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

NCT04641910 | Completed

• 1 other identifier: RC20_0406
• Study Type: observational
• Target: 201
• Locations: 1 country
• Sites: 25

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.

Conditions

Acute Myeloid Leukemia

Outcome Measures

Primary Outcomes (3)

• 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

• 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

• 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 Outcomes (4)

• Confirm that the new FL/IL6 risk-model predicts leukemia free survival in first-line AML patients.

  2 years

• Compare the prognostic impact of the new FL/IL6 risk-model with the impact of other parameters known to predict outcome in AML

  2 years

• Study the impact of the new FL/IL6 risk-model in FLT3 ITD or TKD patients receiving or not FLT3 inhibitors

  2 years

• Study Immune reconstitution during induction

  2 years

Interventions

No intervention OTHER

No intervention

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• 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

You may not qualify if:

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

Sponsors & Collaborators

• Nantes University Hospital: lead

Study Sites (25)

Strasbourg University Hospital

Strasbourg, Bas-Rhin, 67200, France

Location

Paoli-Calmette Institute

Marseille, Bouches-du-Rhône, 13000, France

Location

Besançon University Hospital

Besançon, Doubs, 25000, France

Location

Brest University Hospital

Brest, Finistère, 29200, France

Location

Nîmes University Hospital

Nîmes, Gard, 30000, France

Location

Bordeaux University Hospital

Bordeaux, Gironde, 33076, France

Location

Mulhouse Hospital Center

Mulhouse, Haut-Rhin, 68100, France

Location

Toulouse University Cancer Institute

Toulouse, Haute-Garonne, 31000, France

Location

Béziers Hospital Center

Béziers, Hérault, 34500, France

Location

Montpellier University Hospital

Montpellier, Hérault, 34295, France

Location

Rennes University Hospital

Rennes, Ille-et-Vilaine, 35033, France

Location

Tours University Hospital

Tours, Indre-et-Loire, 37000, France

Location

Grenoble University Hospital

Grenoble, Isère, 38000, France

Location

Nantes University Hospital

Nantes, Loire-Atlantique, 44093, France

Location

Angers University Hospital

Angers, Maine-et-Loire, 49000, France

Location

Reims University Hospital

Reims, Marne, 51100, France

Location

Nancy University Hospital

Nancy, Meurthe-et-Moselle, 54000, France

Location

Mercy Regional Hospital

Metz, Moselle, 57000, France

Location

Saint-Etienne University Hospital

Saint-Étienne-de-Montluc, Pays de la Loire Region, 42000, France

Location

Clermont-Ferrand University Hospital

Clermont-Ferrand, Puy-de-Dôme, 63000, France

Location

Basque coast hospital center

Bayonne, Pyrénées-Atlantiques, 64102, France

Location

Saint-Jean Hospital Center

Perpignan, Pyrénées-Orientales, 66000, France

Location

Lyon University Hospital

Lyon, Rhône, 69000, France

Location

AP-HP Cochin Hospital

Paris, 75014, France

Location

Poitiers University Hospital

Poitiers, 86000, France

Location

Biospecimen

Retention: SAMPLES WITH DNA

Blood samples at day 1, day 8, day 15, day 22, day 30

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 18, 2020
• First Posted: November 24, 2020
• Study Start: June 8, 2021
• Primary Completion: August 31, 2024
• Study Completion: August 31, 2024
• Last Updated: April 16, 2026

Record last verified: 2021-06

Locations

FR (25)