Clinical trial NCT04122092: Evaluation of Ultrasensitive Chromosomal Aneuploidy Detection for Detecting Minimal Residual Disease in Multiple Myeloma
Official title: Application of Ultrasensitive Chromosomal Aneuploidy Detection (UCAD) as a Surrogate Biomarker of Minimal Residual Diseases for Multiple Myeloma Patients
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Multiple Myeloma
Keywords: Multiple myeloma
Minimal residual disease
Chromosomal aneuploidy detection
Chromosomal instability
Lead sponsor: Shanghai Changzheng Hospital
Sponsor class: OTHER
First posted: 2019-10-10
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients diagnosed with MM and with the curative effect at least VGPR in Changzheng Hospital from Aug 2019 till the end of this study.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Comparison of the prognostic of the MRD negative and MRD positive defined by UCAD
timeFrame: 36month
measure: The concordance rate analysis between UCAD and multiparameter flow cytometry(MFC)
timeFrame: 36month
Secondary outcomes:
measure: The applicability analysis of UCAD
timeFrame: 36month
measure: The MRD negative rate analysis among VGPR patients
timeFrame: 24month
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Juan Du
Study officials:
References:
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