Minimising Adverse Drug Reactions and Verifying Economic Legitimacy in Children (MARVEL-PIC)

NCT05667766 | Recruiting DMC

• 1 other identifier: 89083
• Study Type: interventional
• Target: 880
• Locations: 1 country
• Sites: 4

Brief Summary

A prospective, open, randomised implementation study in paediatric cancer patients. The study aims to determine whether a personalised approach will result in an overall reduction in clinically relevant adverse drug reactions (ADRs) and to evaluate the economic and quality of life impacts. Participants will be randomised to receive personalised guided prescribing of supportive care therapy (study arm) or standard of care (control arm) for a period of 12 weeks. The follow up period includes prospective patient reporting of symptoms and quality of life through electronically delivered surveys, for a maximum of 12 months.

Conditions

Neoplasms; Bone Marrow Transplantation

Keywords

cancer; paediatric; pharmacogenomic

Outcome Measures

Primary Outcomes (1)

• Reduction in the number of adverse drug reactions (ADRs)

  The primary outcome is a reduction in adverse drug reactions among patients with actionable pharmacogenomic variants. An adverse drug reaction will be considered as any CTCAE grade 2 and above for non-haematological toxicities or CTCAE grade 3 and above for haematological toxicities. CTCAE grades are defined as 1,2,3,4 or 5, with 5 indicating the most severe.

  12 weeks

Secondary Outcomes (11)

• Occurrence of at least one ADR which contributes to primary endpoint

  12 weeks

• Occurrence of at least one causal, clinically relevant, drug-genotype specific ADR, attributable to the index drug.

  12 weeks

• Number of self-reported ADRs

  12 weeks

• Number of serious self-reported ADRs

  12 weeks

• Number of dose adjustments

  12 weeks

Study Arms (2)

Standard of Care

OTHER

Standard of Care prescribing for period of 12 months. Participants will receive pharmacogenomic test results according to the current standard of care. The participants will be followed up for a minimum of 12 weeks, with maximal time-period being 12 months depending on time of enrolment.

Diagnostic Test: Release of Extended Pharmacogenomics Report at Week 13

Experimental Arm

EXPERIMENTAL

Extended Pharmacogenomic prescribing for a period of 12 months. Participants will receive pharmacogenomic testing across a range of clinically relevant variants, to guide the dose and drug selection of 27 drugs commonly used in supportive care. The participants will be followed up for a minimum of 12 weeks, with maximal time-period being 12 months depending on time of enrolment.

Diagnostic Test: Release of Extended Pharmacogenomics Report at Week 1; Diagnostic Test: Release of Extended Pharmacogenomics Report at Week 13

Interventions

Release of Extended Pharmacogenomics Report at Week 1 DIAGNOSTIC_TEST

Whole genome sequencing with reporting on current standard of care (SoC) pharmacogenomic variants (TPMT, NUD15) where applicable (i.e, for patients with diagnosis of acute lymphoblastic leukaemia) by Week 1. Whole genome sequencing on a broader number of actionable variants as per international guidelines for cancer supportive care (identical to study arm) will be reported on at Week 13.

Experimental Arm

Release of Extended Pharmacogenomics Report at Week 13 DIAGNOSTIC_TEST

Whole genome sequencing with reporting on current standard of care (SoC) pharmacogenomic variants (TPMT, NUD15) where applicable (i.e, for patients with diagnosis of acute lymphoblastic leukaemia) and reporting of a broader number of actionable pharmacogenomic variants as per international guidelines for cancer supportive care reported on by Week 1.

Experimental Arm; Standard of Care

Eligibility Criteria

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

You may qualify if:

• Age \< 18 years
• New cancer diagnosis or patient receiving HSCT or patient has a relapsed cancer diagnosis and is starting treatment after more than 6 months without.
• Starting treatment with a chemotherapeutic agent that is not single agent oral targeted therapy.
• Must also be taking a medication for which there is an established CPIC guideline available.
• Parent or patient is able and willing to give consent for patient to take part and be followed up for at least 12 weeks.
• Patient is amenable to venepuncture and blood draw (5mL ideally with an absolute minimum requirement of 2.5 mL) or has Whole Genome Sequencing available (WGS).
• Patient and/or parent is able and willing to sign an informed consent form.
• Patient and/or parent is able to complete Ped-PRO-CTCAE survey in English, Italian or Chinese.
• Study enrolment limit has not been reached.

You may not qualify if:

• Age \> 18 years.
• Patient has a life expectancy estimated to be less than three months by the treating clinical team.
• Patient and/or parent is unable to consent to the study.
• Patient and/or parent is unwilling to take part in the study.
• Patient and/or parent is able unable to complete Ped-PRO-CTCAE survey in English, Italian or Chinese.
• Patient has existing impaired hepatic or renal function for which a lower dose or alternate drug selection are already part of current routine care.
• Patient has a glomerular filtration rate of less than 15 mL/min per 1.73m2.
• Patient has advanced liver failure.

Sponsors & Collaborators

• Murdoch Childrens Research Institute: lead

Study Sites (4)

Sydney Children's Hospital

Randwick, New South Wales, 2031, Australia

RECRUITING

Women's and Children's Hospital

North Adelaide, South Australia, 5006, Australia

RECRUITING

The Royal Children's Hospital

Parkville, Victoria, 3052, Australia

RECRUITING

Perth Children's Hospital

Nedlands, Washington, 6009, Australia

RECRUITING

Related Publications (1)

• Conyers R, Halman A, Moore C, Stenta T, Felmingham B, Collier L, Khatri D, Spelman T, Williams E, Dyas R, Kotecha RS, Jessop S, Mateos MK, Swen J, Elliott DA. Minimising Adverse Drug Reactions and Verifying Economic Legitimacy-Pharmacogenomics Implementation in Children (MARVEL- PIC): protocol for a national randomised controlled trial of pharmacogenomics implementation. BMJ Open. 2024 May 16;14(5):e085115. doi: 10.1136/bmjopen-2024-085115.

  PMID: 38760050 DERIVED

MeSH Terms

Conditions

Neoplasms

Study Officials

• A/Prof Rachel Conyers

  The Royal Children's Hospital/Murdoch Children's Research Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Tayla Stenta

CONTACT

03 9345 5533; pharmaco.genomics@mcri.edu.au

Claire Moore

CONTACT

03 9345 5533; pharmaco.genomics@mcri.edu.au

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 19, 2022
• First Posted: December 29, 2022
• Study Start: March 22, 2023
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): August 1, 2027
• Last Updated: July 18, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: The de-identified data set collected for the analysis of the trial will be available from six months after publication of the primary outcome. The study protocol can be obtained from Murdoch Children's Research Institute. Prior to access to any data the following would be required: a data access agreement must be signed by all relevant parties, the investigators of the study must see and approve the analysis plan describing how the data will be analysed. There must be also an agreement around appropriate acknowledgement in any future publications.
• Access Criteria: The data may be obtained from the Melbourne Children's Trials Centre (MCTC) at Murdoch Children's Research Institute by emailing MCTC@mcri.edu.au.

Locations

AU (4)