Multiple MyelomaEUCADDNCT04122092
Evaluation of Ultrasensitive Chromosomal Aneuploidy Detection for Detecting Minimal Residual Disease in Multiple Myeloma
An observational study of Multiple Myeloma, run by Shanghai Changzheng Hospital at 1 site in China.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Multiple Myeloma
- What is being tested?
- The level of plasma cfDNA CINs
- How many people
- 100 participants
- Where
- 1 siteChina
- Study dates
- 20 Oct 2019to 20 Oct 2022
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
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.
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Juan Du
Shanghai
Juan Du, PhD, 8615800706091 ext. 8615800706091, changzheng_pg@163.com
Ziliang Qian, PhD, ziliang.qian@prophetgenomics.com.cn
About this study
Official title: Application of Ultrasensitive Chromosomal Aneuploidy Detection (UCAD) as a Surrogate Biomarker of Minimal Residual Diseases for Multiple Myeloma Patients
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.
Read the 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.
- Conditions
- Multiple Myeloma
- Being tested
- The level of plasma cfDNA CINs
- Keywords
- Multiple myeloma, Minimal residual disease, Chromosomal aneuploidy detection, Chromosomal instability
- Medical subject headings
- Multiple Myeloma, Neoplasm, Residual, Chromosomal Instability
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
The level of plasma cfDNA CINsDiagnostic test
The extracted cfDNA from PB will be analyzed by UCAD to determine the level of CINs
| Study group | Role | What they receive |
|---|---|---|
| MM patients have curative effect at least VGPR | We will detect cfDNA CIN of multiple myeloma patients who have the curative effect at least very good partial response (VGPR) after front line therapy, and then monitoring cfDNA CIN every two treatment cycles or every three months during follow up，the result will be compared with bone marrow aspiration MFC. Receives: Diagnostic Test: The level of plasma cfDNA CINs |
What is being measured
The primary outcome is the main question the study is designed to answer.
Comparison of the prognostic of the MRD negative and MRD positive defined by UCAD
The patients' prognostic was evaluated with the median time of progress free survival (PFS) and overall survival (OS)
Measured: 36month
The concordance rate analysis between UCAD and multiparameter flow cytometry(MFC)
number of patients "declared MRD positive or MRD negative" with the UCAD and MFC test simultaneously among the patients being tested successfully with both
Measured: 36month
Secondary outcomes (2)
The applicability analysis of UCAD
number of patients being tested successfully with the UCAD among the patients included in this cohort
Measured: 36month
The MRD negative rate analysis among VGPR patients
The MRD negative patients accounted for the total enrollment
Measured: 24month
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Oct 2019
- Study start20 Oct 2019
- Primary completion20 Oct 2021 (estimated)
- Study completion20 Oct 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (8)Papers the sponsor has linked to this study.
- Other trials for Multiple MyelomaStudies of the same condition, open and under way.
- More trials run by Shanghai Changzheng HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Shanghai Changzheng Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Juan Du, Shanghai Changzheng Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04122092
- Sponsor's protocol ID
- cz-pg001
- Acronym
- EUCADD
- Status last verified
- Nov 2019
- First submitted
- 8 Oct 2019
- Last updated
- 18 Nov 2019
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Bakhoum SF, Ngo B, Laughney AM, Cavallo JA, Murphy CJ, Ly P, Shah P, Sriram RK, Watkins TBK, Taunk NK, Duran M, Pauli C, Shaw C, Chadalavada K, Rajasekhar VK, Genovese G, Venkatesan S, Birkbak NJ, McGranahan N, Lundquist M, LaPlant Q, Healey JH, Elemento O, Chung CH, Lee NY, Imielenski M, Nanjangud G, Pe'er D, Cleveland DW, Powell SN, Lammerding J, Swanton C, Cantley LC. Chromosomal instability drives metastasis through a cytosolic DNA response. Nature. 2018 Jan 25;553(7689):467-472. doi: 10.1038/nature25432. Epub 2018 Jan 17.
PubMed 29342134Hieronymus H, Murali R, Tin A, Yadav K, Abida W, Moller H, Berney D, Scher H, Carver B, Scardino P, Schultz N, Taylor B, Vickers A, Cuzick J, Sawyers CL. Tumor copy number alteration burden is a pan-cancer prognostic factor associated with recurrence and death. Elife. 2018 Sep 4;7:e37294. doi: 10.7554/eLife.37294.
