Genomic Studies for Early Detection of Myeloid Leukemia or Bone Marrow Failure Syndrome

Recruiting at 3 trial locations

Overseen By Dani Rud

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Mayo Clinic

Disqualifiers: Under 18 years

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

2000 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a genetic method called next-generation sequencing (NGS) to detect early signs of potential blood cancers and bone marrow problems. The goal is to identify genetic markers that might appear before these conditions fully develop, allowing for earlier intervention. Participants will provide samples, such as blood or saliva, for analysis and may receive genetic counseling. This trial suits individuals with unexplained blood cell issues, certain inherited syndromes linked to blood cancers, or those with family members who have these conditions. As an unphased study, this trial offers a unique opportunity to contribute to groundbreaking research that could lead to earlier detection and intervention for blood-related conditions.

Do I need to stop my current medications for this trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What prior data suggests that genomic testing is safe for detecting precursor features of pre-myeloid cancers and bone marrow failure syndromes?

Research has shown that next-generation sequencing (NGS) is generally safe for identifying genetic markers related to bone marrow conditions. Studies using NGS have found that it can detect genetic mutations without causing significant side effects.

For example, researchers have used NGS to diagnose inherited bone marrow failure syndromes, and these studies did not report any major safety concerns or adverse events related to the procedure itself. This indicates that the process of collecting samples and analyzing them with NGS is well-tolerated by patients.

While NGS is not a treatment in the usual sense—it's more like a very detailed test—it doesn't involve taking medications or undergoing invasive procedures beyond giving blood samples or biopsies. This reduces the risk of side effects compared to other medical treatments.

Based on current research, NGS appears to be a safe and effective tool for detecting genetic changes linked to early-stage bone marrow cancers and failure syndromes. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about genomic testing for early detection of myeloid leukemia or bone marrow failure syndrome because it represents a major shift from traditional diagnostic methods. Unlike conventional approaches that often rely on symptoms or routine blood tests, genomic testing dives deep into the DNA of cells to uncover potential issues before symptoms even appear. This method uses next-generation sequencing (NGS) to analyze genetic material from blood, bone marrow, or other tissues, offering a more personalized and accurate way to catch these conditions early. By identifying genetic markers associated with these diseases, genomic testing could lead to earlier interventions and more tailored treatment plans, potentially improving patient outcomes significantly.

What evidence suggests that genomic testing is effective for early detection of myeloid leukemia or bone marrow failure syndrome?

Research shows that next-generation sequencing (NGS), which participants in this trial will undergo, can identify genetic markers related to early-stage blood cancers and bone marrow problems. Studies have demonstrated that NGS can detect numerous genetic mutations and provide detailed information about these changes. This technology proves particularly useful for diagnosing genetic blood disorders in young patients. NGS also reveals the genetic makeup of acute myeloid leukemia (AML), aiding in understanding the disease's development. Early findings suggest that using NGS for genetic testing might detect issues sooner, potentially leading to earlier treatment. ^{3 6 7 8 9}

Who Is on the Research Team?

Mrinal Patnaik, MBBS

Principal Investigator

Mayo Clinic

Are You a Good Fit for This Trial?

This study is for individuals with early signs of myeloid cancers or inherited bone marrow failure syndromes. It includes those with clonal hematopoiesis, age-related changes in blood cells, unclear cytopenias, and low-risk Myelodysplastic Syndromes. People who can't understand or sign the consent form are excluded.

Inclusion Criteria

I have a bone marrow failure syndrome with a risk for blood cancer.

I have age-related changes in my blood cells.

I have been diagnosed with ICUS.

Exclusion Criteria

I am able to understand and sign the Informed Consent Form.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Biospecimen Collection and NGS Analysis

Participants undergo blood sample collection, bone marrow biopsy, skin punch biopsy, hair follicle collection, buccal swab, and/or saliva collection for NGS analysis. Patients may also receive genetic counseling.

Ongoing

Multiple visits as needed

Follow-up

Participants are monitored for the occurrence of cytopenias, myelodysplastic syndrome (MDS), and acute myeloid leukemia (AML) over the course of the study

Up to 5 years

What Are the Treatments Tested in This Trial?

Interventions

• Follow-up
• Genomic Testing

Trial Overview The trial is focused on monitoring patients using genomic studies to identify and diagnose precursor conditions to myeloid neoplasms and inherited bone marrow failures. There's no specific medication being tested; it's more about follow-up studies.

