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

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Anticipated)

172

Phase

  • 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

Ages Eligible for Study

16 years to 63 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
Intervention / Treatment
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

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

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

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)

April 24, 2020

Primary Completion (Anticipated)

December 1, 2022

Study Completion (Anticipated)

August 1, 2025

Study Registration Dates

First Submitted

November 11, 2019

First Submitted That Met QC Criteria

November 20, 2019

First Posted (Actual)

November 22, 2019

Study Record Updates

Last Update Posted (Actual)

March 2, 2022

Last Update Submitted That Met QC Criteria

March 1, 2022

Last Verified

March 1, 2022

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID 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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