NCT06886425: CDA-AML-MDS

Involvement of CDA and/or dCK Metabolizing Enzymes in the Response to Azacytidine Treatment of Patients With Hematologic Malignancies

Recruiting now NA Last updated 20 March 2025

What this trial tests

NA trial testing genetic study in Myelodysplastic Syndromes (MDS) in 70 participants. Currently enrolling.

Timeline

14 June 2021

Primary endpoint
14 June 2026

14 June 2028

Quick facts

Lead sponsor	Assistance Publique Hopitaux De Marseille
Phase	NA
Status	Recruiting now
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	other
Enrollment	70
Start date	14 June 2021
Primary completion	14 June 2026
Estimated completion	14 June 2028
Sites	1 location across France

Drugs / interventions tested

• genetic study
• Pharmacokinetic study
• Study of phenotypic activity of cytidine deaminase

Conditions studied

• Myelodysplastic Syndromes (MDS) — all drugs for Myelodysplastic Syndromes (MDS) →
• Leukemia Acute Myeloid - AML — all drugs for Leukemia Acute Myeloid - AML →

Sponsor

Assistance Publique Hopitaux De Marseille — full company profile →

Who can join

18 and older, any sex, with Myelodysplastic Syndromes (MDS) or Leukemia Acute Myeloid - AML. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

Until now, the development of personalized medicine in oncology has relied on the use of somatic biomarkers to help therapists choose the right molecule(s) to administer, based on the genetic and molecular profile of each hematological disease. In this project, investigators propose to extend the strategy of therapeutic individualization to the field of dosage targeting. Today, azacytidine is a standard treatment for patients with acute myeloid leukemia (AML) and/or myelodysplastic syndromes (MDS), usually as monotherapy. According to the treatment regimen, azacytidine is prescribed at a standard dose (DS=75mg/m²/d), administered subcutaneously every day for 7 days. The treatment cycle is repeated every 28 days.

No study has evaluated the relevance of "a priori" dose adjustment on an individual basis, according to each patient's pharmacogenetic data. In current practice, doses are adapted a posteriori, and reduced empirically, following the occurrence of observed toxicity (6 to 71% of patients) (Schuck A et al. 2017). This ex-post adjustment in the face of grade 3-4 toxicity is a loss of chance for the patient. Similarly, under-dosing patients for fear of toxicity is another loss of chance. Investigator's hypothesis is that the optimal dose of azacytidine depends not only on the characteristics of the patient's pathology (risk groups including cytogenetic and molecular biology data), but also on the patient's individual characteristics (genetic status of metabolic enzymes and transporters). A mathematical model of the PK/PD type could, on the basis of early observations of circulating levels, be capable of rapidly predicting the pharmacodynamic repercussions in each patient, thus enabling rapid individualization of dosages. In the future, such a tool could make it possible to propose dosage adjustments rapidly after treatment initiation, before toxicity occurs, by predicting azacytidine exposure levels, themselves correlated with the patient's clinical condition.

Study design: In this open-label, paucicentric, non-randomized study, patients with AML and/or MDS, all of whom are receiving azacytidine-based chemotherapy as part of their standard treatment regimen, will be included. Each patient will be monitored for toxicities (EORTC), treatment response and progression-free survival. In addition to the standard care described above, each patient will undergo a series of constitutional genetic investigations conducted by NGS on markers linked to azacytidine pharmacokinetics (CDA, dCK). Another series of blood samples will be taken to calculate individual azacytidine pharmacokinetic parameters using a Bayesian approach.

Expected results: This study should make it possible to correlate pharmacogenetics with patient plasma exposure, and ultimately improve the molecule's efficacy/toxicity balance by personalizing dosage regimens, which until now have been carried out on an empirical basis.

Prospects: If the data are validated, a pre-therapeutic ADC assay could predict azacytidine pharmacodynamics and enable individual dose and/or dosage adjustment, as is the case with 5-FU and DPD.

Publications & conference data

No peer-reviewed publications indexed yet for this trial.