NCT05196789

Diagnosis and Phenotype Characterisation Using Genomics in Patients With Inherited Bone Marrow Failure (IBMDx Study)

Diagnosis, Discovery and Novel Phenotype Characterisation Using Multimodal Genomics in Patients With Inherited Bone Marrow Failure and Related Disorders (IBMDx Study)

• Status: Recruiting
• Phase: —
• Study type: Observational
• Enrollment: 350 (estimated)
• Sponsor: Peter MacCallum Cancer Centre, Australia · Academic / Other
• Sex: All
• Age: 3 Months
• Healthy volunteers: Not accepted

Summary

This project seeks to perform whole genome sequence (WGS) and whole transcriptome sequence (WTS) analysis on 350 patients with suspected inherited bone marrow failure syndromes and related disorder (IBMFS-RD) in order to increase the genomic diagnostic rate in IBMFS.

Detailed description

IBMFS-RD are a heterogeneous group of rare diseases resulting in significant morbidity and early mortality. These syndromes are individually and collectively rare (affecting \<1 per 10,000 people) and a significant proportion are unexplained by mutations in known genes. Whilst rare, these familial conditions are also likely underdiagnosed due to their relatively recent description and also due to lack of accessible genomic testing. For patients with clinically suspected IBMFS-RD, receiving a genomic diagnosis is critical to: * Establish a precise and reliable diagnosis (including distinguishing a monogenic aetiology from more common acquired or autoimmune causes of bone marrow failure which have dramatically different treatments (e.g. immunosuppression) * Inform prognosis, clinical course, optimal treatment choice and screening for non-haematological organ dysfunction * Optimise allogeneic haematopoietic stem cell transplant (HSCT) chemotherapy conditioning and minimise regimen-related toxicity * Inform risk-benefit analysis of performing allogeneic HSCT to potentially prioritise other therapies (including novel gene therapy strategies) * Avoiding the catastrophe of HSCT donation from occult genetically affected relatives * Provide counselling (including stem cell donor counselling) and offer genetic testing for potentially affected family members * Provide accurate reproductive counselling and reproductive options to affected individuals This study aims to provide WGS and WTS to a national cohort of patients with IBMFS-RD to determine diagnostic rate, health economic impact, health implementation challenges and other exploratory endpoints.

Conditions

• Inherited BMF Syndrome
• Inherited Platelet Disorder
• Hematologic Diseases

Interventions

Type	Name	Description
DIAGNOSTIC_TEST	whole genome and transcriptome sequencing	To perform whole genome/transcriptome analysis of patients in a cohort of up to 350 Australian patients with IBMFS-RD

Timeline

• Start date: 2022-03-18
• Primary completion: 2025-06-01
• Completion: 2025-12-01
• First posted: 2022-01-19
• Last updated: 2024-11-07

Locations

1 site across 1 country: Australia