Clinical trial NCT04640909: Impact of Treatment With Targeted Therapies on the Generation of CAR T Cells in CLL Patients
Official title: Impact of Treatment With Targeted Therapies on the Generation of Effective CAR T Cells in Patients With Chronic Lymphocytic Leukemia
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: CLL
Chronic Lymphocytic Leukemia
Lead sponsor: Gruppo Italiano Malattie EMatologiche dell'Adulto
Sponsor class: OTHER
First posted: 2020-11-23
Enrollment: 23
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

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).

Eligibility criteria: 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.

Primary outcomes:
measure: Cell killing rate of anti-CD19 CAR T cells
timeFrame: After 12 months of treatment
Secondary outcomes:
Other outcomes:
Locations:
city: Milano
country: Italy
facility: Irccs Ospedale S. Raffaele - Milano - Unità Neoplasie Linfocitarie B
city: Torino
country: Italy
facility: Aou Città Della Salute E Della Scienza, Ospedale S. Giovanni Battista Molinette - Torino - Sc Ematologia - Università Degli Studi Di Torino
Study officials:
References: