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

• ClinicalTrials.gov Identifier: NCT05434598
• Recruitment Status: Recruiting
• First Posted: June 28, 2022
• Last Update Posted: September 7, 2023
• Sponsor: Washington University School of Medicine
• Collaborator: American Society of Hematology
• Information provided by (Responsible Party): Washington University School of Medicine

Tracking Information

• First Submitted Date: June 21, 2022
• First Posted Date: June 28, 2022
• Last Update Posted Date: September 7, 2023
• Actual Study Start Date: July 27, 2022
• Estimated Primary Completion Date: July 31, 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 2, 2023)

• Rate of assay success on first attempt between ChromoSeq and conventional cytogenetics as measured by total number of recurrent structural variants identified [ Time Frame: Through completion of all ChromoSeq tests (estimated to be 24 months) ]
  -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%.
• Rate of assay success on first attempt between ChromoSeq and conventional cytogenetics as measured by total number of copy number alterations identified [ Time Frame: Through completion of all ChromoSeq tests (estimated to be 24 months) ]
  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%.
• Proportion of failed ChromoSeq assays [ Time Frame: Through completion of all ChromoSeq tests (estimated to be 24 months) ]
  • 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.

Original Primary Outcome Measures (submitted: June 21, 2022)

• Rate of assay success on first attempt between ChromoSeq and conventional cytogenetics as measured by total number of recurrent structural variants identified [ Time Frame: Through completion of all ChromoSeq tests (estimated to be 15 months) ]
  -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%.
• Rate of assay success on first attempt between ChromoSeq and conventional cytogenetics as measured by total number of copy number alterations identified [ Time Frame: Through completion of all ChromoSeq tests (estimated to be 15 months) ]
  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%.
• 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
  • 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.

Current Secondary Outcome Measures (submitted: September 2, 2023)

Stakeholder perceptions of ChromoSeq [ Time Frame: Through 1 month after generation of ChromoSeq for all patients enrolled (estimated to be 25 months) ]

• 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.

Original Secondary Outcome Measures (submitted: June 21, 2022)

Stakeholder perceptions of ChromoSeq [ Time Frame: Through 1 month after generation of ChromoSeq for all patients enrolled (estimated to be 16 months) ]

• 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.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Whole Genome Sequencing (ChromoSeq) as an Adjunct to Conventional Genomic Profiling in MDS
• Official Title: A Prospective Study of Whole Genome Sequencing (ChromoSeq) as an Adjunct to Conventional Genomic Profiling in MDS
• 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 diagnosis of myelodysplastic syndrome (MDS).
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Diagnostic

Condition

• Whole Genome Sequencing
• Myelodysplastic Syndromes

Intervention

Device: ChromoSeq

Novel, streamlined whole genome sequencing approach

Study Arms

• Experimental: Patients: ChromSeq
  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.
  Intervention: Device: ChromoSeq
• No Intervention: Stakeholders (Treating Physicians)
  Stakeholders (treating physicians) will complete surveys/questionnaires

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: June 21, 2022): 60
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: August 31, 2024
• Estimated Primary Completion Date: July 31, 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Contacts

Contact: Meagan A Jacoby, M.D., Ph.D.; 314-362-9405; mjacoby@wustl.edu

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT05434598
• Other Study ID Numbers: 202206077
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• 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

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: Individual participant data that underlie the results reported in the article, after deidentification (text, tables, figures, and appendices).
• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Supporting Materials: 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.

• Current Responsible Party: Washington University School of Medicine
• Original Responsible Party: Same as current
• Current Study Sponsor: Washington University School of Medicine
• Original Study Sponsor: Same as current
• Collaborators: American Society of Hematology

Investigators

• Principal Investigator: Meagan A Jacoby, M.D., Ph.D.; Washington University School of Medicine

• PRS Account: Washington University School of Medicine
• Verification Date: September 2023