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

NCT04986657 | Recruiting FDA Device

• 1 other identifier: 202105123
• Study Type: interventional
• Target: 325
• Locations: 1 country
• Sites: 1

Brief Summary

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).

Conditions

Whole Genome Sequencing; Acute Myeloid Leukemia; Myelodysplastic Syndromes

Outcome Measures

Primary Outcomes (9)

• 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 Outcomes (5)

• Stakeholder perceptions of ChromoSeq

  Within 1 month after generation of ChromoSeq (estimated to be 2 months)

• Stakeholder perceptions of ChromoSeq as measured by the Acceptability of Intervention Measure

  When 100 genomes have been sequenced (estimated to be 12 months)

• Stakeholder perceptions of ChromoSeq as measured by the Intervention Appropriateness Measure

  When 100 genomes have been sequenced (estimated to be 12 months)

• Stakeholder perceptions of ChromoSeq as measured by the Feasibility of Implementation Measure

  When 100 genomes have been sequenced (estimated to be 12 months)

• Stakeholder perceptions of ChromoSeq as measured by the System Usability Scale

  When 100 genomes have been sequenced (estimated to be 12 months)

Study Arms (2)

Patients: ChromoSeq

EXPERIMENTAL

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

Stakeholders (Treating Physicians)

NO 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.

Interventions

ChromoSeq DEVICE

Novel, streamlined whole genome sequencing approach

Patients: ChromoSeq

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• Younger than 18 years of age
• Does not treat patients at Washington University School of Medicine

Sponsors & Collaborators

• Washington University School of Medicine: lead

Study Sites (1)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

RECRUITING

Related Links

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

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Myelodysplastic Syndromes

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Diseases

Study Officials

• Meagan Jacoby, M.D., Ph.D.

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Central Study Contacts

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

CONTACT

314-747-8439; mjacoby@wustl.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 22, 2021
• First Posted: August 3, 2021
• Study Start: September 17, 2021
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: October 16, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ANALYTIC CODE
• Time Frame: Beginning 3 months and ending 5 years following article publication.
• 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.

Locations

US (1)