NCT04986657 · Washington University School of Medicine
Whole Genome Sequencing (ChromoSeq) as an Adjunct to Conventional Genomic Profiling in AML and MDS
What this study is about
This is a single institution, forward-looking 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).
View original scientific description
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).
Interventions
DEVICE
ChromoSeq
Novel, streamlined whole genome sequencing approach
Primary outcome measures
Sensitivity of ChromoSeq as measured by total number of recurrent structural variants identified
Time frame: Through completion of all ChromoSeq tests (estimated to be 15 months)
* 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
Time frame: Through completion of all ChromoSeq tests (estimated to be 15 months)
* 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
Time frame: Through completion of all ChromoSeq tests (estimated to be 15 months)
* 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
Time frame: Through completion of all ChromoSeq tests (estimated to be 15 months)
* 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
Time frame: Through completion of follow-up for all patients (estimated to be 63 months)
* 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
Time frame: Through completion of follow-up for all patients (estimated to be 63 months)
* 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
Time frame: Through completion of all ChromoSeq tests (estimated to be 15 months)
* 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
Time frame: Through completion of all ChromoSeq tests (estimated to be 15 months)
-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
Time frame: Through completion of all ChromoSeq tests (estimated to be 15 months)
* 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.
Who can participate
This study lists these criteria on ClinicalTrials.gov. A study coordinator reviews eligibility during screening — this page does not determine whether you qualify.
Inclusion criteria
- 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
- Younger than 18 years of age Exclusion Criteria Physician
- Does not treat patients at Washington University School of Medicine
Where
- St Louis, Missouri
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Frequently asked questions
What is a clinical trial?
A clinical trial is a research study that tests new medical treatments, drugs, devices, or procedures to determine their safety and effectiveness. Trials are carefully designed and monitored to protect participants while advancing medical knowledge.
Is it safe to participate?
Clinical trials follow strict safety guidelines and ethical standards. Trials must be reviewed and approved, and participants are closely monitored by medical professionals throughout the study. You can withdraw at any time if you choose.
Will I be compensated?
Many clinical trials offer compensation for your time, travel expenses, and inconvenience. The specific compensation varies by study and will be discussed during the screening process. All study-related medical care is typically provided at no cost to participants.
Will I receive a placebo instead of treatment?
When effective treatment exists, participants typically receive either the standard treatment plus the study intervention, or the standard treatment plus placebo. You would not be denied effective care. Placebos are primarily used when no proven treatment is available, or in addition to standard care. Your trial consent form will clearly explain what treatments you may receive.
Can I leave a trial if I change my mind?
Absolutely. Participation in clinical trials is completely voluntary. You have the right to withdraw from the study at any time, for any reason, without penalty or loss of benefits to which you are otherwise entitled.
How long does a clinical trial last?
Trial duration varies widely depending on the study design and purpose. Some trials last just a few weeks, while others may continue for months or years. The study coordinator will provide specific timeline information during your screening call.
Data: ClinicalTrials.gov · synced Oct 16, 2025 · Source of record for eligibility and locations