Lymphoma, B-cell, Aggressive Non-Hodgkin (B-NHL)ExoReBLyNCT03985696
Exosomes and Immunotherapy in Non-Hodgkin B-cell Lymphomas
A study testing blood sample in people with Lymphoma, B-cell, Aggressive Non-Hodgkin (B-NHL), run by University Hospital, Limoges at 1 site in France.
Trial summary
Diffuse large B-cell lymphomas (DLBCL) are highly aggressive and heterogeneous B-cell lymphoma that would imminently be fatal without treatment. Monoclonal anti-CD20 antibody, rituximab, in combination of CHOP chemotherapy (R-CHOP) is widely used with favourable results. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Lymphoma, B-cell, Aggressive Non-Hodgkin (B-NHL)
- What is being tested?
- blood sample
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 90 participants
- Where
- 1 siteFrance
- Study dates
- 2 Jul 2019to 2 Jul 2025
- Phase
- Interventional
- 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
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- patients over 18 years old with DLBCL at diagnostic or relapsed patients after R-CHOP therapy.
- Healthy volunteers over 18 years old
Who cannot join
- other B cell diseases
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Exosomes and Resistance to Immunotherapy in Aggressive Non-Hodgkin B-cell Lymphomas (B-NHL)
Diffuse large B-cell lymphomas (DLBCL) are highly aggressive and heterogeneous B-cell lymphoma that would imminently be fatal without treatment. Monoclonal anti-CD20 antibody, rituximab, in combination of CHOP chemotherapy (R-CHOP) is widely used with favourable results. Although more than half of patients achieve long-term remission, many are not cured with this immunotherapy. Suboptimal response and/or resistance to rituximab have remained a challenge in the therapy of DLBCL but also of all B-NHL. Exosomes are microvesicles released from tumor B cells that are found in plasma of patients with B-NHL. Exosomes carry therapeutic targets (as CD20, PDL-1) and could act as "decoy-receptors" for immunotherapy. Our objective is to precise, in aggressive B-NHL, the role of exosomes in immunotherapy escape.
Read the detailed description
Diffuse large B-cell lymphomas (DLBCL) are highly aggressive and heterogeneous B-cell lymphoma that would imminently be fatal without treatment. Monoclonal anti-CD20 antibody, rituximab, in combination of CHOP chemotherapy (R-CHOP) is widely used with favourable results. Although more than half of patients achieve long-term remission, many are not cured with this immunotherapy. Decreased CD20 expression has been postulated to be one of the most important contributing to rituximab resistance. Moreover, R-CHOP therapies are sometimes ineffective, and new treatment strategies based notably on host immune responses modulation are being explored. Among them, programmed cell death ligand 1 (PD-L1) protein was identified as a potent predicting biomarker in DLBCL. Exosomes are small membrane vesicles secreted by several cell types during exocytic fusion of multivesicular bodies with the plasma membrane. Many cancer cells have been shown to secrete exosomes in greater amounts than normal cells. Exosome secretion may contribute to drug resistance. Indeed, exosome release from B-cell Non-Hodgkin Lymphoma (B-NHL), by the expression of CD20, has been suggest to act as decoy targets upon rituximab exposure, allowing lymphoma cells to escape from humoral immunotherapy. Finally, as exosome composition seems to be cell and tissue specific, they are highly suitable to serve as diagnostic markers.
Our hypothesis is that high expression of the immunotherapeutic targets (CD20, PD-L1) on exosomes derived from aggressive or resistant B-NHL may allow tumor cells to escape therapeutic antibodies, and thus contribute in vivo to therapeutic resistance. For this objective, we will used exosomes derived from DLBCL human cells and exosomes isolated from plasma of DLBCL patients. We will analyze, on these microvesicles, CD20 and PDL-1 expression in function of DLBCL sub-types and outcome of patients. Moreover, exosome capacity to interfere with immunotherapy will be also studied from in vitro and in vivo (xenografts) models.
- Being tested
- blood sample
- Keywords
- B cells, exosomes, immunotherapy, Lymphomas, DLBCL
- Medical subject headings
- Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
blood sampleOther
1 blood volume (5-7 ml EDTA)
| Study group | Role | What they receive |
|---|---|---|
| patients with DLBCL | Experimental | Not described Receives: Other: blood sample |
| Healthy volunteers | Active comparator | Not described Receives: Other: blood sample |
What is being measured
The primary outcome is the main question the study is designed to answer.
Quantification of CD20 and PDL-1 in exosomes purified from cell cultures of DLBCL human cell lines and from Healthy volunteers
From D0 until the end of the inclusion period (36 months)
Measured: Month 36
Secondary outcomes (1)
Evaluation if peripheral exosomes can be used as novel diagnostic biomarkers in DLBCL
To analyze the prognostic value of exosomal markers on therapeutic response and patient outcome, each patient included in the study at diagnostic (D0) will be followed up until 36 months after inclusion.
Measured: Month 36
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jun 2019
- Study start2 Jul 2019
- Primary completion2 Jul 2025
- Study completion2 Jul 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Lymphoma, B-cell, Aggressive Non-Hodgkin (B-NHL)Studies of the same condition, open and under way.
- More trials run by University Hospital, LimogesThe 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
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 90 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Limoges
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03985696
- Sponsor's protocol ID
- 87RI18_0025 (ExoReBLy)
- Acronym
- ExoReBLy
- Status last verified
- Jul 2026
- First submitted
- 11 Jun 2019
- Last updated
- 14 Jul 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Akil H, Bentayeb H, Aitamer M, Vignoles C, Abraham J, Gachard N, Olivrie A, Guyot A, Gobbo J, Feuillard J, Shirvani H, Troutaud D. Analysis of CD20 and PD-L1 levels on small extracellular vesicles (sEV) produced by DLBCL cells and EBV-transformed B cells, and potential role in T cell inhibition. Exp Hematol Oncol. 2024 May 17;13(1):53. doi: 10.1186/s40164-024-00518-2.
