- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05888701
"Don't Eat me" Signal in Hematological Malignancies: CD24 as New Target to Improve Anti-cancer Immunity.
Study Overview
Status
Detailed Description
MCL is an aggressive B-NHL with dismal prognosis with high probability of relapse after conventional immunochemotherapeutic regimen. CLL is instead an incurable chronic B-cell malignancy with higher probability of relapse after several lines of conventional therapies and a non-negligible risk of progression into an aggressive lymphoma. Further approaches are needed to provide valid alternatives for these relapsed and refractory diseases. In these two settings, TME is known to be involved in cancer cell survival and confers a negative impact on standard treatment efficacy and adoptive T cell immunity, for which new immunotherapeutic agents could be an alternative approach in case of poor prognostic settings. Within TME, TAM are involved in improving tumor growth survival in MCL and CLL, dampening immunotherapy as well. Anti-CD47 mAb turned out to be a consistent DEMs that, once blocked, is able to improve phagocytosis and clearance of tumor cells in blood cancer. CD24 has been recently validated as another DEMs in preclinical analysis in solid cancer. Since CD24 is expressed during early phase of B-cell differentiation, MCL and CLL might take advantage of the blockade of this signal, since TAM and NCLs are strictly interconnected with their corresponding tumoral cells, providing tumor cell proliferation and immune escape.
To fulfill the purposes of this project, collection of leftover patient-derived samples will be routinary performed at the time of diagnosis and at the time of relapse of the disease, in this latter case with the aim to check any CD24, CD47 and CD20 surface expression modification on B-cell blasts (e.g., clone selection with CD24/CD47 upregulation after conventional regimen), SIRP-α and Siglec-10 expression on patient-derived Monocyte/Macrophage system (expressing higher levels of DEMs ligands as potential mechanism of resistance after conventional therapy).
Furthermore, phagocytosis assays with samples obtained at the time of relapse will be compared with the equivalent experiments performed with the samples collected at the time of diagnosis to evaluate any potential differences.
As previously described, phagocytosis analysis will be based on a co-culture process that involves the use of the anti-CD24 antibody (alone or in combination with other antibodies described in the secondary endpoint) incubating with macrophages (from healthy donor or from patient) and patient tumor cells (MCL or CLL), this latter labeled with a fluorescent substance (i.e., CFSE). Macrophage staining (with anti-CD11b-PE antibody) and subsequent flow cytometric analysis will be performed: the ratio between double stained macrophages (CD11b-PE+/CFSE+) and single stained macrophages (CD11b-PE+) will provide the entity of phagocytosis, which will be compared with the negative control and the other experimental conditions (antibody combinations described later in the secondary endpoints). The double staining of macrophages provides indirect results of phagocytosis (if the macrophage phagocytes CFSE+ cells, it will also acquire this staining in addition to that due to the anti-CD11b-PE antibody).
Finally, donor-derived macrophages will be isolated from PBMC obtained from leftover peripheral blood which remained within the circuit used for plateletpheresis of healthy donors. As a matter of fact, residual blood (almost 15 ml) can be found in the reservoir of this circuit that is normally trashed after the procedure. Donors will sign informed consent for use of leftover material for research purposes and this project in particular.
Study Type
Enrollment (Estimated)
Contacts and Locations
Study Contact
- Name: Andrea Aroldi
- Phone Number: + 39 0392339065
- Email: andrea.aroldi@asst-monza.it
Study Locations
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MB
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Monza, MB, Italy, 20900
- Recruiting
- Andrea Aroldi
-
Contact:
- Andrea Aroldi
- Phone Number: +39 0392339065
- Email: andrea.aroldi@asst-monza.it
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Adult
- Older Adult
Accepts Healthy Volunteers
Sampling Method
Study Population
Description
Inclusion Criteria:
Patient inclusion criteria:
- Signed and dated EC-approved informed consent
- Diagnosis of Mantle-cell Lymphoma (MCL) or B-cell Chronic Lymphocytic Leukemia (CLL) defined according to World Health Organization (WHO) criteria.
- Female or male, 18 years of age or older.
- ECOG performance status 0-3.
- Willingness and ability to comply with routine clinical practice and study procedures.
Donors inclusion criteria:
- Signed and dated EC-approved informed consent.
- Healthy volunteers agreed to undergo plateletpheresis.
- Female or male, 18 years of age or older.
- Willingness and ability to comply with Transfusion Medicine clinical practice and study procedures.
Exclusion Criteria
Patient exclusion criteria:
- Other hematological diseases defined by WHO criteria different from MCL and CLL.
- Previous treatment regimens that included allogeneic stem cell transplantation (ASCT).
Donors exclusion criteria:
-Healthy volunteers agreed to perform any kind of donations with the exception of plateletpheresis.
Study Plan
How is the study designed?
Design Details
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Primary endopoint
Time Frame: 36 months
|
Rate of phagocytosis of human M2-like macrophages co-cultured with MCL and CLL blast cells treated with anti-CD24 mAb.
|
36 months
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Secondary endopoints
Time Frame: 36 months
|
|
36 months
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Andrea Aroldi, Ospedale San Gerardo - Asst Monza
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Pathologic Processes
- Immune System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lymphoproliferative Disorders
- Lymphatic Diseases
- Immunoproliferative Disorders
- Lymphoma, Non-Hodgkin
- Neoplasms by Site
- Disease Attributes
- Hematologic Diseases
- Leukemia, Lymphoid
- Leukemia
- Leukemia, B-Cell
- Lymphoma
- Chronic Disease
- Hematologic Neoplasms
- Lymphoma, Mantle-Cell
- Leukemia, Lymphocytic, Chronic, B-Cell
Other Study ID Numbers
- CD24.DEM
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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