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

January 3, 2022 updated by: Gruppo Italiano Malattie EMatologiche dell'Adulto

Impact of Treatment With Targeted Therapies on the Generation of Effective CAR T Cells in Patients With Chronic Lymphocytic Leukemia

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Anticipated)

23

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Italy
      • Milano, Italy
        • Recruiting
        • Irccs Ospedale S. Raffaele - Milano - Unità Neoplasie Linfocitarie B
        • Contact:
      • Torino, Italy
        • Recruiting
        • Aou Città Della Salute E Della Scienza, Ospedale S. Giovanni Battista Molinette - Torino - Sc Ematologia - Università Degli Studi Di Torino

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Other: CAR T Cells generation
CAR T Cells generation at baseline and after 6 and 12 months of treatment
Other: Peripheral blood samples withdrawal
Peripheral blood samples evaluation

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Cell killing rate of anti-CD19 CAR T cells
Time Frame: 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).
After 12 months of treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Gruppo Italiano Malattie EMatologiche dell'Adulto

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 1, 2021

Primary Completion (Anticipated)

October 1, 2024

Study Completion (Anticipated)

October 1, 2024

Study Registration Dates

First Submitted

November 9, 2020

First Submitted That Met QC Criteria

November 18, 2020

First Posted (Actual)

November 23, 2020

Study Record Updates

Last Update Posted (Actual)

January 4, 2022

Last Update Submitted That Met QC Criteria

January 3, 2022

Last Verified

October 1, 2021

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CLL2020

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

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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