Inherited BMF SyndromeIBMDxNCT05196789
Diagnosis and Phenotype Characterisation Using Genomics in Patients With Inherited Bone Marrow Failure (IBMDx Study)
An observational study of Inherited BMF Syndrome and Inherited Platelet Disorder, run by Peter MacCallum Cancer Centre, Australia at 1 site in Australia.
Trial 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. Read more about this study
- Who is it for?
- Ages 3 months and older
- Conditions the study is for
- Inherited BMF Syndrome, Inherited Platelet Disorder, Hematologic Diseases
- What is being tested?
- whole genome and transcriptome sequencing
- How many people
- 350 participants
- Where
- 1 siteAustralia
- Study dates
- 18 Mar 2022to Dec 2025
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 3 months and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: Patients with suspected IBMFS-RD
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Piers Blombery, MBBS(Hons) contact
Australia1 site, 1 recruiting
- Recruiting
Peter MacCallum Cancer Centre
Melbourne, Victoria
About this study
Official title: Diagnosis, Discovery and Novel Phenotype Characterisation Using Multimodal Genomics in Patients With Inherited Bone Marrow Failure and Related Disorders (IBMDx Study)
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.
Read the 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.
- Being tested
- whole genome and transcriptome sequencing
- Keywords
- bone marrow failure syndrome, whole genome sequencing, hematological diseases, pancytopenia
- Medical subject headings
- Congenital Bone Marrow Failure Syndromes, Hematologic Diseases, Bone Marrow Failure Disorders, Pancytopenia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
whole genome and transcriptome sequencingDiagnostic test
To perform whole genome/transcriptome analysis of patients in a cohort of up to 350 Australian patients with IBMFS-RD
What is being measured
The primary outcome is the main question the study is designed to answer.
Definitive IBMFS-RD diagnosis
IBMFS-RD diagnosis - An initial analysis of a panel of ~100 genes of established relevance to IBMFS-RD phenotype will be performed on all patients. If no molecular diagnosis is made from the panel of genes, further analysis on the genomic data will be performed using the best practice analytical tools and techniques.
All results will be communicated to patients.
Measured: 3-12 months post baseline
Secondary outcomes (5)
Develop a whole transcriptome gene expression classifier
To develop a whole transcriptome gene expression classifier to aid diagnosis of IBMFS-RD.
Measured: 4 years
Cost-effectiveness of genomic testing in patients with suspected IBMFS-RD
The cost-effectiveness of genomic testing is assessed by the differences in costs and quality of life associated with genomic testings compared with standard of care. Costs being considered include direct medical costs incurred within the health system arising from utilisation of hospital services and drug dispensing. Quality of life is assessed by EORTC-QLQ-C30 version 3 and CHU9D questionnaires for adult and paediatric patients respectively.
Measured: 4 years
Budget-impact of genomic testing in patients with suspected IBMFS-RD
Evaluation of budget-impact of genomic testing includes examining the financial and operational sustainability as well as scalability of offering genomic testing beyond the trial period.
Measured: 4 years
Health implementation analyses regarding the acceptability of genomic testing
The acceptability of comprehensive and centralised genomic testing in IBMFS-RD to patients is measured by a patient acceptability questionnaire which assesses patients' view and understanding of genomic testing.
Measured: 4 years
Populate Registry
To populate the Aplastic Anaemia and Other Bone Marrow Failure Syndromes Registry (AAR, Monash University) with consenting patients with IBMFS-RD to facilitate long-term follow up.
Measured: 4 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Jan 2022
- Study start18 Mar 2022
- Primary completionJun 2025 (estimated)
- Study completionDec 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Inherited BMF SyndromeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Other
- Time perspective
- Prospective
- Enrolment
- 350 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Peter MacCallum Cancer Centre, Australia
- Sponsor type
- University, hospital or other
- Collaborators
- National Health and Medical Research Council, Australia, University of Melbourne
- Responsible party
- Sponsor
- Investigators
- Piers Blombery, MBBS(Hons), Principal investigator, Peter MacCallum Cancer Centre, Australia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05196789
- Sponsor's protocol ID
- 77923
- Acronym
- IBMDx
- Status last verified
- Nov 2024
- First submitted
- 15 Dec 2021
- Last updated
- 7 Nov 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
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 1;106(1):64-73. doi: 10.3324/haematol.2019.237693.
PubMed 32054657
Study at a glance
From the registry record, last updated by the sponsor on 7 Nov 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Diagnosis, Discovery and Novel Phenotype Characterisation Using Multimodal Genomics in Patients With Inherited Bone Marrow Failure and Related Disorders (IBMDx Study)
- ClinicalTrials.gov ID
- NCT05196789
- Acronym / sponsor ID
- IBMDx / 77923
- Keywords
- bone marrow failure syndrome, whole genome sequencing, hematological diseases, pancytopenia
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 350 participants (estimated)
- Lead sponsor
- Peter MacCallum Cancer Centre, AustraliaUniversity, hospital or other
- Collaborators
- National Health and Medical Research Council, Australia, University of Melbourne
- Study start
- 18 Mar 2022 (actual)
- Primary completion
- Jun 2025 (estimated)
- Study completion
- Dec 2025 (estimated)
- First posted
- 19 Jan 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Other
- Time perspective
- Prospective
Who may qualify
- Ages
- 3 months and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Patients with suspected IBMFS-RD
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (2 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| whole genome and transcriptome sequencingTo perform whole genome/transcriptome analysis of patients in a cohort of up to 350 Australian patients with IBMFS-RD | Diagnostic test | – |
Primary outcome
Definitive IBMFS-RD diagnosis
Time frame: 3-12 months post baseline
IBMFS-RD diagnosis - An initial analysis of a panel of ~100 genes of established relevance to IBMFS-RD phenotype will be performed on all patients. If no molecular diagnosis is made from the panel of genes, further analysis on the genomic data will be performed using the best practice analytical tools and techniques. All results will be communicated to patients.
5 secondary outcomes
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
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Nov 2024.
- Background: PubMed 32054657Blombery 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 1;106(1):64-73. doi: 10.3324/haematol.2019.237693.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Piers Blombery, MBBS(Hons) contact
Piers Blombery, MBBS(Hons) principal investigator
Peter MacCallum Cancer Centre, Australia
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Inherited BMF Syndrome and Inherited Platelet Disorder, run by Peter MacCallum Cancer Centre, Australia at 1 site in Australia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 7 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Australia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Kelsey Man, PhD (61 3 8559 5000, kelsey.man@petermac.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Definitive IBMFS-RD diagnosis (time frame: 3-12 months post baseline). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05196789, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Nov 2024.