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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 (FLAMVAL)

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ClinicalTrials.gov Identifier: NCT04641910
Recruitment Status : Recruiting
First Posted : November 24, 2020
Last Update Posted : August 26, 2021
Sponsor:
Information provided by (Responsible Party):
Nantes University Hospital

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.


Condition or disease Intervention/treatment
Acute Myeloid Leukemia Other: No intervention

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Study Type : Observational
Estimated Enrollment : 201 participants
Observational Model: Case-Only
Time Perspective: Prospective
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
Actual Study Start Date : June 8, 2021
Estimated Primary Completion Date : June 8, 2023
Estimated Study Completion Date : June 8, 2025



Intervention Details:
  • Other: No intervention
    No intervention


Primary Outcome Measures :
  1. 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 Frame: 2 years ]
    time from day 1 of induction to the date of death or of last follow-up

  2. 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 Frame: 2 years ]
    serum FL concentration is measured at day 1, 8, 15 et 22 of induction by ELISA

  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 Frame: 2 years ]
    level of IL-6 at day 22 has been also shown to have prognostic impact for FLD/FLI patients


Secondary Outcome Measures :
  1. Confirm that the new FL/IL6 risk-model predicts leukemia free survival in first-line AML patients. [ Time Frame: 2 years ]
    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. Compare the prognostic impact of the new FL/IL6 risk-model with the impact of other parameters known to predict outcome in AML [ Time Frame: 2 years ]
    Refractory status after induction

  3. Study the impact of the new FL/IL6 risk-model in FLT3 ITD or TKD patients receiving or not FLT3 inhibitors [ Time Frame: 2 years ]
    cytokines plasma levels

  4. Study Immune reconstitution during induction [ Time Frame: 2 years ]
    By flow cytometry


Biospecimen Retention:   Samples With DNA
Blood samples at day 1, day 8, day 15, day 22, day 30


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04641910


Contacts
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Contact: Pierre Peterlin 0240087418 pierre.peterlin@chu-nantes.fr

Locations
Show Show 25 study locations
Sponsors and Collaborators
Nantes University Hospital
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Responsible Party: Nantes University Hospital
ClinicalTrials.gov Identifier: NCT04641910    
Other Study ID Numbers: RC20_0406
First Posted: November 24, 2020    Key Record Dates
Last Update Posted: August 26, 2021
Last Verified: June 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasms by Histologic Type
Neoplasms