PubMed 30178746Bai Y, Orfao A, Chim CS. Molecular detection of minimal residual disease in multiple myeloma. Br J Haematol. 2018 Apr;181(1):11-26. doi: 10.1111/bjh.15075. Epub 2017 Dec 19.
PubMed 29265356Martinez-Lopez J, Lahuerta JJ, Pepin F, Gonzalez M, Barrio S, Ayala R, Puig N, Montalban MA, Paiva B, Weng L, Jimenez C, Sopena M, Moorhead M, Cedena T, Rapado I, Mateos MV, Rosinol L, Oriol A, Blanchard MJ, Martinez R, Blade J, San Miguel J, Faham M, Garcia-Sanz R. Prognostic value of deep sequencing method for minimal residual disease detection in multiple myeloma. Blood. 2014 May 15;123(20):3073-9. doi: 10.1182/blood-2014-01-550020. Epub 2014 Mar 19.
PubMed 24646471Oberle A, Brandt A, Voigtlaender M, Thiele B, Radloff J, Schulenkorf A, Alawi M, Akyuz N, Marz M, Ford CT, Krohn-Grimberghe A, Binder M. Monitoring multiple myeloma by next-generation sequencing of V(D)J rearrangements from circulating myeloma cells and cell-free myeloma DNA. Haematologica. 2017 Jun;102(6):1105-1111. doi: 10.3324/haematol.2016.161414. Epub 2017 Feb 9.
PubMed 28183851Rihova L, Vsianska P, Bezdekova R, Kralova R, Penka M, Krejci M, Pour L, Hajek R. Minimal Residual Disease Assessment in Multiple Myeloma by Multiparametric Flow Cytometry. Klin Onkol. 2017 Summer;30(Supplementum2):21-28. doi: 10.14735/amko20172S21.
PubMed 28903567Berger N, Kim-Schulze S, Parekh S. Minimal Residual Disease in Multiple Myeloma: Impact on Response Assessment, Prognosis and Tumor Heterogeneity. Adv Exp Med Biol. 2018;1100:141-159. doi: 10.1007/978-3-319-97746-1_9.
PubMed 30411265Li H, Li F, Zhou X, Mei J, Song P, An Z, Zhao Q, Guo X, Wang X, Zhai Y. Achieving minimal residual disease-negative by multiparameter flow cytometry may ameliorate a poor prognosis in MM patients with high-risk cytogenetics: a retrospective single-center analysis. Ann Hematol. 2019 May;98(5):1185-1195. doi: 10.1007/s00277-019-03609-x. Epub 2019 Feb 5.
PubMed 30721336
Study at a glance
From the registry record, last updated by the sponsor on 18 Nov 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Application of Ultrasensitive Chromosomal Aneuploidy Detection (UCAD) as a Surrogate Biomarker of Minimal Residual Diseases for Multiple Myeloma Patients
- ClinicalTrials.gov ID
- NCT04122092
- Acronym / sponsor ID
- EUCADD / cz-pg001
- Conditions
- Multiple Myeloma
- Keywords
- Multiple myeloma, Minimal residual disease, Chromosomal aneuploidy detection, Chromosomal instability
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- Shanghai Changzheng HospitalUniversity, hospital or other
- Study start
- 20 Oct 2019 (actual)
- Primary completion
- 20 Oct 2021 (estimated)
- Study completion
- 20 Oct 2022 (estimated)
- First posted
- 10 Oct 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| MM patients have curative effect at least VGPR | – | Diagnostic Test: The level of plasma cfDNA CINsWe will detect cfDNA CIN of multiple myeloma patients who have the curative effect at least very good partial response (VGPR) after front line therapy, and then monitoring cfDNA CIN every two treatment cycles or every three months during follow up，the result will be compared with bone marrow aspiration MFC. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- 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.
Key inclusion criteria (3 listed)
- 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.
Key exclusion criteria (3 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| The level of plasma cfDNA CINsThe extracted cfDNA from PB will be analyzed by UCAD to determine the level of CINs | Diagnostic test | MM patients have curative effect at least VGPR |
Primary outcome
Comparison of the prognostic of the MRD negative and MRD positive defined by UCAD
Time frame: 36month
The patients' prognostic was evaluated with the median time of progress free survival (PFS) and overall survival (OS)
The concordance rate analysis between UCAD and multiparameter flow cytometry(MFC)
Time frame: 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
2 secondary outcomes
The applicability analysis of UCAD
Time frame: 36month
The MRD negative rate analysis among VGPR patients
Time frame: 24month
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Nov 2019.
