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

NCT ID: NCT04640909

Last Updated: 2022-01-04

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 23 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-10-01
• Study Completion Date: 2024-10-31

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).

Conditions

CLL; Chronic Lymphocytic Leukemia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

CAR T Cells generation

CAR T Cells generation at baseline and after 6 and 12 months of treatment

Group Type: OTHER

Peripheral blood samples withdrawal

Intervention Type: OTHER

Peripheral blood samples evaluation

Interventions

Peripheral blood samples withdrawal

Peripheral blood samples evaluation

Intervention Type: OTHER

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Gruppo Italiano Malattie EMatologiche dell'Adulto

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Irccs Ospedale S. Raffaele - Milano - Unità Neoplasie Linfocitarie B

Milan, , Italy

Site Status: RECRUITING

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

Torino, , Italy

Site Status: RECRUITING

Countries

Italy

Central Contacts

Paola Fazi

Role: CONTACT

p.fazi@gimema.it

0670390528

Enrico Crea

Role: CONTACT

e.crea@gimema.it

0670390514

Facility Contacts

Lydia Scarfò

Role: primary

scarfo.lydia@hsr.it

3476866923

Marta Coscia

Role: primary

marta.coscia@unito.it

Other Identifiers

CLL2020

Identifier Type: -

Identifier Source: org_study_id