PubMed 38760788
Study at a glance
From the registry record, last updated by the sponsor on 14 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Exosomes and Resistance to Immunotherapy in Aggressive Non-Hodgkin B-cell Lymphomas (B-NHL)
- ClinicalTrials.gov ID
- NCT03985696
- Acronym / sponsor ID
- ExoReBLy / 87RI18_0025 (ExoReBLy)
- Keywords
- B cells, exosomes, immunotherapy, Lymphomas, DLBCL
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 90 participants (actual)
- Lead sponsor
- University Hospital, LimogesUniversity, hospital or other
- Study start
- 2 Jul 2019 (actual)
- Primary completion
- 2 Jul 2025 (actual)
- Study completion
- 2 Jul 2025 (actual)
- First posted
- 14 Jun 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.
Diffuse large B-cell lymphomas (DLBCL) are highly aggressive and heterogeneous B-cell lymphoma that would imminently be fatal without treatment. Monoclonal anti-CD20 antibody, rituximab, in combination of CHOP chemotherapy (R-CHOP) is widely used with favourable results. Although more than half of patients achieve long-term remission, many are not cured with this immunotherapy. Suboptimal response and/or resistance to rituximab have remained a challenge in the therapy of DLBCL but also of all B-NHL. Exosomes are microvesicles released from tumor B cells that are found in plasma of patients with B-NHL. Exosomes carry therapeutic targets (as CD20, PDL-1) and could act as "decoy-receptors" for immunotherapy. Our objective is to precise, in aggressive B-NHL, the role of exosomes in immunotherapy escape.
Detailed description
Diffuse large B-cell lymphomas (DLBCL) are highly aggressive and heterogeneous B-cell lymphoma that would imminently be fatal without treatment. Monoclonal anti-CD20 antibody, rituximab, in combination of CHOP chemotherapy (R-CHOP) is widely used with favourable results. Although more than half of patients achieve long-term remission, many are not cured with this immunotherapy. Decreased CD20 expression has been postulated to be one of the most important contributing to rituximab resistance. Moreover, R-CHOP therapies are sometimes ineffective, and new treatment strategies based notably on host immune responses modulation are being explored. Among them, programmed cell death ligand 1 (PD-L1) protein was identified as a potent predicting biomarker in DLBCL. Exosomes are small membrane vesicles secreted by several cell types during exocytic fusion of multivesicular bodies with the plasma membrane. Many cancer cells have been shown to secrete exosomes in greater amounts than normal cells. Exosome secretion may contribute to drug resistance. Indeed, exosome release from B-cell Non-Hodgkin Lymphoma (B-NHL), by the expression of CD20, has been suggest to act as decoy targets upon rituximab exposure, allowing lymphoma cells to escape from humoral immunotherapy. Finally, as exosome composition seems to be cell and tissue specific, they are highly suitable to serve as diagnostic markers.
Our hypothesis is that high expression of the immunotherapeutic targets (CD20, PD-L1) on exosomes derived from aggressive or resistant B-NHL may allow tumor cells to escape therapeutic antibodies, and thus contribute in vivo to therapeutic resistance. For this objective, we will used exosomes derived from DLBCL human cells and exosomes isolated from plasma of DLBCL patients. We will analyze, on these microvesicles, CD20 and PDL-1 expression in function of DLBCL sub-types and outcome of patients. Moreover, exosome capacity to interfere with immunotherapy will be also studied from in vitro and in vivo (xenografts) models.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| patients with DLBCL | Experimental | Other: blood sample |
| Healthy volunteers | Active comparator | Other: blood sample |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- patients over 18 years old with DLBCL at diagnostic or relapsed patients after R-CHOP therapy.
- Healthy volunteers over 18 years old
Key exclusion criteria (1 listed)
- other B cell diseases
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 |
|---|---|---|
| blood sample1 blood volume (5-7 ml EDTA) | Other | Healthy volunteers, patients with DLBCL |
Primary outcome
Quantification of CD20 and PDL-1 in exosomes purified from cell cultures of DLBCL human cell lines and from Healthy volunteers
Time frame: Month 36
From D0 until the end of the inclusion period (36 months)
1 secondary outcome
Evaluation if peripheral exosomes can be used as novel diagnostic biomarkers in DLBCL
Time frame: Month 36
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Jul 2026.
- Results publication: PubMed 38760788Akil H, Bentayeb H, Aitamer M, Vignoles C, Abraham J, Gachard N, Olivrie A, Guyot A, Gobbo J, Feuillard J, Shirvani H, Troutaud D. Analysis of CD20 and PD-L1 levels on small extracellular vesicles (sEV) produced by DLBCL cells and EBV-transformed B cells, and potential role in T cell inhibition. Exp Hematol Oncol. 2024 May 17;13(1):53. doi: 10.1186/s40164-024-00518-2.
- Individual participant dataSharing planned: No
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing blood sample in people with Lymphoma, B-cell, Aggressive Non-Hodgkin (B-NHL), run by University Hospital, Limoges at 1 site in France.
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 2 inclusion and 1 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: finished, as of the sponsor's last update on 14 Jul 2026. 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 France. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Quantification of CD20 and PDL-1 in exosomes purified from cell cultures of DLBCL human cell lines and from Healthy volunteers (time frame: Month 36). 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 NCT03985696, which also lists 1 linked publication.
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 14 Jul 2026.