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.

Phase 2Enrolling By InvitationNCT06762431

Vitebsk Regional Clinical Cancer Centre60 enrolled

Overview

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.

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

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

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.

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes