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.

NCT06762431 | Recruiting Phase 1 DMC

• 1 other identifier: VTB-CLL002
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Chronic Lymphocytic Leukaemia (CLL); Small Lymphocytic Lymphoma (SLL)

Keywords

anti-CD19 CAR T-cells; Lenalidomide; Ibrutinib

Outcome Measures

Primary Outcomes (2)

• Adverse events incidence

  24 months

• Safety

  * 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 Outcomes (1)

• Efficacy

  - 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 Arms (3)

Low dose antiCD19 CAR T-cells plus Lenalidomide

EXPERIMENTAL

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; Biological: Obinutuzumab Injection [Gazyva]

Medium dose of antiCD19 CAR T-cell therapy plus Lenalidomide

EXPERIMENTAL

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; Biological: Obinutuzumab Injection [Gazyva]

High dose antiCD19 CAR T-cell therapy plus Lenalidomide

EXPERIMENTAL

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; Biological: Obinutuzumab Injection [Gazyva]

Interventions

Lenalidomide DRUG

Lenalidomide 10mg per os 0- 6 days

Also known as: Revlimid

High dose antiCD19 CAR T-cell therapy plus Lenalidomide; Low dose antiCD19 CAR T-cells plus Lenalidomide; Medium dose of antiCD19 CAR T-cell therapy plus Lenalidomide

Obinutuzumab Injection [Gazyva] BIOLOGICAL

Combined with Lenalidomide 10 mg per os 1- 14 days for 6 cycles

High dose antiCD19 CAR T-cell therapy plus Lenalidomide; Low dose antiCD19 CAR T-cells plus Lenalidomide; Medium dose of antiCD19 CAR T-cell therapy plus Lenalidomide

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Vitebsk Regional Clinical Cancer Centre: lead
• Republican Scientific and Practical Center for children's Oncology, Hematology and Immunology: collaborator

Study Sites (1)

Hematology/Oncology department

Vitebsk, Select A State, 210023, Belarus

RECRUITING

MeSH Terms

Conditions

Leukemia, B-Cell; Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

Lenalidomide; obinutuzumab

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Central Study Contacts

Mikalai Katsin

CONTACT

80297188691; oncogemvocod@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief of Hematology/Oncology department

Study Record Dates

• First Submitted: December 30, 2024
• First Posted: January 7, 2025
• Study Start: November 4, 2024
• Primary Completion: August 9, 2026
• Study Completion (Estimated): August 31, 2026
• Last Updated: August 10, 2026

Record last verified: 2026-08

Locations

BE (1)