How Is the Trial Designed?

Group I: Screening (biospecimen collection, NGS analysis) Experimental Treatment 8 Interventions

Participants may undergo blood sample collection, a bone marrow biopsy, a skin punch biopsy, hair follicle collection, a buccal swab, and/or saliva collection for NGS analysis on study. Patients may additionally undergo clinical assessment and may receive genetic counseling on study.

Genomic Testing is already approved in United States, European Union for the following indications:

Approved in United States as Next Generation Sequencing for:

• Pre-myeloid cancers
• Bone marrow failure syndromes

Approved in European Union as Next Generation Sequencing for:

• Pre-myeloid cancers
• Bone marrow failure syndromes
• Hematological disorders

Who Is Running the Clinical Trial?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

Published Research Related to This Trial

The URGENTseq platform allows for rapid genomic testing of multiple genes in patients with hematologic malignancies, providing results within 48 hours, which is crucial for timely treatment decisions in aggressive diseases like acute myeloid leukemia.

Validation of URGENTseq showed 100% concordance with conventional sequencing methods, ensuring reliable detection of mutations that guide therapy, including key genes like CALR, JAK2, and IDH1.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ultra-Rapid Reporting of GENomic Targets (URGENTseq): Clinical Next-Generation Sequencing Results within 48 Hours of Sample Collection. Patel, KP., Ruiz-Cordero, R., Chen, W., et al.[2021]

Next-generation sequencing (NGS) has greatly enhanced our ability to detect genetic alterations in myeloid neoplasms, providing crucial information beyond traditional diagnostic methods like morphologic examination and cytogenetics.

With the availability of numerous myeloid-focused NGS panels, faster turnaround times, and decreasing costs, NGS is expected to significantly impact the management and treatment of patients with myeloid neoplasms in the near future.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Next-generation sequencing-based panel testing for myeloid neoplasms. Kuo, FC., Dong, F.[2018]

Custom data filtering in the Oncomine Myeloid Research Assay identified 96 reportable variants, including 26 clinically significant mutations, that were missed by the default filter, highlighting the importance of tailored analysis in variant detection.

The newly introduced Oncomine 5.14 extended filter algorithm improves detection of clinically relevant mutations but does not capture all significant variants, indicating that supplementary methods like fragment analysis for specific mutations can enhance diagnostic accuracy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improved Variant Detection in Clinical Myeloid NGS Testing by Supplementing a Commercial Myeloid NGS Assay with Custom or Extended Data Filtering and Accessory Fragment Analysis. Schejbel, L., Novotny, GW., Breinholt, MF., et al.[2021]

The Oncomine Myeloid Assay GX panel on the Ion Torrent Genexus platform successfully identified 100% of control genetic variants and achieved an 80% detection rate for clinically relevant DNA and RNA alterations in real patient samples, demonstrating its efficacy in diagnosing myeloid neoplasms.

This integrated next-generation sequencing system not only streamlines the testing process but also has the potential to accelerate the time to precision therapies by providing rapid and accurate genetic information for treatment decisions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rapid and Automated Semiconductor-Based Next-Generation Sequencing for Simultaneous Detection of Somatic DNA and RNA Aberrations in Myeloid Neoplasms. Sande, CM., Wu, R., Yang, G., et al.[2023]

Next-generation sequencing (NGS) was used to analyze samples from 121 patients with myeloid neoplasms, detecting 278 pathogenic variants in 84% of patients, which significantly improved genetic characterization compared to traditional methods.

The use of NGS not only changed the diagnosis for seven patients and the prognosis for 15 but also identified 44 candidates for clinical trials, highlighting its potential to tailor treatments more effectively for individual patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Next-Generation Sequencing Improves Diagnosis, Prognosis and Clinical Management of Myeloid Neoplasms. Carbonell, D., Suárez-González, J., Chicano, M., et al.[2020]

Next generation sequencing (NGS) is crucial for understanding myeloid malignancies like acute myeloid leukaemia (AML) and myelodysplastic syndrome (MDS), as it helps in diagnosing, assessing prognosis, and identifying treatment targets.

