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

Study Overview
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Brief Summary
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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 diagnosis of myelodysplastic syndrome (MDS).

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

Conditions
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Whole Genome Sequencing, Myelodysplastic Syndromes

Intervention / Treatment
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* Device: ChromoSeq


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Patient: Diagnosis of MDS, or a clinical suspicion for a new diagnosis of MDS, for whom routine diagnostic testing is requested or planned to be requested. Seen in the outpatient setting. Not been previously treated with disease-modifying therapy (such as lenalidomide or hypomethylating agents). Note: Patients who have received transfusional support, erythropoietin-stimulating agents, growth factor support, or luspatercept are eligible. At least 18 years of age. -Able to understand and willing 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 stakeholder perceptions of ChromoSeq during the ChromoSeq implementation process. (Written documentation of informed consent is not required.) Exclusion Criteria Patient: -Younger than 18 years of age Exclusion Criteria Physician -Does not treat patients at Washington University School of Medicine

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Patients: ChromSeq<br>ChromoSeq will be performed on bone marrow or peripheral blood 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<br>* Novel, streamlined whole genome sequencing approach<br>|
| No Intervention: Stakeholders (Treating Physicians)<br>Stakeholders (treating physicians) will complete surveys/questionnaires | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of assay success on first attempt between ChromoSeq and conventional cytogenetics as measured by total number of recurrent structural variants identified | -The number of recurrent structural variants detected by ChromoSeq will be compared to those detected by conventional cytogenetics using two non-inferiority tests for dependent samples using non-inferiority margin of 1%. | Through completion of all ChromoSeq tests (estimated to be 24 months) | 
| Rate of assay success on first attempt between ChromoSeq and conventional cytogenetics as measured by total number of copy number alterations identified | The number of copy number alterations detected by ChromoSeq will be compared to those detected by conventional cytogenetics using two non-inferiority tests for dependent samples using non-inferiority margin of 1%. | Through completion of all ChromoSeq tests (estimated to be 24 months) | 
| Proportion of failed ChromoSeq assays | As compared to failed standard of care genomic profiling assays The proportion of first-run failures for ChromoSeq assays will be compared to the proportion of failed standard of care genomic profiling assays using a directional Fisher's exact test. | Through completion of all ChromoSeq tests (estimated to be 24 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. | Through 1 month after generation of ChromoSeq for all patients enrolled (estimated to be 25 months) |