Whole Genome Sequencing for Acute Myeloid Leukemia and Myelodysplastic Syndrome

Recruiting at 1 trial location

Overseen By Meagan Jacoby, M.D., Ph.D.

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Washington University School of Medicine

Disqualifiers: Under 18 years

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

325 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new testing method called ChromoSeq (also known as the Whole Genome Sequencing assay) to determine if it can complement the usual genetic tests for people with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). The goal is to assess whether ChromoSeq can provide more useful information for doctors treating these conditions. Patients who may have AML or MDS and are undergoing genetic testing could be suitable candidates for this trial. As an unphased trial, this study offers patients the chance to contribute to groundbreaking research that could improve future diagnostic methods.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications.

What prior data suggests that the ChromoSeq assay is safe for patients with AML or MDS?

Research shows that ChromoSeq is a tool for studying the entire genetic code of blood-related cancers. Although direct data on its safety is limited, it's crucial to understand that ChromoSeq is a diagnostic test, not a medication or treatment. This means no drugs or medical procedures are required. Instead, it examines DNA from the bone marrow to identify genetic changes.

Whole genome sequencing, like ChromoSeq, is generally considered safe because it doesn't alter anything in the body; it merely analyzes genetic information. Conducted in a controlled lab setting, it resembles other genetic tests used in healthcare. Since ChromoSeq complements standard diagnostic tests, it integrates into regular medical practice without adding safety risks.

In summary, ChromoSeq itself poses no direct safety concerns as it is a non-invasive genetic test. It provides detailed information to help doctors make better decisions about cancer treatment. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about ChromoSeq because it offers a cutting-edge approach to diagnosing and understanding acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). Unlike traditional methods like cytogenetics and FISH, which can be time-consuming and less detailed, ChromoSeq uses whole genome sequencing to provide a comprehensive view of genetic changes in a patient's bone marrow. This could lead to more personalized treatment plans by identifying specific genetic mutations, potentially improving outcomes for patients with these conditions.

What evidence suggests that ChromoSeq is effective for acute myeloid leukemia and myelodysplastic syndrome?

Research shows that ChromoSeq, a test examining a person's entire genetic makeup, quickly and accurately identifies genetic details for patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). In this trial, researchers will perform ChromoSeq on bone marrow DNA from consented patients. Past studies have demonstrated that ChromoSeq helps doctors understand the genetic details of these diseases, guiding them in selecting the best treatments. Compared to standard tests, ChromoSeq might offer a more complete view of the cancer's genetic traits, potentially leading to more personalized and effective treatment plans for patients. ^{6 7 8 9 10}

Who Is on the Research Team?

Meagan Jacoby, M.D., Ph.D.

Principal Investigator

Washington University School of Medicine

Are You a Good Fit for This Trial?

This trial is for adults over 18 with suspected new acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS), who can fill out questionnaires about ChromoSeq. Physicians involved must be treating hematologic malignancies at Washington University and able to request diagnostic testing.

Inclusion Criteria

Requirements for participants to be included in the study.

I am willing and able to fill out questionnaires about ChromoSeq.

You understand what the study is about and agree to sign a form saying that you want to participate.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Genomic Testing

ChromoSeq will be performed on bone marrow DNA from consented patients in parallel with standard genomic testing

15 months

Follow-up

Participants are monitored for safety and effectiveness after genomic testing

63 months

What Are the Treatments Tested in This Trial?

Interventions

• ChromoSeq

Trial Overview The study tests the feasibility of using ChromoSeq, a whole genome sequencing method, alongside standard genomic tests in AML and MDS patients. It aims to understand its practicality through patient data and physician surveys.

How Is the Trial Designed?

Group I: Patients: ChromoSeq Experimental Treatment 1 Intervention

ChromoSeq will be performed on bone marrow DNA from consented patients in parallel with the standard of care cytogenetics, FISH, and the MyeloSeq gene panel obtained from that sample, in a CLIA licensed environment using CLIA-compliant ChromoSeq procedures.

Group II: Stakeholders (Treating Physicians) Active Control 1 Intervention

-Stakeholders (treating physicians) will complete surveys/questionnaires. As of protocol amendment 10/31/2023, the stakeholders (treating physicians) will no longer be completing surveys/questionnaires.

Who Is Running the Clinical Trial?

