ChromoSeq for 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: Younger than 18

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

Duration: 24 months

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether a new test called ChromoSeq (a Whole Genome Sequencing assay) can complement current genetic tests for people with myelodysplastic syndrome (MDS), a bone marrow disorder. Researchers aim to determine if ChromoSeq enhances the diagnosis and management of MDS. Patients with a confirmed or suspected diagnosis of MDS who have not received certain treatments might be suitable for this study. As an unphased trial, it offers patients the chance to contribute to groundbreaking research that could improve future diagnostic and management strategies for MDS.

Do I need to stop my current medications for the ChromoSeq trial?

The trial information does not specify whether you need to stop taking your current medications. However, it mentions that patients who have received certain treatments like transfusional support or erythropoietin-stimulating agents are eligible, suggesting that some medications may be allowed.

What prior data suggests that ChromoSeq is safe for patients with myelodysplastic syndrome?

Research shows that ChromoSeq, a tool for whole genome sequencing, is under evaluation to determine if it can enhance the diagnosis of myelodysplastic syndrome (MDS). Researchers are studying this tool to see if it can uncover new genetic details that might improve understanding of MDS.

In terms of safety, ChromoSeq is a genetic test, not a medication or physical treatment, so it doesn't pose the same risks as a new drug. Studies have not reported any negative effects from using ChromoSeq, as it involves analyzing DNA from blood or bone marrow samples. This makes it generally safe for patients, similar to other genetic tests already in use. ^{1 2 3 4 5}

Why are researchers excited about this trial?

ChromoSeq is unique because it uses advanced genetic sequencing techniques to analyze DNA from bone marrow or blood samples of patients with myelodysplastic syndrome. Unlike standard options like cytogenetics and FISH, which look for changes in chromosomes, ChromoSeq provides a more comprehensive view by identifying genetic mutations at a deeper level. Researchers are excited about this because it could lead to more precise diagnoses and personalized treatment plans, potentially improving outcomes for patients.

What evidence suggests that ChromoSeq is effective for myelodysplastic syndrome?

Research has shown that whole genome sequencing, such as ChromoSeq, can quickly and accurately analyze the genes of patients with myelodysplastic syndrome (MDS). In this trial, researchers will perform ChromoSeq on bone marrow or peripheral blood DNA from consented patients. Studies have found that this sequencing method greatly enhances doctors' ability to diagnose and understand MDS, helping them identify specific forms of the disease. This enables doctors to customize treatments more effectively for each patient. Additionally, genomic profiling with ChromoSeq offers a more detailed genetic picture than traditional methods, potentially leading to better treatment choices and improved patient outcomes. ^{1 6 7 8 9}

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 with Myelodysplastic Syndrome (MDS) or suspected MDS at Washington University School of Medicine. Participants must be willing to complete surveys about ChromoSeq, have not had disease-modifying treatments, and can sign a consent form. Those who've only had supportive treatments like transfusions or growth factors are eligible.

Inclusion Criteria

I am diagnosed with MDS or suspected to have MDS, and tests are planned.

I haven't taken any drugs like lenalidomide for my condition.

You receive medical care as an outpatient rather than staying in the hospital.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

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

24 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 month

What Are the Treatments Tested in This Trial?

Interventions

• ChromoSeq

Trial Overview The study tests the use of Whole Genome Sequencing (ChromoSeq) alongside standard genomic testing in patients with MDS. It aims to assess how feasible it is to add this new test into routine care by collecting data and physician feedback.

How Is the Trial Designed?

Group I: Patients: ChromSeq Experimental Treatment 1 Intervention

ChromoSeq will be performed on bone marrow or peripheral blood 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

Who Is Running the Clinical Trial?

Washington University School of Medicine

Lead Sponsor

Trials

2,027

Recruited

2,353,000+

Edward P. Evans Foundation

Collaborator

Trials

2

Recruited

2,100+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

American Society of Hematology

Collaborator

Trials

14

Recruited

20,800+

Published Research Related to This Trial

High-resolution comparative genomic hybridization (HR-CGH) was able to detect DNA copy number alterations in 8 out of 9 samples from patients with myelodysplastic syndromes (MDS) and acute myelogenous leukemia (AML), demonstrating its effectiveness in identifying chromosomal imbalances.

HR-CGH revealed additional genetic changes not detected by conventional cytogenetics in 3 bone marrow samples, highlighting its superior sensitivity and specificity for diagnosing these blood disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effectiveness of high-resolution-comparative genomic hybridization in detecting the most common chromosomal abnormalities in pediatric myelodysplastic syndromes. Babicz, M., Kowalczyk, JR., Winnicka, D., et al.[2006]

A new targeted next-generation sequencing (NGS) assay was developed to detect genetic alterations in myelodysplastic syndromes (MDS) and related disorders, showing about 97% concordance with traditional karyotyping and SNP arrays in a large patient cohort.

This NGS platform not only matches the sensitivity of SNP arrays but also surpasses conventional cytogenetics, allowing for better identification of genetic changes that can improve diagnosis and risk assessment in patients with MDS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Single-Run Next-Generation Sequencing (NGS) Assay for the Simultaneous Detection of Both Gene Mutations and Large Chromosomal Abnormalities in Patients with Myelodysplastic Syndromes (MDS) and Related Myeloid Neoplasms. Liquori, A., Lesende, I., Palomo, L., et al.[2021]

Shallow whole genome sequencing (sWGS) successfully detected copy number alterations (CNAs) in all 33 bone marrow samples from patients with myelodysplastic neoplasms (MDS), including three cases where conventional cytogenetic analysis (CCA) failed.

