimental: Experimental treatment

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

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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
2,5 years

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Adverse events rate
Time Frame: 2,5 years
Adverse events rate according to CTCAE criteria
2,5 years
Rate of death in aplasia
Time Frame: 2 months
rate of death in aplasia
2 months
Neutrophil recovery
Time Frame: 2 months
Median number of days for neutrophil recovery
2 months
platelet recovery
Time Frame: 2 months
Median number of days for platelet recovery
2 months
CR rate
Time Frame: 6 months
Complete remission rate after induction
6 months
DFS
Time Frame: 2 years
Disease-free survival
2 years
OS
Time Frame: 2 years
Overall survival
2 years
CIR
Time Frame: 2 years
Cumulative incidence of relapse
2 years
MRD assessment
Time Frame: 6 months
MRD negativity rate at the end of induction and consolidation
6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Gruppo Italiano Malattie EMatologiche dell'Adulto

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
April 24, 2020

Primary Completion (Anticipated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 1, 2022

Study Completion (Anticipated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
August 1, 2025

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
November 11, 2019

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 20, 2019

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
November 22, 2019

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 2, 2022

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 1, 2022

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2022

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • AML1919

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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