Washington University School of Medicine

Lead Sponsor

Trials

2,027

Recruited

2,353,000+

Published Research Related to This Trial

The MiSeq next-generation sequencing platform effectively screened 54 cancer-related genes in 63 samples from patients with acute myeloid leukemia, showing complete concordance with results from other established testing methods.

MiSeq demonstrated high accuracy in detecting mutations at low frequencies (as low as 1.5%) and offers advantages such as a quick 4-day turnaround time and the ability to assess both routine and emerging genetic markers, making it a promising tool for clinical applications in monitoring and treating acute myeloid leukemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Next-generation sequencing-based multigene mutational screening for acute myeloid leukemia using MiSeq: applicability for diagnostics and disease monitoring. Luthra, R., Patel, KP., Reddy, NG., et al.[2021]

A new diagnostic approach combining karyotyping and mutational screening using next-generation sequencing allows for rapid and accurate risk stratification in acute myeloid leukemia, significantly speeding up treatment decisions.

In a validation study with 22 patient samples, this method correctly identified 97% of copy number variations and accurately classified all tested karyotypes, demonstrating its potential to enhance subtype-specific therapies for leukemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comprehensive genetic diagnosis of acute myeloid leukemia by next-generation sequencing. Mack, EKM., Marquardt, A., Langer, D., et al.[2020]

Acute myeloid leukemia (AML) shows significant clinical and biological diversity due to distinct chromosome aberrations, which are crucial for diagnosis and risk assessment, but current genetic classifications do not fully capture this complexity.

Recent advancements using genome-wide microarray methods have identified submicroscopic copy number alterations and regions of uniparental disomy in AML, which may enhance classification, prognostication, and understanding of the disease's genetic basis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Array-based cytogenetic approaches in acute myeloid leukemia: clinical impact and biological insights. Bullinger, L., Fröhling, S.[2012]

The Oncomine Myeloid Research (OMR) next-generation sequencing panel demonstrated high accuracy in detecting genetic alterations in myeloid neoplasms, achieving 91.3% concordance for DNA and 100% for RNA samples across a validation set of 77 DNA and 71 RNA samples.

With a clinical sensitivity of 96.7% for DNA and 99.8% for RNA, along with 100% precision and reproducibility, the OMR panel is a reliable tool for diagnosing and understanding the genetic landscape of myeloid neoplasms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Validation of a Myeloid Next-Generation Sequencing Panel for Single-Nucleotide Variants, Insertions/Deletions, and Fusion Genes. Izevbaye, I., Liang, LY., Mather, C., et al.[2021]

Whole-genome sequencing has advanced significantly, allowing for detailed analysis of cancer genomes, particularly in acute myelogenous leukemia (AML), which could lead to more personalized treatment strategies.

As sequencing technology becomes more accessible and affordable, whole-genome sequencing is expected to become a standard part of cancer diagnostics, enhancing our understanding of individual tumors and improving patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Genomics of AML: clinical applications of next-generation sequencing. Welch, JS., Link, DC.[2016]

A new integrative approach using long-read sequencing and high-throughput chromosome capture has identified complex genomic rearrangements in acute myeloid leukemia with complex karyotype (CK-AML), revealing regions with high densities of structural variants that contribute to treatment resistance.

This study introduces the term 'chromocataclysm' to describe focal amplifications near repeat elements that lead to oncogenic fusion transcripts and deregulation of cancer driver genes, highlighting the need for advanced genomic analysis in understanding CK-AML's poor prognosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

AML with complex karyotype: extreme genomic complexity revealed by combined long-read sequencing and Hi-C technology. Klever, MK., Sträng, E., Hetzel, S., et al.[2023]

Recent advancements in genomic characterization of leukemia, particularly acute myeloid leukemia (AML), allow for detailed analysis of genetic mutations, methylation patterns, and RNA expression, enhancing our understanding of the disease.

Integrating data from whole-genome sequencing, methylation analysis, and transcriptome profiling can lead to better-informed treatment strategies and improved patient prognosis in leukemia cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sequencing the AML genome, transcriptome, and epigenome. Mardis, ER.[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]

The LeukoPrint assay, used on bone marrow samples from 137 newly diagnosed AML/MDS patients, showed a 98.1% concordance with traditional cytogenetic methods, indicating its high reliability in detecting copy number aberrations (CNA).

