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)

August 12, 2026 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

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Patients receive ibrutinib 420 mg daily for 3 months before CAR T-cell infusion. Obinutuzumab 1000 mg is administered 14 days before leukapheresis to reduce circulating CLL cells. Lymphodepletion consists of fludarabine 25 mg/m² and cyclophosphamide 250 mg/m² on days -5 to -3. In a 3+3 dose-escalation design, patients receive a single infusion of 25 × 10⁶ (DL1), 50 × 10⁶ (DL2), or 100 × 10⁶ (DL3) autologous CD19 CAR T cells. Lenalidomide 10 mg is administered orally on days 0 through 6. At day 28, patients with measurable residual disease (MRD)-positive disease are eligible for lenalidomide 10 mg 1-14 days per os plus obinutuzumab 1000 mg IV 1,8,15 days on cycle 1 and on day 1 on 2-6 cycles consolidation, whereas patients with MRD-negative disease receive lenalidomide 10 mg per os 1-14 days maintenance for 3 cycles.

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.
  • Progression-free survival rates.
  • Overall survival rates.
  • MRD negativity rates measured by flow cytometry.

Study Type

Interventional

Enrollment (Estimated)

24

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 Contact

Study Locations

  • Belarus
    • Select A State
      • Vitebsk, Select A State, Belarus, 210023
        • Recruiting
        • Hematology/Oncology department
        • Contact:

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 Lenalidomide

Phase 1: Determine safety of IL-7/IL-15 expanded 25x10^6 antiCD19 CAR-T cells with concomitant Lenalidomide 10 mg per os days 0-6 in patients with relapsed/refractory CLL. Patients will be enrolled in a 3+3 fashion. At day 28, patients with measurable residual disease (MRD)-positive disease are eligible for lenalidomide 10 mg 1-14 days per os plus obinutuzumab 1000 mg IV 1,8,15 days on cycle 1 and on day 1 on 2-6 cycles consolidation, whereas patients with MRD-negative disease receive lenalidomide 10 mg per os 1-14 days maintenance for 3 cycles.

3 patients per cohort.
Drug: Lenalidomide
Lenalidomide 10mg per os 0- 6 days
Other Names:
  • Revlimid
Drug: Lenalidomide
Lenalidomide 10 mg per os 1 -14 days
Other Names:
  • Revlimid
Biological: Obinutuzumab Injection [Gazyva]
Combined with Lenalidomide 10 mg per os 1- 14 days for 6 cycles
Experimental: Medium dose of antiCD19 CAR T-cell therapy plus Lenalidomide
Phase 1: Phase 1: Determine safety of IL-7/IL-15 expanded 50x10^6 antiCD19 CAR-T cells with concomitant Lenalidomide 10 mg per os days 0-6 in patients with relapsed/refractory CLL. Patients will be enrolled in a 3+3 fashion. At day 28, patients with measurable residual disease (MRD)-positive disease are eligible for lenalidomide 10 mg 1-14 days per os plus obinutuzumab 1000 mg IV 1,8,15 days on cycle 1 and on day 1 on 2-6 cycles consolidation, whereas patients with MRD-negative disease receive lenalidomide 10 mg per os 1-14 days maintenance for 3 cycles. 3 patients per cohort.
Drug: Lenalidomide
Lenalidomide 10mg per os 0- 6 days
Other Names:
  • Revlimid
Drug: Lenalidomide
Lenalidomide 10 mg per os 1 -14 days
Other Names:
  • Revlimid
Biological: Obinutuzumab Injection [Gazyva]
Combined with Lenalidomide 10 mg per os 1- 14 days for 6 cycles
Experimental: High dose antiCD19 CAR T-cell therapy plus Lenalidomide
Phase 1: Phase 1: Determine safety of IL-7/IL-15 expanded 100x10^6 antiCD19 CAR-T cells with concomitant Lenalidomide 10 mg per os days 0-6 in patients with relapsed/refractory CLL. Patients will be enrolled in a 3+3 fashion. At day 28, patients with measurable residual disease (MRD)-positive disease are eligible for lenalidomide 10 mg 1-14 days per os plus obinutuzumab 1000 mg IV 1,8,15 days on cycle 1 and on day 1 on 2-6 cycles consolidation, whereas patients with MRD-negative disease receive lenalidomide 10 mg per os 1-14 days maintenance for 3 cycles. 9 patients per cohort.
Drug: Lenalidomide
Lenalidomide 10mg per os 0- 6 days
Other Names:
  • Revlimid
Drug: Lenalidomide
Lenalidomide 10 mg per os 1 -14 days
Other Names:
  • Revlimid
Biological: Obinutuzumab Injection [Gazyva]
Combined with Lenalidomide 10 mg per os 1- 14 days for 6 cycles

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Adverse events incidence
Time Frame: 24 months
24 months
Safety
Time Frame: 24 months
  • 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.
24 months

Secondary Outcome Measures

Outcome Measure
Time Frame
Efficacy
Time Frame: - Overall response rate, including complete response (CR) and partial response (PR) rates. - Progression-free survival rates. - Overall survival rates. - MRD negativity rates measured by flow cytometry.
- Overall response rate, including complete response (CR) and partial response (PR) rates. - Progression-free survival rates. - Overall survival rates. - MRD negativity rates measured by flow cytometry.

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)

May 14, 2024

Primary Completion (Estimated)

August 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)

January 7, 2025

Study Record Updates

Last Update Posted (Actual)

August 13, 2026

Last Update Submitted That Met QC Criteria

August 12, 2026

Last Verified

August 1, 2026

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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