Whole Genome Sequencing (ChromoSeq) as an Adjunct to Conventional Genomic Profiling in AML and MDS

A Prospective Study of Whole Genome Sequencing (ChromoSeq) as an Adjunct to Conventional Genomic Profiling in AML and MDS

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 diagnoses of acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS).

Study Overview

• Status: Recruiting
• Conditions: Acute Myeloid Leukemia; Myelodysplastic Syndromes; Whole Genome Sequencing
• Intervention / Treatment: Device: ChromoSeq

• Study Type: Interventional
• Enrollment (Estimated): 325
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Meagan Jacoby, M.D., Ph.D.; Phone Number: 314-747-8439; Email: mjacoby@wustl.edu

Study Locations

• United States
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Recruiting
      • Washington University School of Medicine
      • Sub-Investigator: Mary Politi, Ph.D.
      • Contact: Meagan Jacoby, M.D., Ph.D.; Phone Number: 314-747-8439; Email: mjacoby@wustl.edu
      • Sub-Investigator: Feng Gao, Ph.D.
      • Sub-Investigator: David Spencer, M.D., Ph.D.
      • Principal Investigator: Meagan Jacoby, M.D., Ph.D.
      • Sub-Investigator: Timothy Ley, M.D.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria Patient

• Patient with a clinical suspicion for a new diagnosis of AML or MDS for whom the diagnostic molecular testing via the hematologic molecular algorithm (HMA) at BJH is requested or planned to be requested.
• Adult patients 18 years or older.
• Ability to understand and willingness to sign an IRB approved written informed consent document.

Inclusion Criteria Physician

• Treating physician at Washington University School of Medicine who directs therapy for individuals with hematologic malignancies.
• Able and willing to complete standardized questionnaires about usability, and stakeholder perceptions of ChromoSeq during the ChromoSeq implementation process.