The prognostic stratification of patients using sWGS was consistent with CCA in 27 out of 30 cases, suggesting that sWGS is a reliable and cost-efficient alternative to CCA for routine diagnostics in MDS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Shallow whole-genome sequencing of bone marrow aspirates in myelodysplastic neoplasms: A retrospective comparison with cytogenetics. Rengifo, LY., Smits, S., Boeckx, N., et al.[2023]

In a study of 119 low-risk myelodysplastic syndrome (MDS) patients, SNP microarray analysis revealed uniparental disomy (UPD) in 46% of cases, along with deletions and amplifications, indicating previously undetected genomic abnormalities that could influence treatment decisions.

The presence of deletions and the International Prognostic Scoring System (IPSS) scores were correlated with overall survival, suggesting that SNP microarray findings could help stratify patients for early therapeutic interventions, although only IPSS scores remained significant in multivariate analysis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prevalence and prognostic significance of allelic imbalance by single-nucleotide polymorphism analysis in low-risk myelodysplastic syndromes. Mohamedali, A., Gäken, J., Twine, NA., et al.[2021]

This study represents the largest targeted sequencing effort in myelodysplastic syndrome (MDS), analyzing 738 patients, including 603 specifically diagnosed with MDS.

The research focused on sequencing 111 genes, which may provide valuable insights into the genetic factors contributing to MDS and potentially guide future treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The importance of subclonal genetic events in MDS. Bejar, R., Abdel-Wahab, O.[2022]

Oligo/SNP-based genomic array profiling is more effective than traditional karyotyping in identifying genetic abnormalities in myelodysplastic syndrome (MDS), detecting 55 abnormal cases compared to 35 found by karyotyping in a study of 104 patients.

This advanced profiling method not only confirmed most cytogenetic lesions identified by karyotyping but also revealed additional genetic abnormalities that could be clinically significant, including 26 cases of cytogenetic invisible abnormalities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Genomic array as compared to karyotyping in myelodysplastic syndromes in a prospective clinical trial. Stevens-Kroef, MJ., Olde Weghuis, D., ElIdrissi-Zaynoun, N., et al.[2018]

In a study of 68 myelodysplastic syndrome (MDS) patients, 73% had abnormal results from chromosomal genetic array testing (CGAT), highlighting its potential as a valuable diagnostic tool for identifying underlying genetic issues in MDS.

Patients with higher Total Genomic Aberration (TGA) scores had significantly lower overall survival rates, indicating that CGAT can not only improve diagnostics but also provide important prognostic information regarding patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of copy neutral loss of heterozygosity and total genome aberrations on survival in myelodysplastic syndrome. Yeung, CCS., McElhone, S., Chen, XY., et al.[2023]

High-resolution microarray analysis of 35 myelodysplastic syndrome (MDS) samples revealed clinically relevant copy number aberrations (CNAs) in all samples, with 80% showing new cytogenetic aberrations not detected by traditional methods like karyotyping.

The study identified 132 cryptic aberrations in 71.4% of cases, including deletions of key genes associated with hematologic cancers, highlighting the potential of microarray technology to uncover significant genetic changes that could influence disease progression and treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Microarray-based comparative genomic hybridization of cancer targets reveals novel, recurrent genetic aberrations in the myelodysplastic syndromes. Kolquist, KA., Schultz, RA., Furrow, A., et al.[2022]

The study analyzed 12 bone marrow samples from patients with myelodysplastic syndromes (MDS) using advanced molecular-cytogenetic methods, revealing complex genome rearrangements and improving the understanding of these malignancies.

Array comparative genomic hybridization (aCGH) detected 14 additional chromosomal changes beyond those identified by traditional methods, demonstrating its higher resolution and effectiveness in characterizing unbalanced chromosomal aberrations in MDS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The assessment of array comparative genomic hybridization in complex karyotype analyses. Bystřická, D., Zemanová, Z., Březinová, J., et al.[2022]

Microarray platforms, especially SNP arrays, provide valuable diagnostic and prognostic information for patients with myelodysplastic syndromes (MDS), detecting genomic changes that can influence treatment outcomes.

SNP karyotyping can improve prognostic stratification, as patients identified with adverse-risk chromosomal findings after array testing have been linked to poorer survival rates, highlighting the importance of these tests in guiding therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The use of cytogenetic microarrays in myelodysplastic syndrome characterization. Shaffer, LG., Ballif, BC., Schultz, RA.[2013]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05434598

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, coupled with ...

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

Genome sequencing in the management of ... Genomic profiling can significantly improve the diagnostic approach to MDS, allowing the identification of distinct nosological entities such as ...

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

Genome Sequencing as an Alternative to Cytogenetic ... In our study, we found that whole-genome sequencing provided rapid and accurate genomic profiling in patients with AML or MDS. Such sequencing ...

4. 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 ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11788631/

Genome sequencing in the management of ... Genomic profiling can significantly improve the diagnostic approach to MDS, allowing the identification of distinct nosological entities.

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

Whole-genome sequencing identifies novel predictors for ... Whole-genome sequencing identifies novel predictors for hematopoietic cell transplant outcomes for patients with myelodysplastic syndrome: a ...

7. 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.

8. nature.com nature.com/articles/s41375-022-01652-8

High-resolution structural variant profiling of ... The findings showed the lack of the current standard-of-care workflow to comprehensively evaluate the genomic landscape of MDS and provided ...

9. ashpublications.org ashpublications.org/blood/article/146/16/1883/546479/A-precision-medicine-approach-to-the

A precision medicine approach to the myelodysplastic ... The deletion of the long arm of chromosome 5 or the loss of the whole chromosome 5 are common occurrences in myeloid neoplasms, including MDS, ...