Trials / Recruiting

RecruitingNCT06213636

Fourth-gen CAR T Cells Targeting CD19/CD22 for Highly Resistant B-cell Lymphoma/Leukemia (PMBCL/CNS-BCL).

T-cell Infusion Targeting CD19 and CD22 for Refractory/Relapsed Leukemia/Lymphoma Patients With or Without Central Nervous System Involvement

Status: Recruiting
Phase: Phase 1 / Phase 2
Study type: Interventional
Enrollment: 75 (estimated)

Sponsor: Essen Biotech · Academic / Other
Sex: All
Age: 2 Years – 90 Years
Healthy volunteers: Not accepted

Summary

This is an open-label, single-arm, phase I clinical trial with dose escalation designed to investigate the safety, tolerability, and pharmacokinetic properties of Human CD19-CD22 Targeted T Cells Infusion. The primary objectives are to preliminarily assess the impact of Human CD19-CD22 Targeted T Cells Infusion in patients with relapsed/refractory B-cell acute lymphoblastic leukemia and to explore the appropriate dose and reinfusion schedule for phase II. Eligible participants, including those with Central Nervous System Lymphoma, B Cell Lymphoma (BCL), Acute Lymphocytic Leukemia (ALL), Acute Lymphoblastic Leukemia (ALL), B Acute Lymphoblastic Leukemia (B-ALL), Refractory Non-Hodgkin Lymphoma, Refractory Chronic Lymphocytic Leukemia (CLL), Refractory B Acute Lymphoblastic Leukemia (B-ALL), Diffuse Large B Cell Lymphoma, Lymphoid Leukemia, and MRD-positive cases, can participate. Eligibility will be determined through a comprehensive assessment, including disease evaluations, a physical examination, Electrocardiograph, Computed Tomography (CT), Magnetic Resonance Imaging (MRI), Positron Emission Tomography (PET), and blood tests. Prior to the infusion of CD19-CD22 CAR+ T cells, participants will undergo chemotherapy. After the infusion, participants will be closely monitored for potential side effects and the effectiveness of CD19-CD22 CAR+ T cells. Certain study procedures may be conducted during hospitalization.

Detailed description

This clinical trial involves the use of Chimeric Antigen Receptor T-cell (CAR-T) therapy targeting CD19 and CD22 in patients with various hematologic malignancies, including B-cell acute lymphoblastic leukemia (B-ALL), B-cell lymphomas, refractory non-Hodgkin lymphoma, chronic lymphocytic leukemia (CLL), diffuse large B-cell lymphoma (DLBCL), lymphoid leukemia, and cases positive for minimal residual disease (MRD). CD19 and CD22 are cell surface molecules commonly found on B cells, and their targeted therapy using CAR-T cells has shown promise in the treatment of these malignancies. Intervention: The intervention in this clinical trial involves the infusion of Human CD19-CD22 Targeted T Cells, which have been genetically engineered to express chimeric antigen receptors specific to CD19 and CD22. These CAR-T cells are designed to recognize and bind to CD19 and CD22 molecules on the surface of malignant B cells, leading to their destruction. The infusion of CAR-T cells will be administered to eligible participants as part of their treatment regimen. Objectives: The primary objectives of this intervention are as follows: To evaluate the safety and tolerability of the CD19 and CD22 CAR-T cell therapy. To assess the pharmacokinetic characteristics of the infused CAR-T cells. To preliminarily observe the clinical effectiveness of CD19 and CD22 CAR-T cell therapy in various hematologic malignancies, including B-ALL, B-cell lymphomas, refractory non-Hodgkin lymphoma, CLL, DLBCL, lymphoid leukemia, and MRD-positive cases. To determine the clinically applicable dose and reinfusion regimen for phase II trials. Mechanism of Action: CD19 and CD22 are cell surface antigens commonly expressed on B-cell malignancies. The CD19-CD22 CAR-T cells are engineered to express a chimeric antigen receptor composed of an extracellular domain that recognizes CD19 and CD22, a transmembrane domain, and intracellular signaling domains. When these modified T cells encounter B cells expressing CD19 and CD22, the CAR-T cells are activated, leading to their binding to the malignant B cells. This binding triggers a cytotoxic response, resulting in the destruction of the target B cells. Treatment Regimen: Prior to the infusion of CD19-CD22 CAR-T cells, participants will undergo preconditioning chemotherapy. This chemotherapy serves to prepare the patient's immune system for the CAR-T cell therapy. Following chemotherapy, participants will receive the infusion of CD19-CD22 CAR-T cells. Monitoring and Follow-up: After the CAR-T cell infusion, participants will be closely monitored for side effects and adverse events. Additionally, the clinical response and effectiveness of CD19-CD22 CAR-T cells in controlling the malignancy will be assessed through various evaluations, including disease assessments, imaging studies (CT, MRI, PET), and blood tests. These assessments may be performed while participants are hospitalized. Rationale: CD19 and CD22 are well-established targets for CAR-T cell therapy in B-cell malignancies. By targeting both CD19 and CD22, this approach aims to maximize the therapeutic benefit and expand the applicability of CAR-T therapy to a broad spectrum of hematologic malignancies. The rationale behind this clinical trial is to further evaluate the safety, efficacy, and optimal dosing regimens of CD19 and CD22 CAR-T cells in various patient populations with these malignancies. Ultimately, the goal is to provide a promising treatment option for patients with relapsed/refractory B-cell malignancies, including those with central nervous system involvement, who have limited therapeutic alternatives.

Conditions

Interventions

Type	Name	Description
BIOLOGICAL	CD19/CD22-CAR T cells	The intervention in this clinical trial involves a novel approach using CD19/CD22-Chimeric Antigen Receptor T (CAR T) cells combined with chemotherapy. The goal is to assess safety and efficacy in patients with specific hematologic malignancies. Treatment Regimen: Patients in the trial will undergo the following regimen: Fludarabine Phosphate (Days -4 to -2): IV administration of fludarabine phosphate over 30 minutes on days -4 to -2. It's part of the preparatory regimen to enhance the body's response to CAR T-cell therapy. Cyclophosphamide (Day -2): IV cyclophosphamide over 60 minutes on day -2. CD19/CD22-Chimeric Antigen Receptor T Cells (Day 0): IV administration of investigational therapy, CD19/CD22-CAR T cells, over 10-20 minutes on day 0. Additional Doses: Eligible patients responding well to the initial CD19/CD22-CAR T cell infusion without unacceptable side effects and sufficient CAR T cell availability may receive 2 or 3 additional doses.

Timeline

Start date: 2024-07-10
Primary completion: 2027-02-10
Completion: 2028-12-10
First posted: 2024-01-19
Last updated: 2025-08-06

Locations

1 site across 1 country: China

Source: ClinicalTrials.gov record NCT06213636. Inclusion in this directory is not an endorsement.