Exclusion Criteria Patient

• Younger than 18 years of age

Exclusion Criteria Physician

• Does not treat patients at Washington University School of Medicine

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Patients: ChromoSeq; 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.	Device: ChromoSeq; Novel, streamlined whole genome sequencing approach
No Intervention: Stakeholders (Treating Physicians); -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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sensitivity of ChromoSeq as measured by total number of recurrent structural variants identified	As compared to conventional cytogenetics in a real-time clinical setting; The total number of recurrent structural variants will be measured in each sample by ChromoSeq and metaphase cytogenetics yielding a pair of measurements. Each measurement will also be dichotomized into the presence or absence of at least one recurrent structural variant. The hypothesis of no difference in the number of variants detected by each method will be analyzed by a paired-sample t-test. However, if it is determined that the assumptions of a t-test are not tenable then a paired-sample sign test will be used instead. McNemar's test will be used to compare whether or not at least one recurrent structural variant identified is by each method.	Through completion of all ChromoSeq tests (estimated to be 15 months)
Sensitivity of ChromoSeq as measured by total number of copy number alterations identified	As compared to conventional cytogenetics in a real-time clinical setting; The total number of copy number alterations will be measured in each sample by ChromoSeq and metaphase cytogenetics yielding a pair of measurements. Each measurement will also be dichotomized into the presence or absence of at least one copy number alteration. The hypothesis of no difference in the number of copy number alterations detected by each method will be analyzed by a paired-sample t-test. However, if it is determined that the assumptions of a t-test are not tenable then a paired-sample sign test will be used instead. McNemar's test will be used to compare whether or not at least one copy number alterations is identified is by each method.	Through completion of all ChromoSeq tests (estimated to be 15 months)
Sensitivity of ChromoSeq as measured by number of single nucleotide variants identified	As compared to high coverage gene panels in a real-time clinical setting; The number of single nucleotide variants will be counted for each sample. Additionally, the data will be dichotomized into the presence or absence of at least one single nucleotide variant. Data will be analyzed by paired-sample t-tests and McNemar's test.	Through completion of all ChromoSeq tests (estimated to be 15 months)
Sensitivity of ChromoSeq as measured by number of insertion-deletions identified	As compared to high coverage gene panels in a real-time clinical setting; The number of insertion-deletions will be counted for each sample. Additionally, the data will be dichotomized into the presence or absence of at least one insertion-deletion. Data will be analyzed by paired-sample t-tests and McNemar's test.	Through completion of all ChromoSeq tests (estimated to be 15 months)
Determine if risk-stratification using ChromoSeq correlates with overall-survival	As compared to metaphase cytogenetics; The relationship of risk-stratification defined by either ChromoSeq or conventional cytogenetics to clinical outcome will be illustrated with Kaplan-Meier survival analyses on overall survival for both ChromoSeq and metaphase cytogenetics. The predictive accuracy of the two methods will be tested by comparing the area under the ROC curves using the method of DeLong et al.	Through completion of follow-up for all patients (estimated to be 63 months)
Determine if risk-stratification using ChromoSeq correlates with event-free survival	As compared to metaphase cytogenetics; The relationship of risk-stratification defined by either ChromoSeq or conventional cytogenetics to clinical outcome will be illustrated with Kaplan-Meier survival analyses on event-free survival for both ChromoSeq and metaphase cytogenetics. The predictive accuracy of the two methods will be tested by comparing the area under the ROC curves using the method of DeLong et al.	Through completion of follow-up for all patients (estimated to be 63 months)
Proportion of cases in which ChromoSeq provides new genetic information to the clinician	As compared to conventional genomic profiling (cytogenetics, FISH, and next-generation sequencing) that is used for clinical management (such as risk-stratification or institution of targeted gene therapy); Items in the ChromoSeq Implementation Physician Survey will be used to describe physician evaluation of ChromoSeq with conventional genomic profiling with regard to clinical management. Responses to these items will be presented in frequency tables. For statistical analysis, the values of each item will be recoded from 1-5 to -2 to +2 and one-sample t-tests used to test the null hypothesis that the mean value is 0 (neither agree nor disagree.) In addition, case-reports will be reviewed for qualitative evaluations of physician experience with the two methods.	Through completion of all ChromoSeq tests (estimated to be 15 months)
ChromoSeq turnaround time	-Measured from time of order requisition (hematologic molecular algorithm from Barnes Jewish Hospital) to return of report to the medical record	Through completion of all ChromoSeq tests (estimated to be 15 months)
Proportion of failed ChromoSeq assays	As compared to failed standard of care genomic profiling assays; Each assay will be categorized as successful or failed and a two-way table constructed displaying ChromoSeq assay status by standard assay status. A Pearson chi-square test will be calculated to test the null hypothesis that assay success is independent of type of assay.	Through completion of all ChromoSeq tests (estimated to be 15 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Stakeholder perceptions of ChromoSeq	Using survey responses from treating physicians obtained from per case standardized questionnaires designed using Consolidated Framework for Implementation Research constructs; For each case, the corresponding treating physician will be asked to answer a case-based ChromoSeq Implementation Physician Survey. In order to prospectively investigate how the ChromoSeq data was used or could be used by the treating physician for each case, and to evaluate perceptions in real time, the physician will be asked to complete the survey within 1 month of the ChromoSeq and completed conventional genomic profiling results being returned to the chart, whichever is later.	Within 1 month after generation of ChromoSeq (estimated to be 2 months)
Stakeholder perceptions of ChromoSeq as measured by the Acceptability of Intervention Measure	Will complete survey at the time when 100 genomes have been sequenced; 4 statements with answers ranging from 1=completely disagree to 5=completely agree.	When 100 genomes have been sequenced (estimated to be 12 months)
Stakeholder perceptions of ChromoSeq as measured by the Intervention Appropriateness Measure	Will complete survey at the time when 100 genomes have been sequenced.; 4 statements with answers ranging from 1=completely disagree to 5=completely agree.	When 100 genomes have been sequenced (estimated to be 12 months)
Stakeholder perceptions of ChromoSeq as measured by the Feasibility of Implementation Measure	-Will complete survey at the time when 100 genomes have been sequenced. --4 statements with answers ranging from 1=completely disagree to 5=completely agree.	When 100 genomes have been sequenced (estimated to be 12 months)
Stakeholder perceptions of ChromoSeq as measured by the System Usability Scale	Will complete survey at the time when 100 genomes have been sequenced.; 10 statements about usability of ChromoSeq with answers ranging from 1=strongly disagree to 5=strongly agree	When 100 genomes have been sequenced (estimated to be 12 months)

Collaborators and Investigators

• Sponsor: Washington University School of Medicine
• Investigators: Principal Investigator: Meagan Jacoby, M.D., Ph.D., Washington University School of Medicine

Publications and helpful links

Helpful Links

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): September 17, 2021
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: July 22, 2021
• First Submitted That Met QC Criteria: July 22, 2021
• First Posted (Actual): August 3, 2021

Study Record Updates

• Last Update Posted (Estimated): October 16, 2025
• Last Update Submitted That Met QC Criteria: October 14, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Hematologic Diseases; Leukemia, Myeloid; Bone Marrow Diseases; Leukemia; Hemic and Lymphatic Diseases; Leukemia, Myeloid, Acute; Myelodysplastic Syndromes
• Other Study ID Numbers: 202105123

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Individual participant data that underlie the results reported in the article, after deidentification (text, tables, figures, and appendices).
• IPD Sharing Time Frame: Beginning 3 months and ending 5 years following article publication.
• IPD Sharing Access Criteria: Researchers who provide a methodologically sound proposal may submit proposals to mjacoby@wustl.edu. To gain access, data requestors will need to sign a data access agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ANALYTIC_CODE

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No