AMELIORATE: AML Patients Bearing FLT3 Mutations Based on Peripheral Blast Clearance

• Sponsor: Gruppo Italiano Malattie EMatologiche dell'Adulto (Other)
• Overall Status: Recruiting
• CT.gov ID: NCT04174612
• Collaborator: (none)
• Enrollment: 172
• Locations: 20
• Arms: 2
• Anticipated Duration (Months): 63.2
• Patients Per Site: 8.6
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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

Condition or Disease	Intervention/Treatment	Phase
Acute Myeloid Leukemia With FLT3/ITD Mutation	Drug: Cytarabine; Drug: Daunorubicin; Drug: Midostaurin; Drug: Cytarabine HD	Phase 3

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 172 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: Apr 24, 2020
• Anticipated Primary Completion Date: Dec 1, 2022
• Anticipated Study Completion Date: Aug 1, 2025

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Event Free Survival [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

Secondary Outcome Measures

1. Adverse events rate [2,5 years]

   Adverse events rate according to CTCAE criteria

2. Rate of death in aplasia [2 months]

   rate of death in aplasia

3. Neutrophil recovery [2 months]

   Median number of days for neutrophil recovery

4. platelet recovery [2 months]

   Median number of days for platelet recovery

5. CR rate [6 months]

   Complete remission rate after induction

6. DFS [2 years]

   Disease-free survival

7. OS [2 years]

   Overall survival

8. CIR [2 years]

   Cumulative incidence of relapse

9. MRD assessment [6 months]

   MRD negativity rate at the end of induction and consolidation

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Aou Consorziale Policlinico - Bari - Uo Ematologia Con Trapianto	Bari		Italy
2	Irccs Oncologico Istituto Tumori Giovanni Paolo Ii - Bari - Uo Ematologia	Bari		Italy
3	Aou Di Bologna - Policlinico S. Orsola-Malpighi - Uoc Ematologia	Bologna		Italy
4	Asst Degli Spedali Civili Di Brescia - Uo Ematologia	Brescia		Italy
5	Aou Careggi- Sod Ematologia	Firenze		Italy
6	Asl Latina, Presidio Ospedaliero Nord - Ospedale Santa Maria Goretti - Uoc Ematologia	Latina		Italy
7	Asl Lecce, Ospedale 'V. Fazzi' - Uo Ematologia	Lecce		Italy
8	Aulss 3 Serenissima, Ospedale Dell'Angelo - Mestre - Uo Ematologia	Mestre		Italy
9	Aou San Luigi Gonzaga - Orbassano - Scdu Ematologia Generale E Oncoematologia	Orbassano		Italy
10	Ao Ospedali Riuniti Villa Sofia Cervello - Palermo - Uo Ematologia Con Utmo	Palermo		Italy
11	Aou Policlinico P. Giaccone - Palermo - Uo Ematologia	Palermo		Italy
12	Fondazione Ircss Policlinico San Matteo - Pavia - Uo Ematologia	Pavia		Italy
13	Ausl Della Romagna, Ospedale "Santa Maria Delle Croci" - Ravenna - Ematologia	Ravenna		Italy
14	Grande Ospedale Metropolitano "Bianchi-Melacrino-Morelli" Po E. Morelli - Reggio Calabria - Uoc Ematologia	Reggio Calabria		Italy
15	Ausl Di Reggio Emilia - Arcispedale Santa Maria Nuova, Irccs - Sc Ematologia	Reggio Emilia		Italy
16	C.R.O.B. - I.R.C.C.S. - Rionero in Volture - Uoc Ematologia	Rionero In Vulture		Italy
17	Aou Policlinico Tor Vergata - Roma - Uoc Trapianto Cellule Staminali	Roma		Italy
18	Aou Senese - Uoc Ematologia E Trapianti	Siena		Italy
19	Aou Città Della Salute E Della Scienza, Ospedale S. Giovanni Battista Molinette - Torino - Sc Ematologia 2	Torino		Italy
20	Ospedale Mauriziano Umberto I - Torino - Scdu Ematologia	Torino		Italy

Sponsors and Collaborators

• Gruppo Italiano Malattie EMatologiche dell'Adulto

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Gruppo Italiano Malattie EMatologiche dell'Adulto
• ClinicalTrials.gov Identifier: NCT04174612
• Other Study ID Numbers: AML1919
• First Posted: Nov 22, 2019
• Last Update Posted: Mar 2, 2022
• Last Verified: Mar 1, 2022

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Cytarabine; Daunorubicin; Midostaurin

Study Results

No Results Posted as of Mar 2, 2022