Evaluation of Ultrasensitive Chromosomal Aneuploidy Detection for Detecting Minimal Residual Disease in Multiple Myeloma

• Conditions: Multiple Myeloma

• Registration Number: NCT04122092
• Lead Sponsor: Shanghai Changzheng Hospital

Brief Summary

Despite the significantly higher complete remission rates and improved survival achieved over the last decade，multiple myeloma (MM) patients continue to relapse due to persistence of minimal residual disease (MRD). Currently, numerous studies have evaluated the prognostic value of MRD by detecting immunophenotypic and immunoglobulin (Ig) gene rearrangements from bone marrow aspiration samples. Here the investigators intend to study the clinical utility of Ultrasensitive Chromosomal Aneuploidy Detection (UCAD) as an MRD assay, which is based on plasma cell-free DNA(cfDNA) low-coverage whole-genome sequencing. UCAD is non-invasive and applicable for tumors with high heterogeneity and extramedullary invasions.

Detailed Description

In multiple myeloma, Minimal Residual Disease (MRD) refers to myeloma cells that are present in the bone marrow after a clinical response has been measured and the patient is in remission. A patient who tests "MRD negative" after treatment for myeloma has less than one myeloma cell per million bone marrow cells. Data from recent clinical trials suggest that patients with such a low level of disease may be less likely to experience a relapse of their condition than patients with higher levels. In recent years, MRD testing is now be applied in the management of patients receiving standard therapies for the disease.

Chromosomal instability(CIN) results from errors in chromosome segregation during mitosis, leading to structural and numerical chromosomal abnormalities. It will generate genomic heterogeneity that acts as a substrate for natural selection. Furthermore, it is proved that tumors with aneuploidies and polyploidy resulting from whole-genome doubling are related with metastasis, treatment resistance, and decreased overall survival. It is estimated that 60%-80% of human tumors exhibit chromosomal abnormalities suggestive of CIN. CIN positively correlates with tumor stage and is enriched in relapsed as well as metastatic tumor specimens. Due to the ubiquity of CIN in cancer cells and cancer cell releasing DNA into peripheral blood (PB) when apoptosis, it is a potentially non-invasive way to detect CIN in PB cfDNA from the MM patients to character MRD level. UCAD is a new method to detecting CIN in the DNA sample from patients, including extracting cfDNA from PB, analyzing DNA by low-coverage whole-genome sequencing, processing the data by bio-information techniques, and finally optimizing the management of MM patients.

Study Timeline

• Study First Submitted: 2019-10-08
• Study First Submitted QC: 2019-10-08
• Study First Posted: 2019-10-10
• Study Start: 2019-10-20
• Status Verified: 2019-11
• Last Update Submitted: 2019-11-15
• Last Update Posted: 2019-11-18
• Primary Completion: 2021-10-20
• Study Completion: 2022-10-20

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 100

Inclusion Criteria

• Patients new diagnosed with MM and with the curative effect at least VGPR.
• Male or female patients aged >= 18 years.
• Participants signed informed consent form.

Exclusion Criteria

• Age under 18 years
• Individuals unwilling to sign the consent form or unwilling to provide PB for test or unwilling to provide the medical record.
• Individuals unwilling to participate in this trial.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
The concordance rate analysis between UCAD and multiparameter flow cytometry(MFC)	36month	number of patients "declared MRD positive or MRD negative" with the UCAD and MFC test simultaneously among the patients being tested successfully with both
Comparison of the prognostic of the MRD negative and MRD positive defined by UCAD	36month	The patients' prognostic was evaluated with the median time of progress free survival (PFS) and overall survival (OS)

Secondary Outcome Measures

Name	Time	Method
The applicability analysis of UCAD	36month	number of patients being tested successfully with the UCAD among the patients included in this cohort
The MRD negative rate analysis among VGPR patients	24month	The MRD negative patients accounted for the total enrollment

Trial Locations

Locations (1)

Juan Du; 🇨🇳 Shanghai, China