Chronic Lymphocytic Leukemia, CLL
Conditions
Brief summary
In this biological study, blood samples will be collected from patients with CLL treated with targeted agents (ibrutinib and venetoclax) to assess the impact of these treatments on the generation of CAR T cells in terms of manufacturing efficiency, immunophenotypic characteristics and functional properties.
Detailed description
This is a biological study aimed at analyzing the features of CAR T cells generated in CLL patients treated with ibrutinib or venetoclax. To this purpose, blood samples will be collected from patients with CLL before starting therapy with ibrutinib or venetoclax and after 6 and 12 months of treatment. Anti-CD19 CAR T cells will be generated and tested for: (i) viability, expansion and generation efficiency; (ii) phenotypic characteristics, in terms of CD4/CD8 composition, differentiation subset distribution, exhaustion markers and expression of immune checkpoint molecules; (iii) in vitro functional properties, in terms of proliferation ability, cytokines production, cytotoxic activity and killing of target cells. CAR T cells produced from the same patient at different timepoints will be compared. Phenotypic and functional data on CAR T cells will be also correlated with main CLL prognostic factors (e.g. IGHV mutational status, FISH abnormalities, TP53 mutation status) and outcome variables (response status, duration of response).
Interventions
OTHERPeripheral blood samples withdrawal
Peripheral blood samples evaluation
Sponsors
Gruppo Italiano Malattie EMatologiche dell'Adulto
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosis of CLL/SLL meeting the IWCLL 2008 criteria; * ≥18 years old; * Indication for treatment with targeted therapies (i.e. ibrutinib or venetoclax); * Anticipated possibility to collect blood samples at the baseline and at 6- and 12-month timepoints; * Signed written informed consent according to ICH/EU/GCP and national local laws; * Confirmed availability of the laboratory to enroll and to process patient samples.
Exclusion criteria
* Expected treatment duration with targeted drug \< 12 months, according to treating physician; * Previously treated with more than 2 lines of CLL-directed therapy; * Concurrent use of systemic steroids or chronic use of immunosuppressive medications; * Active HBV (HBsAg+ or HBV DNA+) or HCV or HIV infection.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cell killing rate of anti-CD19 CAR T cells | After 12 months of treatment | Assessment of the cytotoxic functions of anti-CD19 CAR T cells generated from CLL patients in terms of cell killing rate before and during treatment with targeted agents (i.e. ibrutinib or venetoclax). |
Countries
Italy
Contacts
Primary ContactPaola Fazi
Backup ContactEnrico Crea
Outcome results
None listed