Impact of Treatment With Targeted Therapies on the Generation of CAR T Cells in CLL Patients

Not Applicable

Recruiting

• Conditions: Chronic Lymphocytic Leukemia; CLL
• Interventions: Other: Peripheral blood samples withdrawal

• Registration Number: NCT04640909
• Lead Sponsor: Gruppo Italiano Malattie EMatologiche dell'Adulto

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).

Study Timeline

• Study First Submitted: 2020-11-09
• Study First Submitted QC: 2020-11-18
• Study First Posted: 2020-11-23
• Status Verified: 2021-10
• Study Start: 2021-10-01
• Last Update Submitted: 2022-01-03
• Last Update Posted: 2022-01-04
• Primary Completion: 2024-10
• Study Completion: 2024-10

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 23

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
CAR T Cells generation	Peripheral blood samples withdrawal	CAR T Cells generation at baseline and after 6 and 12 months of treatment

Primary Outcome Measures

Name	Time	Method
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).

Trial Locations

Locations (2)

Irccs Ospedale S. Raffaele - Milano - Unità Neoplasie Linfocitarie B; 🇮🇹 Milano, Italy

Aou Città Della Salute E Della Scienza, Ospedale S. Giovanni Battista Molinette - Torino - Sc Ematologia - Università Degli Studi Di Torino; 🇮🇹 Torino, Italy