Ignite Creation Date:
2024-05-06 @ 10:44 AM
Last Modification Date:
2024-10-26 @ 12:34 PM
Study NCT ID:
NCT03337516
Status:
UNKNOWN
Last Update Posted:
2017-11-09
First Post:
2017-11-06
Brief Title:
Interest of a Therapeutic Follow-up of the Cytarabine in the Acute Myeloid Leukaemia Is There Constitutional Biomarkers
Sponsor:
Assistance Publique Hopitaux De Marseille
Organization:
Assistance Publique Hopitaux De Marseille
Study Overview
Official Title:
Interest of a Therapeutic Follow-up of the Cytarabine in the Acute Myeloid Leukaemia Is There Constitutional Biomarkers
Status:
UNKNOWN
Status Verified Date:
2017-11
Last Known Status:
RECRUITING
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
In this open-label single-center non-randomized patients with AML Acute Myeloid Leukemia and receiving all induction chemotherapy and consolidation consisting of cytarabine under the care usual for this pathology will be included Each patient will be followed and for the development of toxicities treatment response and progression-free survival In addition to the usual care set out above each patient will undergo a series of constitutional genetic investigations conducted by NGS on markers related to pharmacokinetics cytarabine Another set of blood samples will also calculate according to a Bayesian approach individual pharmacokinetics of cytarabine and its metabolite arabinosine-uracil
This study should allow the correlation between pharmacogenetics and patient plasma exposure that would eventually balance improved efficacy toxicity of this molecule through a customization regimens achieved so far on a empirical basis If validation of our data a dosage of therapeutic pre CDA could help in predicting pharmacodynamics of cytarabine individual dose adjustment as is done for the 5-FU and DPD
This study should allow the correlation between pharmacogenetics and patient plasma exposure that would eventually balance improved efficacy toxicity of this molecule through a customization regimens achieved so far on a empirical basis If validation of our data a dosage of therapeutic pre CDA could help in predicting pharmacodynamics of cytarabine individual dose adjustment as is done for the 5-FU and DPD
Detailed Description:
Background and Rationale The development of personalized medicine in oncology has so far relied on the use of somatic biomarkers to inform the therapist about the choice of the molecule or molecules to be administered based on the genetic and molecular profile of each blood disease In this project we propose to extend the therapeutic individualization strategy targeting dosage domain Today cytarabine is one of two pillars of the treatment of leukemia Acute Myeloid Leukemia AML in combination with an anthracycline plus cytarabine 3 7 therapeutic scheme during the induction course and usually during monotherapy consolidation treatments According to the treatment regimens and protocols cytarabine is prescribed at a standard dose SD 100-200mg m² day intermediate dose ID 1 to 15 g 12H for all 3 days or high dose DH 2 to 3 g m² every 12H during 3 days The choice between these different dose levels remains highly debated Lowenberg et al 2013 with a very narrow risk-benefit balance Indeed the various cooperative groups compared two dose regimens with factors between the minimum dose and maximum ranging from 17 times to 34 times between groups Ex Australian arm group 1400 mg m vs 48 000 mg m cumulative dose cytarabine The magnitude of unmatched dose differentials illustrates the complexity of understanding and apprehension of this pivotal molecule for the treatment of AML Despite the many studies that focused on the optimal dose of cytarabine ranging from 1400 mg m² to 90 000 mg m² German group including currently French Intergroup of leukemia-ALFA FILO adult under the BIG1 protocol none evaluated the relevance of the a priori individual dose adjustment depending on the pharmacogenetic patient data In current practice the doses are adapted a posteriori and reduced empirically following the observed toxicity of occurrence 20 of patients Lowenberg et al 2013 This adaptation a posteriori is a loss of opportunity for the patient Similarly under dosed patients for fear of toxicity is also another lost chance Our hypothesis is that the optimal cytarabine dose depends not only on the characteristics of the patients pathology risk groups including cytogenetic data biology molecular but also the patients individual characteristics genetic status of metabolic enzymes and carriers A mathematical model of PK PD kind could based on early observations of circulating levels be able to quickly predict the pharmacodynamic effect in each patient allowing a rapid individualization of dosages Such a tool could enable in future to propose dose adjustments early after initiation of treatment before the onset of toxicity predicting that exposure levels of cytarabine correlate with the patients clinical evolution
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 2017-A00070-53 | OTHER | ANSM | None |