Multi-CAR T Cell Therapy Targeting CD7-positive Malignancies

Acute Myeloid Leukemia Clinical Trial

Official title: A Multi-Center Study of Multiple CAR T Cell Therapy for CD7-positive Hematological Malignancies

Status Recruiting

Clinical Trial Summary

The purpose of this clinical trial is to assess the feasibility, safety and efficacy of CAR T cell therapy against CD7-positive hematological malignancies using CD7 specific CAR T cells. The study also aims to learn more about the function of CD7 CAR T cells and their persistence in patients of hematological malignancies.

Clinical Trial Description

Hematological malignancies including T-cell acute lymphoblastic leukemia (T-ALL), T cell lymphoma (TCL), natural killer cell lymphoma (NKL) and acute myeloid leukemia (AML) are aggressive diseases which may express the early T cell development molecule CD7.

T-ALL represents 15% of childhood and 25% of adult ALL, and T-ALL patients are prone to early disease relapse and suffer from poor outcomes. Several immunophenotypic classifications have been proposed. According to European Group for the Immunological Characterization of Leukemias (EGIL), the presence of cytoplasmic or membrane expression of CD3 defines T-ALL. Four subgroups are proposed: (TI) the immature subgroup or pro-T-ALL is defined by the expression of CD7 and cCD3; (TII) pre-T-ALL also expresses CD2 and/or CD5 and/or CD8; (TIII) or cortical T-ALL shows CD1a positivity; (TIV) finally, mature T-ALL is characterized by the presence of surface CD3 and CD1a negativity.

Over the past few years, T cells modified with lentiviral chimeric antigen receptor (CAR) gene have been studied in different clinical settings. CD7 is a T cell surface protein that plays important role in T cell-B cell interaction in early lymphoid development, displays membrane expression early during T cell development before TCR rearrangement, and persists through terminal stages of T cell development, and a well-known marker for T-ALL. CD7 is considered a promising target for the treatment of T-ALL, TCL, AML and NKL. In this study, we will investigate CD7 CAR-T in combination with alternative targeting CAR-T cells as a new strategy to treat hematological malignancies.

The T cells from patients or transplantation donors will be genetically modified with lentiviral CAR vector to recognize CD7 expressed on the surface of the cancer cells. The engineered T cells will be applied to patients through intravenous delivery.

The purpose of this clinical trial is to assess the feasibility, safety and efficacy of multiple CAR-T cell therapy in hematological malignancies. Another goal of the study is to learn more about the function of CAR T cells and their persistence in the patients. ;

Related Conditions & MeSH terms

• Acute Myeloid Leukemia
• Leukemia
• Lymphoma
• NK Cell Lymphoma
• Precursor Cell Lymphoblastic Leukemia-Lymphoma
• Precursor T-Cell Lymphoblastic Leukemia-Lymphoma
• T-cell Acute Lymphoblastic Leukemia
• T-cell Acute Lymphoblastic Lymphoma

• NCT number: NCT04033302
• Study type: Interventional
• Source: Shenzhen Geno-Immune Medical Institute
• Contact: Lung-Ji Chang, Ph.D
• Phone: 86-0755-86725195
• Email: c@szgimi.org
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: September 1, 2019
• Completion date: December 31, 2023