Evidence map›Paper›PMID 41432755›Full record

Trial reportEuropean journal of clinical pharmacology2025

Pharmacogenomic, pharmacokinetic, and safety analysis of CYP3A4/CYP3A5 polymorphisms of midostaurin in patients with acute myeloid leukemia.

Romain Sechaud, Thomas Peters, Helen Gu, Gholamreza Rahmanzadeh, Gopal Krishna Sharma, Nathalie Guichard, Hans D Menssen

Registry-linked trialAbstract readClinical Trial, Phase IIIMulticenter StudyRandomized Controlled Trial
PubMed Publisher
In one paragraph

Trial report in European journal of clinical pharmacology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03512197 (A Phase III, Randomized, Double-blind Study of Chemotherapy With Daunorubicin or Idarubicin and Cytarabine for Induction and Intermediate Dose Cytarabine for Consolidation Plus Midostaurin), which is not on this map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT03512197 phase3completednot on this map

A Phase III, Randomized, Double-blind Study of Chemotherapy With Daunorubicin or Idarubicin and Cytarabine for Induction and Intermediate Dose Cytarabine for Consolidation Plus Midostaurin (PKC412) or Chemotherapy Plus Placebo in Newly Diagnosed Patients With FLT-3 Mutation Negative Acute Myeloid Leukemia (AML)

TypeinterventionalSponsorNovartis PharmaceuticalsRan2018 to 2021Enrolled511ConditionsAcute Myeloid Leukemia (AML)ArmsMidostaurin, Placebo, Chemotherapy
3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors.

Romain SechaudNovartis Pharma AG, Basel, CH-4002, Switzerland. romain.sechaud@novartis.com.
Thomas PetersNovartis Pharma AG, Basel, CH-4002, Switzerland.
Helen GuNovartis Pharmaceuticals Corporation, East Hanover, NJ, USA.
Gholamreza RahmanzadehNovartis Pharma AG, Basel, CH-4002, Switzerland.
Gopal Krishna SharmaNovartis Healthcare Pvt. Ltd, Hyderabad, Telangana, 500081, India.
Nathalie GuichardNovartis Pharma AG, Basel, CH-4002, Switzerland.
Hans D MenssenNovartis Pharma AG, Basel, CH-4002, Switzerland.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

purposeMidostaurin is predominantly metabolized by cytochrome P450 (CYP) 3A4 to form two active metabolites, CGP62221 and CGP52421. The current analysis from UNIFY, a randomized, double-blind, phase 3 study, investigated the impact of genetic polymorphism of CYP3A4/CYP3A5 on the exposure of midostaurin and its active metabolites, and on treatment-related toxicity in patients with FLT3-mutation-negative acute myeloid leukemia (AML).

methodsBased on the literature, CYP3A4/CYP3A5 polymorphic variants were selected and further interpreted as individual, combined, and clustered phenotypes. The pharmacokinetic (PK) parameters for midostaurin and the active metabolites were estimated based on concentration data collected after the first dose (full PK profile) and during the induction, consolidation, and post-consolidation phases at trough (pre-dose) and post-dose 3 h. Adverse event (AE) summaries included all treatment-emergent AEs starting on or after study day 1 and starting no later than 30 days after study treatment discontinuation.

resultsPK profiles and parameters of midostaurin and its metabolites after the first dose and multiple dosing, at steady state, at the different visits through different phases of the study were generally comparable across CYP3A4/CYP3A5 polymorphic variants and clustered phenotypes. The safety profile of midostaurin in this study was consistent with the known safety profile of midostaurin in FLT3-mutation-positive patients with AML. No meaningful differences were observed in the safety profile of midostaurin versus placebo in patients with CYP3A4/CYP3A5 polymorphic variants and clustered phenotype groups.

conclusionOur extensive pharmacogenomic/PK/safety analysis in patients with AML does not indicate the need for dose adjustments of midostaurin based on CYP3A4/CYP3A5 polymorphic variants. CLINICALTRIALS.GOV NUMBER: NCT03512197.

Indexed as

Antineoplastic AgentsCytochrome P-450 CYP3ALeukemia, Myeloid, AcuteStaurosporineAdultAgedDouble-Blind MethodFemalefms-Like Tyrosine Kinase 3HumansMaleMiddle AgedPolymorphism, GeneticPolymorphism, Single NucleotideYoung AdultAntineoplastic AgentsCYP3A4 protein, humanCYP3A5 protein, humanCytochrome P-450 CYP3Afms-Like Tyrosine Kinase 3midostaurinStaurosporineCYP3A4CYP3A5MidostaurinPharmacokineticPolymorphismSafety

Identifiers

PMID41432755

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Registered trials

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