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

Trial Summary

What is the purpose of this trial?

This clinical trial tests next generation sequencing (NGS) for the detection of precursor features of pre-myeloid cancers and bone marrow failure syndromes. NGS is a procedure that looks at relevant cancer associated genes and what they do. Finding genetic markers for pre-malignant conditions may help identify patients who are at risk of pre-myeloid cancers and bone marrow failure syndromes and lead to earlier intervention.

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 data supports the effectiveness of this treatment for early detection of myeloid leukemia or bone marrow failure syndrome?

Next-generation sequencing (NGS) is effective in identifying genetic changes in myeloid disorders, which helps in diagnosing and managing these conditions. Studies show that NGS can detect a high percentage of genetic variants, improving diagnosis and treatment decisions for patients with myeloid neoplasms. ^{1 2 3 4 5}

Is genomic testing using next-generation sequencing (NGS) safe for humans?

The research does not specifically address safety concerns related to genomic testing using next-generation sequencing (NGS) in humans, but it is widely used in clinical settings for diagnosing and monitoring myeloid disorders, suggesting it is generally considered safe. ^{1 4 6 7 8}

How is genomic testing different from other treatments for early detection of myeloid leukemia or bone marrow failure syndrome?

Genomic testing, using next-generation sequencing (NGS), is unique because it analyzes genetic mutations to help diagnose, assess risk, and monitor disease progression in myeloid disorders. Unlike traditional treatments, it provides a detailed genetic profile that can guide personalized treatment decisions and detect minimal residual disease, offering a more precise approach to managing these conditions. ^{1 4 5 7 9}

Research Team

Mrinal Patnaik, MBBS

Principal Investigator

Mayo Clinic

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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) 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]

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]

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]

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) 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]

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 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]

References

1. United States 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. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

Next-generation sequencing-based panel testing for myeloid neoplasms. [2018]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Next-Generation Sequencing Improves Diagnosis, Prognosis and Clinical Management of Myeloid Neoplasms. [2020]

4. England pubmed.ncbi.nlm.nih.gov

Design, implementation and clinical utility of next generation sequencing in myeloid malignancies: acute myeloid leukaemia and myelodysplastic syndrome. [2021]

5. New Zealand 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. [2021]

6. England pubmed.ncbi.nlm.nih.gov

Genomic testing in myeloid malignancy. [2019]

7. Switzerland 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. [2023]

8. United States pubmed.ncbi.nlm.nih.gov

Ultra-Rapid Reporting of GENomic Targets (URGENTseq): Clinical Next-Generation Sequencing Results within 48 Hours of Sample Collection. [2021]

9. United States pubmed.ncbi.nlm.nih.gov

Next-generation sequencing for minimal residual disease monitoring in acute myeloid leukemia patients with FLT3-ITD or NPM1 mutations. [2021]