Lymphoma, Large B-Cell, DiffuseNCT04237168
Non-invasive Tumor Immunoglobulin Gene Next Generation Sequencing (IgNGS) in Diffuse Large B Cell Lymphoma (DLBCL)
An observational study of Lymphoma, Large B-Cell, Diffuse, run by Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau at 1 site in Spain.
Trial summary
This study will evaluate IgNGS at different time points in newly diagnosed DLBCL patients homogeneously treated (RCHOP) to address its correlation with conventional techniques (i.e., positron emission tomography/computed tomography imaging (PET/CT) and outcome. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Lymphoma, Large B-Cell, Diffuse
- What is being tested?
- IgNGS from circulating tumor DNA
- How many people
- 30 participants
- Where
- 1 siteSpain
- Study dates
- Jan 2020to Jul 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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: newly DLBCL patients (diagnosed and treated in "Hospital de la Santa Creu i Sant Pau")
Who may be able to join
None listed.
Who cannot join
- Primary mediastinal DLBCL.
- Transformed DLBCL
- Patients HIV+
- Central Nervous System (CNS) DLBCL
- All other DLBCL not included under "NOS" classification, according to WHO 2016 (except those specifically indicated in "inclusion criteria").
Trial locations and contacts
1 site in 1 country.
Anna Monter-Rovira, MD contact
Spain1 site
Hospital de la Santa Creu i Sant Pau
Barcelona, 08041
Javier Briones, PhD, jbriones@santpau.cat
Anna Monter-Rovira, MD, amonter@santpau.cat
About this study
Official title: Non-invasive Tumor Immunoglobulin Gene Next Generation Sequencing (IgNGS) in Diffuse Large B Cell Lymphoma (DLBCL): Prognostic Implications and Assessment of Tumor Response
This study will evaluate IgNGS at different time points in newly diagnosed DLBCL patients homogeneously treated (RCHOP) to address its correlation with conventional techniques (i.e., positron emission tomography/computed tomography imaging (PET/CT) and outcome.
Read the detailed description
In B-cell malignancies, every lymphocyte clone expresses a unique antigen receptor structure, therefore immunoglobulin gene rearrangements (the sequence of nucleotides at the V(D)J recombination site) serves as a specific marker for each clone. Methods of analysis have changed over time to improve the sensitivity and to allow its application in clinical settings.
Diffuse Large B-cell lymphoma (DLBCL) displays molecular heterogeneity. In this context, IgNGS allows for detection of tumor clonotype from plasma (ctDNA) (Liquid Biopsy-LB) of DLBCL patients with high sensitivity and specificity. ctDNA can be tracked with this methodology in the vast majority (>90%) of patients, in contrast to NGS-methods based on genotyping for specific DLBCL mutations, which have overall low frequency. Furthermore, most newly discovered neoantigens in lymphoma derive from immunoglobulin variable sequences, supporting the relevance of the analysis of this particular region in contrast to the use of specific B-cell mutations. Importantly, preliminary studies on clonotype detection by IgNGS at the end of treatment correlate with outcome (poorer progression-free survival) and the persistence or reemergence of the tumor clonotype by ctDNA studies may anticipate the clinical relapse. We propose to evaluate IgNGS at different time points in newly diagnosed DLBCL patients treated with RCHOP to address its correlation with conventional techniques (i.e., PET/CT imaging) and outcome.
- Conditions
- Lymphoma, Large B-Cell, Diffuse
- Being tested
- IgNGS from circulating tumor DNA
- Keywords
- Diffuse large B cell lymphoma, immunoglobulin gene next generation sequencing, liquid biopsy
- Medical subject headings
- Lymphoma, Large B-Cell, Diffuse
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IgNGS from circulating tumor DNADiagnostic test
3 longitudinal plasma samples will be evaluated at three different time points per patient: 0 (pre-treatment), end of treatment, and at 6 months after treatment.
| Study group | Role | What they receive |
|---|---|---|
| DLBCL patients | newly diagnosed DLBCL (de novo, all ages) patients treated with RCHOP (first-line treatment regimen) Receives: Diagnostic Test: IgNGS from circulating tumor DNA |
What is being measured
The primary outcome is the main question the study is designed to answer.
Association between ctDNA level and clinical response at the end of treatment
Correlation between ctDNA level (in nanograms) and clinical response per PET/CT at the end of treatment (responses will be defined according to International Working Group consensus response evaluation criteria in lymphoma - IWGRECIL - 2017) will be assessed by means of Spearman correlation.
Measured: 12-18 months
Secondary outcomes (2)
Correlation between detection of tumor clonotype ctDNA and relapse
The relationship between detection of tumor clonotype ctDNA (detection: yes/no, using a frequency threshold of 5%) and relapse (disease status will be assessed by PET/CT) will be measured by means of a logistic regression model. These analyses are explorative and will be done if possible.
Measured: 18 months
Impact of IgNGS at the end of treatment and 6 months after treatment on outcome (as measured by progression-free survival PFS)
The relationship between impact of IgNGS (ctDNA level in nanograms, detection of tumor clonotype: yes/no, relative frequency of index sequences in %) with PFS will be assessed by means of a Proportional-hazards (PH) Cox regression model. These analyses are explorative and will be done if possible.
