ChromoSeq for Myelodysplastic Syndrome

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

Trial Summary

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 data supports the effectiveness of the treatment ChromoSeq for Myelodysplastic Syndrome?

The research suggests that whole genome sequencing (WGS) and similar genomic profiling methods can effectively detect genetic abnormalities in myelodysplastic syndromes (MDS), often with higher sensitivity and success rates than traditional methods. This indicates that ChromoSeq, which involves WGS, may be a valuable tool for diagnosing and assessing the prognosis of MDS by identifying important genetic changes. ^{1 2 3 4 5}

Is ChromoSeq safe for humans?

The research articles provided do not contain specific safety data for ChromoSeq or related whole genome sequencing assays in humans. ^{4 5 6 7 8}

How does the ChromoSeq treatment differ from other treatments for myelodysplastic syndrome?

ChromoSeq is unique because it uses next-generation sequencing (NGS) to detect both gene mutations and large chromosomal abnormalities in myelodysplastic syndromes (MDS), offering a more comprehensive and sensitive analysis compared to traditional cytogenetic methods. This approach improves diagnosis and risk assessment by identifying genetic changes that might be missed by conventional techniques. ^{1 4 5 9 10}

What is the purpose of this trial?

This is a single institution, prospective study of the whole genome sequencing assay, ChromoSeq. Using prospectively collected patient data, coupled with physician surveys, the investigators seek to determine the feasibility of implementing ChromoSeq in addition to standard genomic testing, for patients with the diagnosis of myelodysplastic syndrome (MDS).

Research Team

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

Principal Investigator

Washington University School of Medicine

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

References

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

Impact of copy neutral loss of heterozygosity and total genome aberrations on survival in myelodysplastic syndrome. [2023]

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

Genomic array as compared to karyotyping in myelodysplastic syndromes in a prospective clinical trial. [2018]

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

The effectiveness of high-resolution-comparative genomic hybridization in detecting the most common chromosomal abnormalities in pediatric myelodysplastic syndromes. [2006]

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

Shallow whole-genome sequencing of bone marrow aspirates in myelodysplastic neoplasms: A retrospective comparison with cytogenetics. [2023]

5. Switzerland 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. [2021]

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

Prevalence and prognostic significance of allelic imbalance by single-nucleotide polymorphism analysis in low-risk myelodysplastic syndromes. [2021]

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

The importance of subclonal genetic events in MDS. [2022]

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

Microarray-based comparative genomic hybridization of cancer targets reveals novel, recurrent genetic aberrations in the myelodysplastic syndromes. [2022]

9. Czech Republic pubmed.ncbi.nlm.nih.gov

The assessment of array comparative genomic hybridization in complex karyotype analyses. [2022]

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

The use of cytogenetic microarrays in myelodysplastic syndrome characterization. [2013]