Validation Study of a New Cytokine-based Dynamic Stratification Based on FLt3 Ligand Plasma Concentration Kinetic Profile and IL-6 Concentration During Induction of Acute Myeloid Leukemia

Acute Myeloid Leukemia Clinical Trial

— FLAMVAL  

Official title:

Validation Study of a New Cytokine-based Dynamic Stratification Based on FLt3 Ligand Plasma Concentration Kinetic Profile and IL-6 Concentration During Induction of Acute Myeloid Leukemia

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04641910
• Other study ID #: RC20_0406
• Status: Recruiting
• Start date: June 8, 2021
• Est. completion date: June 8, 2025

Study information

• Verified date: June 2021
• Source: Nantes University Hospital
• Contact: Pierre Peterlin
• Phone: 0240087418
• Email: pierre.peterlin[@]chu-nantes.fr
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The investigators have recently demonstrated the strong impact in terms of survivals of Fms-like tyrosine kinase 3 ligand (FL) levels evaluated during intensive induction in acute myeloid leukemia (AML) patients. Indeed, three FL kinetic profiles were delineated: i) sustained increase of FL concentrations between day (D) 1 and D22 (FLI group, n=26, good-risk), ii) increase from D1 to D15, then decrease at D22 (FLD group, n=22, intermediate-risk) and iii) stagnation of low levels (<1000 pg/mL, FLL group, n=14, high-risk). However, with longer follow-up, the investigators have observed that FLI and FLD shared similar outcomes while FLL sub-group kept a very bad prognostic. Because serum samples from this previous study (called the FLAM/FLAL study) had been frozen-stored, the investigators were able to conduct an ancillary study assessing the potential impact of the kinetics of 6 other cytokines: TNFalpha, stem-cell factor, IL-1beta, IL-6, IL-10 and granulocyte-monocyte colony-stimulating factor (GM-CSF).. Only Il-6 level at D22 (< or >15.5 pg/mL) was associated with outcome allowing to distinguish between higher and lower survivals within the combined FLI/FLD sub-group. A new prognostic risk-stratification can thus be proposed as follows: FLI/FLD with IL-6 <15.5 pg/mL (favorable), FLI/FLD with IL-6 >15.5 pg/mL (intermediate) and FLL (high-risk). The aim of this new FLAMVAL study is to validate prospectively in a larger and independent cohort this prognostic risk-stratification i.e. that kinetic profile of FLT3L plasma level from D1 to D22 and Il6 plasma level at day 22 during induction of AML patients are predictive of overall and disease free survivals. For that purpose, 201 newly diagnosed AML patients treated intensively in the 25 centres of the French Innovative Leukemia Organisation (FILO) will be included in the FLAMVAL study.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 201
• Est. completion date: June 8, 2025
• Est. primary completion date: June 8, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Age >= 18 years old
• Confirmed diagnosis of AML according to World Health Organization (WHO) 2016 classification (Arber et al., 2016)
• Non previously treated AML (first-line therapy)
• Patients eligible to standard 3+7 induction chemotherapy with a minimum of 3 days of daunorubicin at 45mg/m2/day or a minimum of 5 days of idarubicin at 8mg/m2/day and a minimum of 7 days of cytarabin at 100mg/m2/day
• Patients receiving any "third drug" combined to the "3+7" scheme, i.e. lomustine, corticotherapy, elthrombopag, gemtuzumab-ozogamycin, any FLT3 inhibitors… are eligible
• Patients receiving CPX-351 (Vyxeos ®) are eligible
• Patients requiring leukapheresis are eligible
• Signed informed consent

Exclusion Criteria:

• Patients diagnosed with Acute Promyelocytic Leukemia (AML-3)
• Adults under guardianship, subjects under protection.

Related Conditions & MeSH terms

• Acute Myeloid Leukemia
• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute

Intervention

Other:
• No intervention
No intervention

Locations

Country	Name	City	State
France	Angers University Hospital	Angers	Maine-et-Loire
France	Basque coast hospital center	Bayonne	Pyrénées-Atlantiques
France	Besançon University Hospital	Besançon	Doubs
France	Béziers Hospital Center	Béziers	Hérault
France	Bordeaux University Hospital	Bordeaux	Gironde
France	Brest University Hospital	Brest	Finistère
France	Clermont-Ferrand University Hospital	Clermont-Ferrand	Puy-de-Dôme
France	Grenoble University Hospital	Grenoble	Isère
France	Lyon University Hospital	Lyon	Rhône
France	Paoli-Calmette Institute	Marseille	Bouches-du-Rhône
France	Mercy Regional Hospital	Metz	Moselle
France	Montpellier University Hospital	Montpellier	Hérault
France	Mulhouse Hospital Center	Mulhouse	Haut-Rhin
France	Nancy University Hospital	Nancy	Meurthe-et-Moselle
France	Nantes University Hospital	Nantes	Loire-Atlantique
France	Nîmes University Hospital	Nîmes	Gard
France	AP-HP Cochin Hospital	Paris
France	Saint-Jean Hospital Center	Perpignan	Pyrénées-Orientales
France	Poitiers University Hospital	Poitiers
France	Reims University Hospital	Reims	Marne
France	Rennes University Hospital	Rennes	Ille-et-Vilaine
France	Saint-Etienne University Hospital	Saint-Étienne	Loire
France	Strasbourg University Hospital	Strasbourg	Bas-Rhin
France	Toulouse University Cancer Institute	Toulouse	Haute-Garonne
France	Tours University Hospital	Tours	Indre-et-Loire

Sponsors (1)

Lead Sponsor	Collaborator
Nantes University Hospital

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Confirm that the combination of the kinetic profile of FLT3L plasma levels and the IL-6 plasma level at day22 during induction in AML patients is predictive of overall survival.	time from day 1 of induction to the date of death or of last follow-up	2 years
Primary	Confirm that the combination of the kinetic profile of FLT3L plasma levels and the IL-6 plasma level at day22 during induction in AML patients is predictive of overall survival.	serum FL concentration is measured at day 1, 8, 15 et 22 of induction by ELISA	2 years
Primary	Confirm that the combination of the kinetic profile of FLT3L plasma levels and the IL-6 plasma level at day22 during induction in AML patients is predictive of overall survival.	level of IL-6 at day 22 has been also shown to have prognostic impact for FLD/FLI patients	2 years
Secondary	Confirm that the new FL/IL6 risk-model predicts leukemia free survival in first-line AML patients.	Progression-free survival (PFS): time from day 1 of induction to refractory disease or relapse censored at the date of death or last follow-up	2 years
Secondary	Compare the prognostic impact of the new FL/IL6 risk-model with the impact of other parameters known to predict outcome in AML	Refractory status after induction	2 years
Secondary	Study the impact of the new FL/IL6 risk-model in FLT3 ITD or TKD patients receiving or not FLT3 inhibitors	cytokines plasma levels	2 years
Secondary	Study Immune reconstitution during induction	By flow cytometry	2 years