- Background: PubMed 29342134Bakhoum SF, Ngo B, Laughney AM, Cavallo JA, Murphy CJ, Ly P, Shah P, Sriram RK, Watkins TBK, Taunk NK, Duran M, Pauli C, Shaw C, Chadalavada K, Rajasekhar VK, Genovese G, Venkatesan S, Birkbak NJ, McGranahan N, Lundquist M, LaPlant Q, Healey JH, Elemento O, Chung CH, Lee NY, Imielenski M, Nanjangud G, Pe'er D, Cleveland DW, Powell SN, Lammerding J, Swanton C, Cantley LC. Chromosomal instability drives metastasis through a cytosolic DNA response. Nature. 2018 Jan 25;553(7689):467-472. doi: 10.1038/nature25432. Epub 2018 Jan 17.
- Background: PubMed 30178746Hieronymus H, Murali R, Tin A, Yadav K, Abida W, Moller H, Berney D, Scher H, Carver B, Scardino P, Schultz N, Taylor B, Vickers A, Cuzick J, Sawyers CL. Tumor copy number alteration burden is a pan-cancer prognostic factor associated with recurrence and death. Elife. 2018 Sep 4;7:e37294. doi: 10.7554/eLife.37294.
- Background: PubMed 29265356Bai Y, Orfao A, Chim CS. Molecular detection of minimal residual disease in multiple myeloma. Br J Haematol. 2018 Apr;181(1):11-26. doi: 10.1111/bjh.15075. Epub 2017 Dec 19.
- Background: PubMed 24646471Martinez-Lopez J, Lahuerta JJ, Pepin F, Gonzalez M, Barrio S, Ayala R, Puig N, Montalban MA, Paiva B, Weng L, Jimenez C, Sopena M, Moorhead M, Cedena T, Rapado I, Mateos MV, Rosinol L, Oriol A, Blanchard MJ, Martinez R, Blade J, San Miguel J, Faham M, Garcia-Sanz R. Prognostic value of deep sequencing method for minimal residual disease detection in multiple myeloma. Blood. 2014 May 15;123(20):3073-9. doi: 10.1182/blood-2014-01-550020. Epub 2014 Mar 19.
- Background: PubMed 28183851Oberle A, Brandt A, Voigtlaender M, Thiele B, Radloff J, Schulenkorf A, Alawi M, Akyuz N, Marz M, Ford CT, Krohn-Grimberghe A, Binder M. Monitoring multiple myeloma by next-generation sequencing of V(D)J rearrangements from circulating myeloma cells and cell-free myeloma DNA. Haematologica. 2017 Jun;102(6):1105-1111. doi: 10.3324/haematol.2016.161414. Epub 2017 Feb 9.
- Background: PubMed 28903567Rihova L, Vsianska P, Bezdekova R, Kralova R, Penka M, Krejci M, Pour L, Hajek R. Minimal Residual Disease Assessment in Multiple Myeloma by Multiparametric Flow Cytometry. Klin Onkol. 2017 Summer;30(Supplementum2):21-28. doi: 10.14735/amko20172S21.
- Background: PubMed 30411265Berger N, Kim-Schulze S, Parekh S. Minimal Residual Disease in Multiple Myeloma: Impact on Response Assessment, Prognosis and Tumor Heterogeneity. Adv Exp Med Biol. 2018;1100:141-159. doi: 10.1007/978-3-319-97746-1_9.
- Background: PubMed 30721336Li H, Li F, Zhou X, Mei J, Song P, An Z, Zhao Q, Guo X, Wang X, Zhai Y. Achieving minimal residual disease-negative by multiparameter flow cytometry may ameliorate a poor prognosis in MM patients with high-risk cytogenetics: a retrospective single-center analysis. Ann Hematol. 2019 May;98(5):1185-1195. doi: 10.1007/s00277-019-03609-x. Epub 2019 Feb 5.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Multiple Myeloma, run by Shanghai Changzheng Hospital at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 18 Nov 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Juan Du, PhD (8615800706091 ext. 8615800706091, changzheng_pg@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Comparison of the prognostic of the MRD negative and MRD positive defined by UCAD (time frame: 36month). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04122092, which also lists 8 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Nov 2019.