A Study Investigating the Change in Metabolism Phenotype in Paediatric, Adolescent & Young Adults With Hodgkin or Non-Hodgkin Lymphoma.

Summary

PEGASUS aims to test acceptability and feasibility of studying phenoconversion (the change in metabolism phenotype) using probe medications in a paediatric oncology patient population. The study will be conducted in patients (6-25 years of age) with Hodgkin lymphoma or non-Hodgkin lymphoma as exemplar cohort, but with the understanding that cancer-directed and supportive care medicines of the CYP3A4, CYP2C19, and CYP2D6 metabolic pathways are commonly utilised for the treatment of many paediatric, adolescent, young adult, and adult cancers. The study involves administration of the probe medication at timepoints which align with pre-determined hospital visits for the treatment of lymphoma and subsequent blood draws to measure the metabolism of the probe medications. The acceptability and feasibility of this study will inform future studies in phenoconversion within the paediatric cancer population to direct more personalised precision medicine.

Timeline

Start

2025-07-22

Primary completion

2026-07

Completion

2026-07

Publications

• Background Helsby N, Yong M, Burns K, Findlay M, Porter D. Cyclophosphamide bioactivation pharmacogenetics in breast cancer patients. Cancer Chemother Pharmacol. 2021 Sep;88(3):533-542. doi: 10.1007/s00280-021-04307-0. Epub 2021 Jun 10.
• Background Burns KE, Goldthorpe MA, Porteus F, Browett P, Helsby NA. CYP2C19 genotype-phenotype discordance in patients with multiple myeloma leads to an acquired loss of drug-metabolising activity. Cancer Chemother Pharmacol. 2014 Mar;73(3):651-5. doi: 10.1007/s00280-014-2409-9. Epub 2014 Feb 12.
• Background Kim S, Ostor AJ, Nisar MK. Interleukin-6 and cytochrome-P450, reason for concern? Rheumatol Int. 2012 Sep;32(9):2601-4. doi: 10.1007/s00296-012-2423-3. Epub 2012 Mar 27.
• Background Rodieux F, Daali Y, Rollason V, Samer CF, Ing Lorenzini K. Practice of CYP450 genotyping and phenotyping in children in a real-life setting. Front Pharmacol. 2023 Feb 27;14:1130100. doi: 10.3389/fphar.2023.1130100. eCollection 2023.
• Background Bosilkovska M, Samer CF, Deglon J, Rebsamen M, Staub C, Dayer P, Walder B, Desmeules JA, Daali Y. Geneva cocktail for cytochrome p450 and P-glycoprotein activity assessment using dried blood spots. Clin Pharmacol Ther. 2014 Sep;96(3):349-59. doi: 10.1038/clpt.2014.83. Epub 2014 Apr 10.
• Background Lloret-Linares C, Rollason V, Lorenzini KI, Samer C, Daali Y, Gex-Fabry M, Aubry JM, Desmeules J, Besson M. Screening for genotypic and phenotypic variations in CYP450 activity in patients with therapeutic problems in a psychiatric setting, a retrospective study. Pharmacol Res. 2017 Apr;118:104-110. doi: 10.1016/j.phrs.2016.07.002. Epub 2016 Jul 1.
• Background Rollason V, Lloret-Linares C, Lorenzini KI, Daali Y, Gex-Fabry M, Piguet V, Besson M, Samer C, Desmeules J. Evaluation of Phenotypic and Genotypic Variations of Drug Metabolising Enzymes and Transporters in Chronic Pain Patients Facing Adverse Drug Reactions or Non-Response to Analgesics: A Retrospective Study. J Pers Med. 2020 Oct 27;10(4):198. doi: 10.3390/jpm10040198.
• Background Ing Lorenzini K, Desmeules J, Rollason V, Bertin S, Besson M, Daali Y, Samer CF. CYP450 Genotype-Phenotype Concordance Using the Geneva Micrococktail in a Clinical Setting. Front Pharmacol. 2021 Aug 26;12:730637. doi: 10.3389/fphar.2021.730637. eCollection 2021.
• Background Lenoir C, Niederer A, Rollason V, Desmeules JA, Daali Y, Samer CF. Prediction of cytochromes P450 3A and 2C19 modulation by both inflammation and drug interactions using physiologically based pharmacokinetics. CPT Pharmacometrics Syst Pharmacol. 2022 Jan;11(1):30-43. doi: 10.1002/psp4.12730. Epub 2021 Nov 17.
• Background Mandrioli R, Mercolini L, Protti M. Blood and Plasma Volumetric Absorptive Microsampling (VAMS) Coupled to LC-MS/MS for the Forensic Assessment of Cocaine Consumption. Molecules. 2020 Feb 26;25(5):1046. doi: 10.3390/molecules25051046.
• Background Doerflinger M, Haeusler GM, Li-Wai-Suen CSN, Clark JE, Slavin M, Babl FE, Allaway Z, Mechinaud F, Smyth GK, De Abreu Lourenco R, Phillips B, Pellegrini M, Thursky KA. Procalcitonin and Interleukin-10 May Assist in Early Prediction of Bacteraemia in Children With Cancer and Febrile Neutropenia. Front Immunol. 2021 May 20;12:641879. doi: 10.3389/fimmu.2021.641879. eCollection 2021.
• Conyers R, Stenta T, Somogyi AA, Kirkpatrick C, Halman A, Wang S, Moore C, Khatri D, Williams E, Dyas R, Spelman T, Elliott DA, Gwee A, Alexander M. Phenoconversion of CYP3A4, CYP2C19 and CYP2D6 in Pediatrics, Adolescents and Young Adults With Lymphoma: Rationale and Design of the PEGASUS Study. Clin Transl Sci. 2025 Apr;18(4):e70209. doi: 10.1111/cts.70209.

Drugs

Indications