Diagnosis and Phenotype Characterisation Using Genomics in Patients With Inherited Bone Marrow Failure (IBMDx Study)
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: whole genome and transcriptome sequencing.
- Who it may be relevant to
- Registry conditions: Inherited BMF Syndrome, Inherited Platelet Disorder, Hematologic Diseases. Basic parameters: from 3 months · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- Australia
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
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Official title
Diagnosis, Discovery and Novel Phenotype Characterisation Using Multimodal Genomics in Patients With Inherited Bone Marrow Failure and Related Disorders (IBMDx Study)
Overview
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.
Interventions
- 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
Primary outcome measures
- Definitive IBMFS-RD diagnosis [Time frame: 3-12 months post baseline]
Secondary outcome measures (5)
- Develop a whole transcriptome gene expression classifier [Time frame: 4 years]
- Cost-effectiveness of genomic testing in patients with suspected IBMFS-RD [Time frame: 4 years]
- Budget-impact of genomic testing in patients with suspected IBMFS-RD [Time frame: 4 years]
- Health implementation analyses regarding the acceptability of genomic testing [Time frame: 4 years]
- Populate Registry [Time frame: 4 years]
Eligibility criteria
Inclusion criteria
- age ≥ 3 months
- able to give informed consent (or parent/guardian able to give informed consent)
- a clinicopathological diagnosis (or differential diagnosis) of inherited bone marrow failure syndrome or related disorder (IBMFS-RD) as per the study team
Exclusion criteria
- A clinicopathological diagnosis of an acquired bone marrow failure syndrome (including acquired aplastic anaemia and hypoplastic myelodysplastic syndrome) as per the study team
- Existing definitive genomic diagnosis for patient's haematological phenotype
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Observational model
- Other
Study locations
Australia · 1 center
- Peter MacCallum Cancer Centre — Melbourne
Publications
- Blombery P, Fox L, Ryland GL, Thompson ER, Lickiss J, McBean M, Yerneni S, Trainer A, Hughes D, Greenway A, Mechinaud F, Wood EM, Lieschke GJ, Szer J, Barbaro P, Roy J, Wight J, Lynch E, Martyn M, Gaff C, Ritchie D. Utility of clinical comprehensive genomic characterization for diagnostic categorization in patients presenting with hypocellular bone marrow failure syndromes. Haematologica. 2021 Jan PMID 32054657
Identifiers
NCT: NCT05196789 · 77923