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Exosomes and Immunotherapy in Non-Hodgkin B-cell Lymphomas (ExoReBLy)

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ClinicalTrials.gov Identifier: NCT03985696
Recruitment Status : Recruiting
First Posted : June 14, 2019
Last Update Posted : July 8, 2019
Sponsor:
Information provided by (Responsible Party):
University Hospital, Limoges

Tracking Information
First Submitted Date  ICMJE June 11, 2019
First Posted Date  ICMJE June 14, 2019
Last Update Posted Date July 8, 2019
Actual Study Start Date  ICMJE July 2, 2019
Estimated Primary Completion Date July 2, 2025   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 11, 2019)
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)
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03985696 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: June 11, 2019)
Evaluation if peripheral exosomes can be used as novel diagnostic biomarkers in DLBCL [ Time Frame: Month 36 ]
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.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Exosomes and Immunotherapy in Non-Hodgkin B-cell Lymphomas
Official Title  ICMJE Exosomes and Resistance to Immunotherapy in Aggressive Non-Hodgkin B-cell Lymphomas (B-NHL)
Brief 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. 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 Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Condition  ICMJE Lymphoma, B-cell, Aggressive Non-Hodgkin (B-NHL)
Intervention  ICMJE Other: blood sample
1 blood volume (5-7 ml EDTA)
Study Arms  ICMJE
  • Experimental: patients with DLBCL
    Intervention: Other: blood sample
  • Active Comparator: Healthy volunteers
    Intervention: Other: blood sample
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: June 11, 2019)
75
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE July 2, 2025
Estimated Primary Completion Date July 2, 2025   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria :

  • patients over 18 years old with DLBCL at diagnostic or relapsed patients after R-CHOP therapy.
  • Healthy volunteers over 18 years old

Exclusion Criteria:

  • other B cell diseases
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE
Contact: Julie ABRAHAM, Dr +33 (0) 555 056 651 julie.abraham@chu-limoges.fr
Contact: Danielle TROUTAUD, Pr danielle.troutaud@unilim.fr
Listed Location Countries  ICMJE France
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03985696
Other Study ID Numbers  ICMJE 87RI18_0025 (ExoReBLy)
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party University Hospital, Limoges
Study Sponsor  ICMJE University Hospital, Limoges
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account University Hospital, Limoges
Verification Date July 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP