Clinical trial NCT06383338: A Study Investigating the Change in Metabolism Phenotype in Paediatric, Adolescent & Young Adults With Hodgkin or Non-Hodgkin Lymphoma.
Official title: A Prospective Feasibility Study Investigating PhEnoconversion of CYP3A4, CYP2C19 and CYP2D6 Genotype in Paediatric and Adolescent and Young Adult patientS With an acUte diagnosiS of Hodgkin or Non-Hodgkin Lymphoma.
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
Conditions: Hodgkin Lymphoma
Non Hodgkin Lymphoma
Keywords: Phenoconversion
Lead sponsor: Murdoch Childrens Research Institute
Sponsor class: OTHER
First posted: 2024-04-25
Enrollment: 10
Sex: ALL
Minimum age (years): 6
Maximum age (years): 25
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

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.


Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* Failure to comply with inclusion criteria.
* 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.

Primary outcomes:
measure: 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)
timeFrame: 12 months, 24 Months
Secondary outcomes:
measure: Percentage of participants completing all required longitudinal blood sampling
timeFrame: Baseline through to 24 Months
measure: Proportion of participants with successful detection of probe drug overall and at each sampling timepoint
timeFrame: Baseline through to 24 Months
measure: Proportion of participants where phenotype can be classified according to MR overall at each sampling timepoint
timeFrame: Baseline through to 24 Months
measure: The level of acceptability of participation in pharmacogenomic & phenoconversion testing using the PEGASUS specific survey tool (based on the Theoretical Framework of Acceptability [TFA])
timeFrame: Baseline through to 24 Months
measure: Percentage of participants experiencing an adverse event (AE) during probe drug administration
timeFrame: Baseline through to 24 Months
measure: Incidence of genotype and phenotype mismatch, overall and across longitudinal timepoints
timeFrame: Baseline through to 24 Months
measure: Proportion of participants with disease staging and biomarkers of extent of disease
timeFrame: Baseline through to 24 Months
measure: Proportion of participants with a systemic inflammatory state
timeFrame: Baseline through to 24 Months
measure: Proportion of participants taking medications involving the CYP P450 pathway
timeFrame: Baseline through to 24 Months
measure: Participant demographic information
timeFrame: Baseline
measure: Proportion of participants with other environmental factors
timeFrame: Baseline through to 24 Months
measure: Longitudinal inflammatory profile of participants with Hodgkin or non-Hodgkin Lymphoma as measured by a panel including serum levels of procalcitonin, c-reactive protein and cytokine analysis.
timeFrame: Baseline through to 24 Months
Other outcomes:
Locations:
city: Melbourne
country: Australia
facility: Peter MacCallum Cancer Centre
state: Victoria
Study officials:
affiliation: Murdoch Childrens Research Institute
name: Rachel Conyers, MBBS (Hons)
role: PRINCIPAL_INVESTIGATOR
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