This new method not only improved diagnostic accuracy by redefining risk categories for 16 patients but also provided a more detailed analysis of complex karyotypes, making it a valuable tool for routine cytogenetic assessments in AML/MDS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Whole-genome sequencing as an alternative to analyze copy number abnormalities in acute myeloid leukemia and myelodysplastic syndrome. Lyu, X., Li, T., Zhu, D., et al.[2022]

A study of 112 patients with acute myeloid leukemia (AML) revealed that combining cytogenetic analysis with molecular profiling significantly enhances the ability to predict patient outcomes, allowing for better risk stratification into favorable, intermediate, and unfavorable groups.

Specific mutations, such as CEBPA double mutations and NPM1 without FLT3-ITD, were linked to improved overall survival in patients previously classified as intermediate risk, while mutations in TET2 and others were associated with poorer outcomes, highlighting the importance of molecular profiling in treatment decisions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A targeted next-generation sequencing in the molecular risk stratification of adult acute myeloid leukemia: implications for clinical practice. Lin, PH., Li, HY., Fan, SC., et al.[2022]

The TruSeq Custom Amplicon assay enables the simultaneous sequencing of up to 1536 genetic regions associated with acute leukemias, making it a powerful tool for mutation profiling.

This method allows for efficient analysis of multiple samples (up to 96 per batch) and extensive genomic coverage (up to 650 kb), enhancing the ability to identify mutations that can inform prognosis and treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeted Next-Generation Sequencing of Acute Leukemia. Konnick, E., Lockwood, CM., Wu, D.[2018]

Citations

1. nejm.org nejm.org/doi/full/10.1056/NEJMoa2024534

Genome Sequencing as an Alternative to Cytogenetic ... We found that whole-genome sequencing provided rapid and accurate genomic profiling in patients with AML or MDS.

2. centerwatch.com centerwatch.com/clinical-trials/listings/NCT04986657/whole-genome-sequencing-chromoseq-as-an-adjunct-to-conventional-genomic-profiling-in-aml-and-mds

Whole Genome Sequencing (ChromoSeq) as an Adjunct to ... This is a single institution, prospective study of the whole genome sequencing assay, ChromoSeq. Using prospectively collected patient data, ...

3. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs000159.v4.p2

Whole-Genome Sequencing of Acute Myeloid Leukemia - NCBI We used massively parallel sequencing technology to sequence the genomic DNA of tumor cells (leukemic bone marrow) and normal cells (skin biopsy) obtained ...

4. haematologica.org haematologica.org/article/view/haematol.2023.284947

Genome sequencing in the management of ... Myelodysplastic syndrome/acute myeloid leukemia. The ICC of myeloid neoplasms and acute leukemia has introduced the new category of MDS/AML.

5. cancer.gov cancer.gov/news-events/cancer-currents-blog/2021/whole-genome-sequencing-guides-treatment-aml-mds

Whole-Genome Sequencing Could Help Guide AML, MDS ... Researchers are studying whether whole-genome sequencing can help doctors select the best treatments for people with acute myeloid leukemia and myelodysplastic ...

6. pathologyservices.wustl.edu pathologyservices.wustl.edu/genomic-and-molecular-pathology/oncology-testing/chromoseq/

ChromoSeq - St. Louis ChromoSeq is a whole genome sequencing (WGS) assay intended for the comprehensive clinical genomic evaluation of known or suspected hematologic neoplasms ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10088148/

Whole-genome sequencing identifies novel predictors for ... Mutations in two novel genes, CHD1 and DDX11, demonstrated a negative impact on survival in AML/MDS and lymphoid cancer data from the Cancer ...

8. ashpublications.org ashpublications.org/blood/article/140/21/2228/486675/Genomic-profiling-for-clinical-decision-making-in

Genomic profiling for clinical decision making in myeloid ... Broad genomic sequencing assays allow for the detection of genomic alterations anywhere in the coding genome (WES, interrogating 1%-2% of the whole genome) or ...

9. illumina.com illumina.com/science/genomics-research/articles/hematologic-malignancies.html

Applications of whole-genome sequencing in hematologic ... Safety Data Sheets · Share Desktop · For every ... Other myeloid malignancies, like acute myeloid leukemia (AML) and myelodysplastic syndrome ...

10. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1875918115001208

Genetic Testing in Acute Myeloid Leukemia and ... Translocations between genes (gene rearrangements) are detected most commonly by conventional karyotyping, FISH, and RT-PCR, and, more recently, by NGS assays.