A Study of CD19 Redirected Autologous T Cells for CD19 Positive Systemic Lupus Erythematosus (SLE)

Shanghai GeneChem

Status and phase: Unknown; Phase 1

Conditions: Systemic Lupus Erythematosus (SLE)

Treatments: Drug: cyclophosphamide; Drug: anti-CD19-CAR-T cells

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT03030976

CD19-CART for SLE

Details and patient eligibility

About

CAR-T therapy was therefore proposed and has been recently used for cancer treatment. It has been hailed for its promising remission rates after early stage clinical trials for acute lymphoblastic leukemia. However, CAR-T therapy is seldom used for autoimmune diseases. Researchers only use it for the treatment of multiple sclerosis (MS, an autoimmune disease of the central nervous system). SLE is a kind of autoimmune diseases which involving multiple systems, organs and with the present of a variety of autoantibodies. In the conventional treatment options, SLE could be treated with chemotherapy drugs or hormone drugs. But chemotherapy and hormone drugs could barely cured SLE. And now, chimeric antigen receptor modified T cell infusion maybe an effective treatment to solve these problems. The investigators use a 2nd CAR- T with the optimized hinge and transmembrane domain to treat patients with SLE. The purpose of this study is to assess the safety and efficacy of this 2nd CAR-T cells in the treatment of SLE.

Full description

This study is being conducted to assess anti-CD19-CAR-T cells safety and efficacy in treating patients with systemic lupus erythematosus（SLE）.The investigators constructed a 2nd CAR, using CD19 as target, using 4-1BB as co-stimulator, and optimized the spatial conformation by a suitable hinge and transmembrane domain sequences. The infusion dose is (1-10)E6 CAR positive T cells/kg, and the specific cells numbers depends on the situation of individual CAR-T cells preparation.

Enrollment: 5 estimated patients

Sex: All

Ages: 18 to 69 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Clinical diagnosis of systemic lupus erythematosus (SLE) patients
• Patients with CD19+ B-cell SLE as confirmed by Flow Cytometry
• Age: 18-69 years old
• Creatinine < 1.5 mg/dl
• cardiac ejection fraction>55%
• hemoglobin>9g/dL
• Bilirubin <2.0 mg/dl
• Successful test expansion of T-cells
• Adequate venous access for apheresis, and no other contraindications for leukapheresis
• Voluntary informed consent is given

Exclusion criteria

• Pregnant or lactating women
• Uncontrolled active infection
• Concurrent use of systemic steroids. Recent or current use of inhaled steroids is not exclusionary
• Previously treatment with any gene therapy products
• Feasibility assessment during screening demonstrates<5% transduction of target lymphocytes, or insufficient expansion (<5-fold) in response to CD3/CD28 costimulation
• Any serious, uncontrolled diseases (including, but not limit to, unstable angina pectoris, congestive heart failure, serious arrhythmia)

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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5 participants in 2 patient groups

Reduce B cells

Experimental group

Description:

Patients receive cyclophosphamide to reduce B cells before CD19-CART infusion. It will also reduce the side effects of cell damage due to antitumor activity.

Treatment:

Drug: cyclophosphamide

Treatment of SLE

Experimental group

Description:

Patients receive anti-CD19-CAR-T cells to treatment of SLE. The purpose of this study is to assess the safety and efficacy of CD19 CAR-T cells in the treatment of SLE.

Treatment:

Drug: anti-CD19-CAR-T cells