Clinical trial NCT04641910: 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
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
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Acute Myeloid Leukemia
Lead sponsor: Nantes University Hospital
Sponsor class: OTHER
First posted: 2020-11-24
Enrollment: 201
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Any newly diagnosed AML patients treated intensively in centres belonging to the FILO group will be eligible for the FLAMVAL study.

Brief 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.


Eligibility criteria: 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.

Primary outcomes:
measure: 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.
timeFrame: 2 years
measure: 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.
timeFrame: 2 years
measure: 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.
timeFrame: 2 years
Secondary outcomes:
measure: Confirm that the new FL/IL6 risk-model predicts leukemia free survival in first-line AML patients.
timeFrame: 2 years
measure: Compare the prognostic impact of the new FL/IL6 risk-model with the impact of other parameters known to predict outcome in AML
timeFrame: 2 years
measure: Study the impact of the new FL/IL6 risk-model in FLT3 ITD or TKD patients receiving or not FLT3 inhibitors
timeFrame: 2 years
measure: Study Immune reconstitution during induction
timeFrame: 2 years
Other outcomes:
Locations:
city: Strasbourg
country: France
facility: Strasbourg University Hospital
state: Bas-Rhin
city: Marseille
country: France
facility: Paoli-Calmette Institute
state: Bouches-du-Rhône
city: Besançon
country: France
facility: Besançon University Hospital
state: Doubs
city: Brest
country: France
facility: Brest University Hospital
state: Finistère
city: Nîmes
country: France
facility: Nîmes University Hospital
state: Gard
city: Bordeaux
country: France
facility: Bordeaux University Hospital
state: Gironde
city: Mulhouse
country: France
facility: Mulhouse Hospital Center
state: Haut-Rhin
city: Toulouse
country: France
facility: Toulouse University Cancer Institute
state: Haute-Garonne
city: Béziers
country: France
facility: Béziers Hospital Center
state: Hérault
city: Montpellier
country: France
facility: Montpellier University Hospital
state: Hérault
city: Rennes
country: France
facility: Rennes University Hospital
state: Ille-et-Vilaine
city: Tours
country: France
facility: Tours University Hospital
state: Indre-et-Loire
city: Grenoble
country: France
facility: Grenoble University Hospital
state: Isère
city: Nantes
country: France
facility: Nantes University Hospital
state: Loire-Atlantique
city: Saint-Étienne
country: France
facility: Saint-Etienne University Hospital
state: Loire
city: Angers
country: France
facility: Angers University Hospital
state: Maine-et-Loire
city: Reims
country: France
facility: Reims University Hospital
state: Marne
city: Nancy
country: France
facility: Nancy University Hospital
state: Meurthe-et-Moselle
city: Metz
country: France
facility: Mercy Regional Hospital
state: Moselle
city: Clermont-Ferrand
country: France
facility: Clermont-Ferrand University Hospital
state: Puy-de-Dôme
city: Bayonne
country: France
facility: Basque coast hospital center
state: Pyrénées-Atlantiques
city: Perpignan
country: France
facility: Saint-Jean Hospital Center
state: Pyrénées-Orientales
city: Lyon
country: France
facility: Lyon University Hospital
state: Rhône
city: Paris
country: France
facility: AP-HP Cochin Hospital
city: Poitiers
country: France
facility: Poitiers University Hospital
Study officials:
References: