Back to resultsWhole Genome Sequencing (ChromoSeq) as an Adjunct to Conventional Genomic Profiling in AML and MDS
Primary Purpose
Whole Genome Sequencing, Acute Myeloid Leukemia, Myelodysplastic Syndromes
Status
Recruiting
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
ChromoSeq
Sponsored by
About this trial
This is an interventional diagnostic trial for Whole Genome Sequencing
Eligibility Criteria
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
Sites / Locations
- Washington University School of MedicineRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
No Intervention
Arm Label
Patients: ChromoSeq
Stakeholders (Treating Physicians)
Arm Description
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.
-Stakeholders (treating physicians) will complete surveys/questionnaires
Outcomes
Primary Outcome Measures
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.
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.
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.
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.
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.
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.
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.
ChromoSeq turnaround time
-Measured from time of order requisition (hematologic molecular algorithm from Barnes Jewish Hospital) to return of report to the medical record
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.
Secondary Outcome Measures
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.
Stakeholder perceptions of ChromoSeq as measured by the Acceptability of Intervention Measure
Will complete survey at the time when 100 genomes have been sequenced and at the time when 200 genomes have been sequenced.
4 statements with answers ranging from 1=completely disagree to 5=completely agree.
Stakeholder perceptions of ChromoSeq as measured by the Intervention Appropriateness Measure
Will complete survey at the time when 100 genomes have been sequenced and at the time when 200 genomes have been sequenced.
4 statements with answers ranging from 1=completely disagree to 5=completely agree.
Stakeholder perceptions of ChromoSeq as measured by the Feasibility of Implementation Measure
-Will complete survey at the time when 100 genomes have been sequenced and at the time when 200 genomes have been sequenced.
--4 statements with answers ranging from 1=completely disagree to 5=completely agree.
Stakeholder perceptions of ChromoSeq as measured by the System Usability Scale
Will complete survey at the time when 100 genomes have been sequenced and at the time when 200 genomes have been sequenced.
10 statements about usability of ChromoSeq with answers ranging from 1=strongly disagree to 5=strongly agree
Full Information
NCT ID
NCT04986657
First Posted
July 22, 2021
Last Updated
April 11, 2023
Sponsor
Washington University School of Medicine
1. Study Identification
Unique Protocol Identification Number
NCT04986657
Brief Title
Whole Genome Sequencing (ChromoSeq) as an Adjunct to Conventional Genomic Profiling in AML and MDS
Official Title
A Prospective Study of Whole Genome Sequencing (ChromoSeq) as an Adjunct to Conventional Genomic Profiling in AML and MDS
Study Type
Interventional
2. Study Status
Record Verification Date
April 2023
Overall Recruitment Status
Recruiting
Study Start Date
September 17, 2021 (Actual)
Primary Completion Date
December 31, 2027 (Anticipated)
Study Completion Date
December 31, 2027 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Washington University School of Medicine
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
Yes
Device Product Not Approved or Cleared by U.S. FDA
Yes
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No
5. Study Description
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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Whole Genome Sequencing, Acute Myeloid Leukemia, Myelodysplastic Syndromes
7. Study Design
Primary Purpose
Diagnostic
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
225 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Patients: ChromoSeq
Arm Type
Experimental
Arm Description
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.
Arm Title
Stakeholders (Treating Physicians)
Arm Type
No Intervention
Arm Description
-Stakeholders (treating physicians) will complete surveys/questionnaires
Intervention Type
Device
Intervention Name(s)
ChromoSeq
Intervention Description
Novel, streamlined whole genome sequencing approach
Primary Outcome Measure Information:
Title
Sensitivity of ChromoSeq as measured by total number of recurrent structural variants identified
Description
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.
Time Frame
Through completion of all ChromoSeq tests (estimated to be 15 months)
Title
Sensitivity of ChromoSeq as measured by total number of copy number alterations identified
Description
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.
Time Frame
Through completion of all ChromoSeq tests (estimated to be 15 months)
Title
Sensitivity of ChromoSeq as measured by number of single nucleotide variants identified
Description
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.
Time Frame
Through completion of all ChromoSeq tests (estimated to be 15 months)
Title
Sensitivity of ChromoSeq as measured by number of insertion-deletions identified
Description
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.
Time Frame
Through completion of all ChromoSeq tests (estimated to be 15 months)
Title
Determine if risk-stratification using ChromoSeq correlates with overall-survival
Description
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.
Time Frame
Through completion of follow-up for all patients (estimated to be 63 months)
Title
Determine if risk-stratification using ChromoSeq correlates with event-free survival
Description
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.
Time Frame
Through completion of follow-up for all patients (estimated to be 63 months)
Title
Proportion of cases in which ChromoSeq provides new genetic information to the clinician
Description
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.
Time Frame
Through completion of all ChromoSeq tests (estimated to be 15 months)
Title
ChromoSeq turnaround time
Description
-Measured from time of order requisition (hematologic molecular algorithm from Barnes Jewish Hospital) to return of report to the medical record
Time Frame
Through completion of all ChromoSeq tests (estimated to be 15 months)
Title
Proportion of failed ChromoSeq assays
Description
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.
Time Frame
Through completion of all ChromoSeq tests (estimated to be 15 months)
Secondary Outcome Measure Information:
Title
Stakeholder perceptions of ChromoSeq
Description
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.
Time Frame
Through 1 month after generation of ChromoSeq for all patients enrolled (estimated to be 16 months)
Title
Stakeholder perceptions of ChromoSeq as measured by the Acceptability of Intervention Measure
Description
Will complete survey at the time when 100 genomes have been sequenced and at the time when 200 genomes have been sequenced.
4 statements with answers ranging from 1=completely disagree to 5=completely agree.
Time Frame
Through conclusion of study (when 200 genomes have been sequenced - estimated to be 15 months)
Title
Stakeholder perceptions of ChromoSeq as measured by the Intervention Appropriateness Measure
Description
Will complete survey at the time when 100 genomes have been sequenced and at the time when 200 genomes have been sequenced.
4 statements with answers ranging from 1=completely disagree to 5=completely agree.
Time Frame
Through conclusion of study (when 200 genomes have been sequenced - estimated to be 15 months)
Title
Stakeholder perceptions of ChromoSeq as measured by the Feasibility of Implementation Measure
Description
-Will complete survey at the time when 100 genomes have been sequenced and at the time when 200 genomes have been sequenced.
--4 statements with answers ranging from 1=completely disagree to 5=completely agree.
Time Frame
Through conclusion of study (when 200 genomes have been sequenced - estimated to be 15 months)
Title
Stakeholder perceptions of ChromoSeq as measured by the System Usability Scale
Description
Will complete survey at the time when 100 genomes have been sequenced and at the time when 200 genomes have been sequenced.
10 statements about usability of ChromoSeq with answers ranging from 1=strongly disagree to 5=strongly agree
Time Frame
Through conclusion of study (when 200 genomes have been sequenced - estimated to be 15 months)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Meagan Jacoby, M.D., Ph.D.
Phone
314-747-8439
Email
mjacoby@wustl.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Meagan Jacoby, M.D., Ph.D.
Organizational Affiliation
Washington University School of Medicine
Official's Role
Principal Investigator
Facility Information:
Facility Name
Washington University School of Medicine
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Meagan Jacoby, M.D., Ph.D.
Phone
314-747-8439
Email
mjacoby@wustl.edu
First Name & Middle Initial & Last Name & Degree
Meagan Jacoby, M.D., Ph.D.
First Name & Middle Initial & Last Name & Degree
Timothy Ley, M.D.
First Name & Middle Initial & Last Name & Degree
Mary Politi, Ph.D.
First Name & Middle Initial & Last Name & Degree
David Spencer, M.D., Ph.D.
First Name & Middle Initial & Last Name & Degree
Jack Baty
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing 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.
Links:
URL
http://www.siteman.wustl.edu
Description
Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine
Learn more about this trial
Whole Genome Sequencing (ChromoSeq) as an Adjunct to Conventional Genomic Profiling in AML and MDS
We'll reach out to this number within 24 hrs