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

NCT06383338 | Recruiting Phase 1

• 1 other identifier: PEGASUS 2023/ETH01954
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Hodgkin Lymphoma; Non Hodgkin Lymphoma

Keywords

Phenoconversion

Outcome Measures

Primary Outcomes (1)

• Proportion of patients who consent to study and complete baseline and at least two longitudinal timepoints with successful measurement of probe drug MR (Metabolic ratio)

  This measure is to help inform whether future studies of this nature are feasible and identify if any procedures need to be adjusted to ensure study participant completion.

  12 months, 24 Months

Secondary Outcomes (12)

• Percentage of participants completing all required longitudinal blood sampling

  Baseline through to 24 Months

• Proportion of participants with successful detection of probe drug overall and at each sampling timepoint

  Baseline through to 24 Months

• Proportion of participants where phenotype can be classified according to MR overall at each sampling timepoint

  Baseline through to 24 Months

• The level of acceptability of participation in pharmacogenomic & phenoconversion testing using the PEGASUS specific survey tool (based on the Theoretical Framework of Acceptability [TFA])

  Baseline through to 24 Months

• Percentage of participants experiencing an adverse event (AE) during probe drug administration

  Baseline through to 24 Months

Interventions

Omeprazole DRUG

Sub-therapeutic probe drug administration to measure phenoconversion.

Dextromethorphan DRUG

Sub-therapeutic probe drug administration to measure phenoconversion.

Eligibility Criteria

• Age: 6 Years - 25 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Age 6-25 years of age.
• New diagnosis of Hodgkin Lymphoma or Non-Hodgkin Lymphoma.
• Able to swallow and absorb oral or nasogastric tube (NGT) administration of probe drugs.
• Able to provide written informed consent.

You may not qualify if:

• Has a known previous allergy to any of the probe medications (i.e., omeprazole or dextromethorphan).
• Common Terminology Criteria for Adverse Events (CTCAE) Grade IV end organ dysfunction (i.e., hepatic, renal, gastrointestinal).
• Had previous oncological treatment (not first cancer diagnosis).
• Is a clinically unstable patient requiring intensive care admission in high-risk circumstances will not be considered eligible for consent.
• Any patient requiring urgent initiation of anti-cancer treatment outside hours where a member of the study staff is unable to approach the parent/guardian or participant for consent prior to commencing anti-cancer therapy will be ineligible for consent.
• Unable to provide written informed consent.

Sponsors & Collaborators

• Murdoch Childrens Research Institute: lead

Study Sites (1)

Peter MacCallum Cancer Centre

Melbourne, Victoria, 3000, Australia

RECRUITING

Related Publications (12)

• 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.

  PMID: 34114066 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.

  PMID: 24519754 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.

  PMID: 22451032 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.

  PMID: 36937881 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.

  PMID: 24722393 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.

  PMID: 27378571 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.

  PMID: 33121061 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.

  PMID: 34512355 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.

  PMID: 34791831 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.

  PMID: 32110941 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.

  PMID: 34093531 BACKGROUND

• 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.

  PMID: 40259519 DERIVED

MeSH Terms

Conditions

Hodgkin Disease; Lymphoma, Non-Hodgkin

Interventions

Omeprazole; Dextromethorphan

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

2-Pyridinylmethylsulfinylbenzimidazoles; Sulfoxides; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds

Study Officials

• Rachel Conyers, MBBS (Hons)

  Murdoch Childrens Research Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Rachel Conyers, MBBS (Hons)

CONTACT

+61393455522; rachel.conyers@mcri.edu.au

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 21, 2024
• First Posted: April 25, 2024
• Study Start: July 22, 2025
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): July 1, 2026
• Last Updated: September 8, 2025

Record last verified: 2025-09

Locations

AU (1)