Measured: 18 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jan 2020
- Study startJan 2020 (estimated)
- Primary completionDec 2021 (estimated)
- Study completionJul 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Lymphoma, Large B-Cell, DiffuseStudies of the same condition, open and under way.
- More trials run by Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant PauThe 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
- Cohort
- Time perspective
- Prospective
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Javier Briones, Principal investigator, Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04237168
- Sponsor's protocol ID
- IIBSP-LIN-2019-83
- Status last verified
- Jan 2020
- First submitted
- 17 Jan 2020
- Last updated
- 29 Jan 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: relevant results will be published in scientific journals available to all researchers.
Publications
Herrera AF, Armand P. Minimal Residual Disease Assessment in Lymphoma: Methods and Applications. J Clin Oncol. 2017 Dec 1;35(34):3877-3887. doi: 10.1200/JCO.2017.74.5281. Epub 2017 Sep 21.
PubMed 28933999Scherer F, Kurtz DM, Newman AM, Stehr H, Craig AF, Esfahani MS, Lovejoy AF, Chabon JJ, Klass DM, Liu CL, Zhou L, Glover C, Visser BC, Poultsides GA, Advani RH, Maeda LS, Gupta NK, Levy R, Ohgami RS, Kunder CA, Diehn M, Alizadeh AA. Distinct biological subtypes and patterns of genome evolution in lymphoma revealed by circulating tumor DNA. Sci Transl Med. 2016 Nov 9;8(364):364ra155. doi: 10.1126/scitranslmed.aai8545.
PubMed 27831904Scherer F, Kurtz DM, Diehn M, Alizadeh AA. High-throughput sequencing for noninvasive disease detection in hematologic malignancies. Blood. 2017 Jul 27;130(4):440-452. doi: 10.1182/blood-2017-03-735639. Epub 2017 Jun 9.
PubMed 28600337Kurtz DM, Green MR, Bratman SV, Scherer F, Liu CL, Kunder CA, Takahashi K, Glover C, Keane C, Kihira S, Visser B, Callahan J, Kong KA, Faham M, Corbelli KS, Miklos D, Advani RH, Levy R, Hicks RJ, Hertzberg M, Ohgami RS, Gandhi MK, Diehn M, Alizadeh AA. Noninvasive monitoring of diffuse large B-cell lymphoma by immunoglobulin high-throughput sequencing. Blood. 2015 Jun 11;125(24):3679-87. doi: 10.1182/blood-2015-03-635169. Epub 2015 Apr 17.
PubMed 25887775Roschewski M, Dunleavy K, Pittaluga S, Moorhead M, Pepin F, Kong K, Shovlin M, Jaffe ES, Staudt LM, Lai C, Steinberg SM, Chen CC, Zheng J, Willis TD, Faham M, Wilson WH. Circulating tumour DNA and CT monitoring in patients with untreated diffuse large B-cell lymphoma: a correlative biomarker study. Lancet Oncol. 2015 May;16(5):541-9. doi: 10.1016/S1470-2045(15)70106-3. Epub 2015 Apr 1.
PubMed 25842160
Study at a glance
From the registry record, last updated by the sponsor on 29 Jan 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Non-invasive Tumor Immunoglobulin Gene Next Generation Sequencing (IgNGS) in Diffuse Large B Cell Lymphoma (DLBCL): Prognostic Implications and Assessment of Tumor Response
- ClinicalTrials.gov ID
- NCT04237168
- Acronym / sponsor ID
- IIBSP-LIN-2019-83
- Conditions
- Lymphoma, Large B-Cell, Diffuse
- Keywords
- Diffuse large B cell lymphoma, immunoglobulin gene next generation sequencing, liquid biopsy
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant PauUniversity, hospital or other
- Study start
- Jan 2020 (estimated)
- Primary completion
- Dec 2021 (estimated)
- Study completion
- Jul 2022 (estimated)
- First posted
- 23 Jan 2020 (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.
This study will evaluate IgNGS at different time points in newly diagnosed DLBCL patients homogeneously treated (RCHOP) to address its correlation with conventional techniques (i.e., positron emission tomography/computed tomography imaging (PET/CT) and outcome.
Detailed description
In B-cell malignancies, every lymphocyte clone expresses a unique antigen receptor structure, therefore immunoglobulin gene rearrangements (the sequence of nucleotides at the V(D)J recombination site) serves as a specific marker for each clone. Methods of analysis have changed over time to improve the sensitivity and to allow its application in clinical settings.
