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

NCT ID: NCT03030976

Last Updated: 2017-02-07

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE1
• Total Enrollment: 5 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-03-31
• Study Completion Date: 2018-03-31

Brief Summary

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.

Detailed 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.

Conditions

Systemic Lupus Erythematosus (SLE)

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Reduce B cells

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.

Group Type: EXPERIMENTAL

cyclophosphamide

Intervention Type: DRUG

Patients receive cyclophosphamide (Cy) on day -2 and day -1 to reduce B cells. The dose is 0.5g/m2/d.

Treatment of SLE

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.

Group Type: EXPERIMENTAL

anti-CD19-CAR-T cells

Intervention Type: DRUG

A 2nd CAR, CD19 as target protein, 4-1BB as co-stimulator, and optimized the spatial conformation by a suitable hinge \& transmembrane domain sequences. Patients infused with anti-CD19-CAR-T cells transduced with lentivirus on day 0 in the absence of disease progression or unacceptable toxicity to treatment of SLE. The dose is 1E6\~1E7 CD19-CAR positive T cells. The cells infusion process may last for 30 min.

Interventions

cyclophosphamide

Patients receive cyclophosphamide (Cy) on day -2 and day -1 to reduce B cells. The dose is 0.5g/m2/d.

Intervention Type: DRUG

anti-CD19-CAR-T cells

A 2nd CAR, CD19 as target protein, 4-1BB as co-stimulator, and optimized the spatial conformation by a suitable hinge \& transmembrane domain sequences. Patients infused with anti-CD19-CAR-T cells transduced with lentivirus on day 0 in the absence of disease progression or unacceptable toxicity to treatment of SLE. The dose is 1E6\~1E7 CD19-CAR positive T cells. The cells infusion process may last for 30 min.

Intervention Type: DRUG

Other Intervention Names

Cy; 2nd CAR-T

Eligibility Criteria

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)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 69 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

RenJi Hospital

OTHER

Sponsor Role: collaborator

Shanghai GeneChem Co., Ltd.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Qiang Guo, Doctor

Role: PRINCIPAL_INVESTIGATOR

RenJi Hospital

Locations

Shanghai Jiaotong University School of Medicine, Renji Hospital

Shanghai, , China

Site Status: RECRUITING

Countries

China

Central Contacts

Qiang Guo, Doctor

Role: CONTACT

bluedescent@126.com

86-21-63835620

Xuejun Yu, Master

Role: CONTACT

yuxuejun@genechem.com.cn

86-21-51320189 ext. 8306

Facility Contacts

Qiang Guo, Doctor

Role: primary

bluedescent@126.com

86-21-63835620

Other Identifiers

CD19-CART for SLE

Identifier Type: -

Identifier Source: org_study_id