Phase I/II Open-label Study Evaluating The Safety And Efficacy of Concomitant Administration of Anti-CD19 CAR T-cell Therapy and Lenalidomide in Refractory/Relapsed Chronic Lymphocytic Leukemia Patients. (VTB-CLL002)

December 30, 2024 updated by: Mikalai Katsin, Vitebsk Regional Clinical Cancer Centre
This is a Phase I/II interventional, open-label treatment study designed to evaluate the safety and efficacy of concomitant therapy with anti-CD19 CAR T-cells and Lenalidomide in adult patients with relapsed/refractory chronic lymphocytic leukemia (CLL) who have been pretreated with Ibrutinib for 3 months prior to leukapheresis.

Study Overview

Status

Enrolling by invitation

Conditions

Intervention / Treatment

Detailed Description

This is a single-center, open-label study. After meeting the eligibility criteria and enrolling in the trial, patients will take Ibrutinib for 3 months up to Day -1. Leukapheresis for the collection of autologous lymphocytes will take place 2-3 weeks before Day 0. Once the cells have been manufactured, patients will proceed to lymphodepleting chemotherapy with cyclophosphamide and fludarabine from Days -5 to -3, followed by the infusion of anti-CD19-4-1BB-CD3z CAR T-cells at two fixed dose levels: DL1 (50 x 10^6 cells) and DL2 (150 x 10^6 cells), concomitantly with Lenalidomide intake. Lenalidomide maintenance at the dose of 25 mg will be administered from Day +30 for 3 months.

The main purposes of the Phase I part are:

  • To preliminarily explore the safety (incidence of CRS, ICANS, HLH, infections, late ICAHT, and cytopenias) and tolerability.
  • To explore the pharmacokinetics of CAR-T cells.

The main purposes of the Phase II part are:

  • Overall response rate, including complete response (CR) and partial response (PR) rates.
  • Duration of response (DOR).
  • Progression-free survival rates.
  • Overall survival rates.
  • MRD negativity rates measured by flow cytometry.

Study Type

Interventional

Enrollment (Estimated)

60

Phase

  • Phase 2
  • Phase 1

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

  • Belarus
    • Select a State
      • Vitebsk, Select a State, Belarus, 210023
        • Hematology/Oncology department

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

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Documented CD19+ CLL or SLL
  • Patients must have failed at least 1 prior regimen
  • Patients must be currently receiving ibrutinib for at least 3 months prior to enrollment in the study and:
  • Not experiencing any ≥ grade 2 non-hematologic ibrutinib-related toxicity
  • ECOG Performance status 0 or 1
  • 18 years of age and older
  • Adequate organ system function including:

Creatinine < 1.6 mg/dl ALT/AST < 3x upper limit of normal Total Bilirubin <2.0 mg/dl with the exception of patients with Gilbert syndrome; patients with Gilbert syndrome may be included if their total bilirubin is ≥ 3.0 x ULN and direct bilirubin ≤ 1.5 x ULN.

  • Have no active GVHD and require no immunosuppression
  • Are more than 6 months from transplant
  • No contraindications for leukapheresis
  • Left Ventricular Ejection fraction >50%
  • Gives informed consent

Exclusion Criteria:

  • CLL patients with known or suspected transformed disease (i.e. Richter's transformation).
  • Pregnant or lactating women.
  • Uncontrolled active infection.
  • Active hepatitis B or hepatitis C infection.
  • Concurrent use of systemic steroids or chronic use of immunosuppressant medications.
  • Any uncontrolled active medical disorder
  • HIV infection.
  • Patients with active CNS involvement with malignancy.
  • Class III/IV cardiovascular disability according to the New York Heart Association Classification.
  • Subjects with clinically apparent arrhythmia or arrhythmias who are not stable

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: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Low dose antiCD19 CAR T-cells plus low dose Lenalidomide

Phase 1: Determine safety of IL-7/IL-15 expanded 50x10^6 antiCD19 CAR-T cells with concomitant low dose Lenalidomide in patients with relapsed/refractory CLL. Patients will be enrolled in 3+3 fashion.

Phase 1b: Six to nine patient expansion cohorts. If six patients are enrolled in Phase 1 then only six additional patients will be added. If three patients are enrolled in Phase 1 then nine additional patients will be treated for a total of 12 patients.
Drug: Lenalidomide
Dose Level 1
Other Names:
  • Revlimid
Drug: Lenalidomide
Dose Level 2
Other Names:
  • Revlimid
Experimental: Low dose antiCD19 CAR T-cell therapy plus high dose Lenalidomide
Phase 1: Determine safety of IL-7/IL-15 expanded 50x10^6 antiCD19 CAR-T cells with concomitant high dose Lenalidomide in patients with relapsed/refractory CLL. Patients will be enrolled in 3+3 fashion. Phase 1b: Six to nine patient expansion cohorts. If six patients are enrolled in Phase 1 then only six additional patients will be added. If three patients are enrolled in Phase 1 then nine additional patients will be treated for a total of 12.
Drug: Lenalidomide
Dose Level 1
Other Names:
  • Revlimid
Drug: Lenalidomide
Dose Level 2
Other Names:
  • Revlimid
Experimental: High dose antiCD19 CAR T-cell therapy plus low dose Lenalidomide
Phase 1: Determine safety of IL-7/IL-15 expanded 150x10^6 antiCD19 CAR-T cells with concomitant low dose Lenalidomide in patients with relapsed/refractory CLL. Patients will be enrolled in 3+3 fashion. Phase 1b: Six to nine patient expansion cohorts. If six patients are enrolled in Phase 1 then only six additional patients will be added. If three patients are enrolled in Phase 1 then nine additional patients will be treated for a total of 12.
Drug: Lenalidomide
Dose Level 1
Other Names:
  • Revlimid
Drug: Lenalidomide
Dose Level 2
Other Names:
  • Revlimid
Experimental: High dose antiCD19 CAR T-cell therapy plus high dose Lenalidomide
Phase 1: Determine safety of IL-7/IL-15 expanded 150x10^6 antiCD19 CAR-T cells with concomitant high dose Lenalidomide in patients with relapsed/refractory CLL. Patients will be enrolled in 3+3 fashion. Phase 1b: Six to nine patient expansion cohorts. If six patients are enrolled in Phase 1 then only six additional patients will be added. If three patients are enrolled in Phase 1 then nine additional patients will be treated for a total of 12.
Drug: Lenalidomide
Dose Level 1
Other Names:
  • Revlimid
Drug: Lenalidomide
Dose Level 2
Other Names:
  • Revlimid

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Adverse events incidence
Time Frame: 24 months
24 months

Collaborators and Investigators

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

Sponsor

Vitebsk Regional Clinical Cancer Centre

Collaborators

Republican Scientific and Practical Center for children's Oncology, Hematology and Immunology

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)

November 4, 2024

Primary Completion (Estimated)

March 9, 2026

Study Completion (Estimated)

August 31, 2026

Study Registration Dates

First Submitted

December 30, 2024

First Submitted That Met QC Criteria

December 30, 2024

First Posted (Actual)

March 25, 2025

Study Record Updates

Last Update Posted (Actual)

March 25, 2025

Last Update Submitted That Met QC Criteria

December 30, 2024

Last Verified

December 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • VTB-CLL002

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

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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