Despite its benefits, NGS presents technical challenges that require expert interpretation to differentiate between clinically relevant mutations and benign variants, making it essential for effective patient management in hematological disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Design, implementation and clinical utility of next generation sequencing in myeloid malignancies: acute myeloid leukaemia and myelodysplastic syndrome. Hughes, CFM., Gallipoli, P., Agarwal, R.[2021]

Next generation sequencing (NGS) of peripheral blood samples shows a very strong correlation with bone marrow samples in diagnosing and monitoring myeloid neoplasias, with a high concordance rate of 99.6% and sensitivity of 98.8%.

This study indicates that peripheral blood can be a reliable surrogate for bone marrow evaluations in myeloid neoplasms, allowing for effective molecular classification without compromising diagnostic accuracy, even in patients without circulating blasts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Myeloid NGS Analyses of Paired Samples from Bone Marrow and Peripheral Blood Yield Concordant Results: A Prospective Cohort Analysis of the AGMT Study Group. Jansko-Gadermeir, B., Leisch, M., Gassner, FJ., et al.[2023]

Next-generation sequencing (NGS) is transforming clinical genetic testing for myeloid malignancies by allowing for a broader analysis of genetic alterations compared to traditional cytogenetics and single-gene testing.

While NGS can provide valuable insights into genetic changes associated with diseases, it also presents challenges such as managing incidental findings and understanding germ line variations, which need to be carefully considered in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Genomic testing in myeloid malignancy. Docking, TR., Karsan, A.[2019]

Next-generation sequencing (NGS) has been evaluated as a reliable method for assessing minimal residual disease (MRD) in acute myeloid leukemia (AML) patients, analyzing 80 samples and providing detailed insights into clonal sequences and allelic ratios.

NGS showed a high concordance rate of 95% with traditional methods in detecting MRD in NPM1 mutated patients, demonstrating its effectiveness and flexibility as a tool for monitoring leukemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Next-generation sequencing for minimal residual disease monitoring in acute myeloid leukemia patients with FLT3-ITD or NPM1 mutations. Thol, F., Kölking, B., Damm, F., et al.[2021]

Citations

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Myeloid NGS Analyses of Paired Samples from Bone Marrow ... Our results clearly show, in a prospective setting, that sequential molecular analyses of peripheral blood specimens can be reliably used to ...

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1756231725001331

Genetic testing of bone marrow: the what, the when and ... NGS not only enables simultaneous profiling of multiple actionable mutations but also provides information about structural variants (SVs), copy ...

3. link.springer.com link.springer.com/article/10.1007/s00277-025-06392-0

Clinical usefulness of next-generation sequencing-based ... This study demonstrated the diagnostic usefulness of NGS-based target gene sequencing for pediatric and AYA patients with suspected genetic hematologic ...

4. haematologica.org haematologica.org/article/view/12156/78573

Serial next-generation sequencing for detecting germline ... ... next-generation sequencing (NGS) have significantly deepened our understanding of the genomic landscape of acute myeloid leukemia (AML),.

5. nature.com nature.com/articles/gim2016197

Clinical utility of next-generation sequencing for inherited ... We achieved successful genetic diagnoses for 53 of 121 patients (44%) using targeted sequencing and for 68 of 250 patients (27%) using WES. In ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12141389/

Clinical usefulness of next-generation sequencing-based ... Clinical usefulness of next-generation sequencing-based target gene sequencing in diagnosis of inherited bone marrow failure syndrome

7. ashpublications.org ashpublications.org/blood/article/141/13/1513/493846/Predisposition-to-myeloid-malignancies-in

Predisposition to myeloid malignancies in Shwachman ... Genomic analysis revealed that most myeloid malignancies in patients with SDS have biallelic loss-of-function TP53 mutations. Single-cell DNA ...

8. cincinnatichildrens.org cincinnatichildrens.org/-/media/Cincinnati-Childrens/Home/service/d/dchi/default/IM-5001_3-13-Bone-Marrow-Failure-Syndromes.pdf

Bone Marrow Failure Gene Sequencing Panel This panel is specifically designed to diagnose the most common genetic causes of bone marrow failure including dyskeratosis congenita, Diamond Blackfan anemia, ...

9. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6406956/

Next Generation Sequencing in AML—On the Way to ... Our aim is to provide a concise summary of current evidence regarding the relevance of NGS for the diagnosis, risk stratification, treatment planning and ...