Biological, Prospective Study Evaluating the Dosage of Plasma Cytokines Including the FLT3 Ligand and IL6 of Patients Treated With Non-intensive Chemotherapy (CYTOK-AZA)

Single-center, Biological, Uncontrolled, Prospective Study Evaluating the Dosage of Plasma Cytokines Including the FLT3 (FMS-like Tyrosine Kinase 3) Ligand and IL6 With a View to Making a First Estimate of Their Prognostic Value on the Outcome of Patients Treated With Non-intensive Chemotherapy Such as Azacytidine for Acute Myelogenous Leukemia (AML), High Risk Myelodysplastic Syndrome (HR-MDS) or Chronic Myelomonocytic Leukemia (CMML)

There are 2 possible treatments for the treatment of Acute Myelogenous Leukemia (AML), high-risk myelodysplastic syndromes (HR-MDS) or chronic myelomonocytic leukemia (CMML): intensive curative chemotherapy , and for over-aged or co-morbid patients , non-intensive palliative chemotherapy with a hypomethylating agent (Azacytidine) associated or not with venetoclax.

Pro-inflammatory cytokines and in particular IL-6 (Interleukin 6) seem to play a key role in the chemoresistance of solid cancers and AML : it would be associated with a poor prognosis of AML , would promote the proliferation of leukemic blasts , and would promote the progression of MDS to AML .

In AML treated with intensive chemotherapy, researchers demonstrated that a particular kinetic profile of the FLT3 ligand and IL6 at day 22 could very significantly predict the survival of patients with AML .

It therefore seems interesting to study the plasma cytokine profiles in patients with AML, HR-MDS or CMML treated non-intensively, and to see if researchers observe the same prognostic correlation as during intensive chemotherapy.

Study Overview

• Status: Recruiting
• Conditions: Acute Myeloid Leukemia; Myelodysplastic Syndromes; Chronic Myelomonocytic Leukemia

Detailed Description

Patients will be divided into 2 groups treated according to a non-intensive chemotherapy :

Group 1 : 40 patients treated with Azacytidine and Venetoclax +/- another molecule according to the following schedule:

• Azacytidine 75 mg/m² D1 to D7 SC
• Venetoclax: 400 mg/day orally in 1 dose between 14 and 28 days per cycle. The cycles will be 28 days long and will be carried out until relapse or death. Cytokine assays will be carried out on D1, D8, D15 and D22 of each cycle for 2 cycles.

Group 2 : 20 patients treated with Azacytidine +/- another molecule according to the following schedule:

• Azacytidine 75 mg/m² D1 to D7 SC The cycles will be 28 days long and will be carried out until relapse or death. The cytokine assays will be carried out on D1, D8, D15 and D22 of each cycle for 3 cycles.

The duration of follow-up for a patient is 12 months from day 1 of the first cycle.

• Study Type: Observational
• Enrollment (Estimated): 60

Contacts and Locations

• Study Contact: Name: Alice GARNIER, PH; Phone Number: 33 2 44 76 80 81; Email: alice.garnier@chu-nantes.fr

Study Locations

• France
  • Loire-Atlantique
    • Nantes, Loire-Atlantique, France, 44093
      • Recruiting
      • Nantes university hospital
      • Contact: Alice GARNIER, PH; Phone Number: 33 2 44 76 80 81; Email: alice.garnier@chu-nantes.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: N/A

• Sampling Method: Non-Probability Sample

Study Population

40 patients treated with Azacytidine and Venetoclax +/- another molecule and 20 patients treated with Azacytidine +/- another molecule.

Description

Inclusion Criteria :

• Age >=18 years
• AML or SMD-HR or CMML in first line or in relapse receiving a hypomethylating agent +/- another molecule or a hypomethylating agent in combination with venetoclax +/- another molecule.
• Patient having agreed to participate in the study (information note signature) and having signed the biocollection consent

Exclusion Criteria :

• No social security or any other regime
• Pregnant women or patient unable to take contraception in case of fertility
• Breastfeeding women
• Minors
• Adults under guardianship, curators or safeguard of justice

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Azacytidine and Venetoclax; 40 patients treated with Azacytidine and Venetoclax +/- another molecule according to the following schedule: Azacytidine 75 mg/m² D1 to D7 SC; Venetoclax: 400 mg/day orally in 1 dose between 14 and 28 days per cycle. The cycles will be 28 days long and will be carried out until relapse or death. Cytokine assays will be carried out on D1, D8, D15 and D22 of each cycle for 2 cycles.
Azacytidine; 20 patients treated with Azacytidine +/- another molecule according to the following schedule: • Azacytidine 75 mg/m² D1 to D7 SC The cycles will be 28 days long and will be carried out until relapse or death. The cytokine assays will be carried out on D1, D8, D15 and D22 of each cycle for 3 cycles. The duration of follow-up for a patient is 12 months from day 1 of the first cycle.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluation of cytokine profiles (Flt3-L, IL (Interleukin) 1beta, IL6, IL8/CXCL8, IL10, IL15, IL17A, IL17E, IL17-F, IL18, GM-CSF, TNFalpha) in patients treated non-intensively for AML, SMD-HR or an LMMC.	Determination of plasma cytokines (Flt3-L, IL1beta, IL6, IL8/CXCL8, IL10, IL15, IL17A, IL17E, IL17-F, IL18, GM-CSF (granulocyte-monocyte colony-stimulating factor, TNFalpha) by Luminex at diagnosis and during treatment of adult patients with of AML, SMD-HR (High risk myelodysplastic syndrome) or CMML(Chronic myelomonocytic leukemia) treated non-intensively	2 years

Collaborators and Investigators

• Sponsor: Nantes University Hospital
• Collaborators: Institut National de la Santé Et de la Recherche Médicale, France

Study record dates

Study Major Dates

• Study Start (Actual): September 23, 2024
• Primary Completion (Estimated): July 15, 2028
• Study Completion (Estimated): December 15, 2029

Study Registration Dates

• First Submitted: February 9, 2024
• First Submitted That Met QC Criteria: May 31, 2024
• First Posted (Actual): June 3, 2024

Study Record Updates

• Last Update Posted (Actual): September 9, 2026
• Last Update Submitted That Met QC Criteria: September 8, 2026
• Last Verified: September 1, 2026

More Information

Terms related to this study

• Keywords: AML; Cytokine; CMML; Azacytidine; FLT3 Ligand; IL 6; HR MDS
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Chronic Disease; Disease Attributes; Neoplasms by Histologic Type; Hematologic Diseases; Leukemia, Myeloid; Myelodysplastic-Myeloproliferative Diseases; Bone Marrow Diseases; Leukemia; Pathological Conditions, Signs and Symptoms; Hemic and Lymphatic Diseases; Leukemia, Myeloid, Acute; Leukemia, Myelomonocytic, Chronic; Myelodysplastic Syndromes
• Other Study ID Numbers: RC23_0332

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No