Clinical trial NCT06762431: 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.
Official title: 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.
Study type: INTERVENTIONAL
Overall status: ENROLLING_BY_INVITATION
Phase: PHASE1
PHASE2
Conditions: Chronic Lymphocytic Leukaemia (CLL)
Small Lymphocytic Lymphoma (SLL)
Keywords: anti-CD19 CAR T-cells
Lenalidomide
Ibrutinib
Lead sponsor: Vitebsk Regional Clinical Cancer Centre
Sponsor class: OTHER
Collaborators: name: Republican Scientific and Practical Center for children's Oncology, Hematology and Immunology
First posted: 2025-01-07
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Adverse events incidence
timeFrame: 24 months
Secondary outcomes:
Other outcomes:
Locations:
city: Vitebsk
country: Belarus
facility: Hematology/Oncology department
state: Select a State
Study officials:
References: