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

Acute Myeloid Leukemia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04986657
• Other study ID #: 202105123
• Status: Recruiting
• Phase: N/A
• Start date: September 17, 2021
• Est. completion date: December 31, 2027

Study information

• Verified date: December 2023
• Source: Washington University School of Medicine
• Contact: Meagan Jacoby, M.D., Ph.D.
• Phone: 314-747-8439
• Email: mjacoby[@]wustl.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 225
• Est. completion date: December 31, 2027
• Est. primary completion date: December 31, 2027
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Acute Myeloid Leukemia
• Myelodysplastic Syndromes
• Whole Genome Sequencing

Intervention

Device:
• ChromoSeq
Novel, streamlined whole genome sequencing approach

Locations

Country	Name	City	State
United States	Washington University School of Medicine	Saint Louis	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
Washington University School of Medicine

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)

External Links

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