Diffuse Large B-cell lymphoma (DLBCL) displays molecular heterogeneity. In this context, IgNGS allows for detection of tumor clonotype from plasma (ctDNA) (Liquid Biopsy-LB) of DLBCL patients with high sensitivity and specificity. ctDNA can be tracked with this methodology in the vast majority (>90%) of patients, in contrast to NGS-methods based on genotyping for specific DLBCL mutations, which have overall low frequency. Furthermore, most newly discovered neoantigens in lymphoma derive from immunoglobulin variable sequences, supporting the relevance of the analysis of this particular region in contrast to the use of specific B-cell mutations. Importantly, preliminary studies on clonotype detection by IgNGS at the end of treatment correlate with outcome (poorer progression-free survival) and the persistence or reemergence of the tumor clonotype by ctDNA studies may anticipate the clinical relapse. We propose to evaluate IgNGS at different time points in newly diagnosed DLBCL patients treated with RCHOP to address its correlation with conventional techniques (i.e., PET/CT imaging) and outcome.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| DLBCL patients | – | Diagnostic Test: IgNGS from circulating tumor DNAnewly diagnosed DLBCL (de novo, all ages) patients treated with RCHOP (first-line treatment regimen) |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- newly DLBCL patients (diagnosed and treated in "Hospital de la Santa Creu i Sant Pau")
Key inclusion criteria (0 listed)
Key exclusion criteria (5 listed)
- Primary mediastinal DLBCL.
- Transformed DLBCL
- Patients HIV+
- Central Nervous System (CNS) DLBCL
- All other DLBCL not included under "NOS" classification, according to WHO 2016 (except those specifically indicated in "inclusion criteria").
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 |
|---|---|---|
| IgNGS from circulating tumor DNA3 longitudinal plasma samples will be evaluated at three different time points per patient: 0 (pre-treatment), end of treatment, and at 6 months after treatment. | Diagnostic test | DLBCL patients |
Primary outcome
Association between ctDNA level and clinical response at the end of treatment
Time frame: 12-18 months
Correlation between ctDNA level (in nanograms) and clinical response per PET/CT at the end of treatment (responses will be defined according to International Working Group consensus response evaluation criteria in lymphoma - IWGRECIL - 2017) will be assessed by means of Spearman correlation.
2 secondary outcomes
Correlation between detection of tumor clonotype ctDNA and relapse
Time frame: 18 months
Impact of IgNGS at the end of treatment and 6 months after treatment on outcome (as measured by progression-free survival PFS)
Time frame: 18 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Jan 2020.
- Background: PubMed 28933999Herrera AF, Armand P. Minimal Residual Disease Assessment in Lymphoma: Methods and Applications. J Clin Oncol. 2017 Dec 1;35(34):3877-3887. doi: 10.1200/JCO.2017.74.5281. Epub 2017 Sep 21.
- Background: PubMed 27831904Scherer F, Kurtz DM, Newman AM, Stehr H, Craig AF, Esfahani MS, Lovejoy AF, Chabon JJ, Klass DM, Liu CL, Zhou L, Glover C, Visser BC, Poultsides GA, Advani RH, Maeda LS, Gupta NK, Levy R, Ohgami RS, Kunder CA, Diehn M, Alizadeh AA. Distinct biological subtypes and patterns of genome evolution in lymphoma revealed by circulating tumor DNA. Sci Transl Med. 2016 Nov 9;8(364):364ra155. doi: 10.1126/scitranslmed.aai8545.
- Background: PubMed 28600337Scherer F, Kurtz DM, Diehn M, Alizadeh AA. High-throughput sequencing for noninvasive disease detection in hematologic malignancies. Blood. 2017 Jul 27;130(4):440-452. doi: 10.1182/blood-2017-03-735639. Epub 2017 Jun 9.
- Background: PubMed 25887775Kurtz DM, Green MR, Bratman SV, Scherer F, Liu CL, Kunder CA, Takahashi K, Glover C, Keane C, Kihira S, Visser B, Callahan J, Kong KA, Faham M, Corbelli KS, Miklos D, Advani RH, Levy R, Hicks RJ, Hertzberg M, Ohgami RS, Gandhi MK, Diehn M, Alizadeh AA. Noninvasive monitoring of diffuse large B-cell lymphoma by immunoglobulin high-throughput sequencing. Blood. 2015 Jun 11;125(24):3679-87. doi: 10.1182/blood-2015-03-635169. Epub 2015 Apr 17.
- Background: PubMed 25842160Roschewski M, Dunleavy K, Pittaluga S, Moorhead M, Pepin F, Kong K, Shovlin M, Jaffe ES, Staudt LM, Lai C, Steinberg SM, Chen CC, Zheng J, Willis TD, Faham M, Wilson WH. Circulating tumour DNA and CT monitoring in patients with untreated diffuse large B-cell lymphoma: a correlative biomarker study. Lancet Oncol. 2015 May;16(5):541-9. doi: 10.1016/S1470-2045(15)70106-3. Epub 2015 Apr 1.
- Individual participant dataSharing planned: No. relevant results will be published in scientific journals available to all researchers.
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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.
Anna Monter-Rovira, MD contact
Javier Briones principal investigator
Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau
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 Lymphoma, Large B-Cell, Diffuse, run by Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau at 1 site in Spain.
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 0 inclusion and 5 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 29 Jan 2020. 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 Spain. 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 Javier Briones, PhD (+34935565649, jbriones@santpau.cat), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Association between ctDNA level and clinical response at the end of treatment (time frame: 12-18 months). 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 NCT04237168, which also lists 5 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 29 Jan 2020.