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

Systemic Lupus Erythematosus (SLE) Clinical Trial

Official title:

An Open-labeled, Uncontrolled, Single-arm Pilot Study to Evaluate Cellular Immunotherapy Using CD19-targeted Chimeric Antigen Receptor Engineered T Cells in Patients With CD19+ B Cell Systemic Lupus Erythematosus (SLE)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03030976
• Other study ID #: CD19-CART for SLE
• Status: Recruiting
• Phase: Phase 1
• First received: January 22, 2017
• Last updated: February 4, 2017
• Start date: March 2017
• Est. completion date: March 2018

Study information

• Verified date: January 2017
• Source: Shanghai GeneChem Co., Ltd.
• Contact: Qiang Guo, Doctor
• Phone: 86-21-63835620
• Email: bluedescent[@]126.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 5
• Est. completion date: March 2018
• Est. primary completion date: January 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 69 Years

Eligibility

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)

Related Conditions & MeSH terms

• Lupus Erythematosus, Systemic
• Systemic Lupus Erythematosus (SLE)

Intervention

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

Locations

Country	Name	City	State
China	Shanghai Jiaotong University School of Medicine, Renji Hospital	Shanghai

Sponsors (2)

Lead Sponsor	Collaborator
Shanghai GeneChem Co., Ltd.	RenJi Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety of CAR-T cell(i.v.)by number of patients with adverse event	adverse event is evaluated with CTCAE, version 4.0	6 weeks
Secondary	Number of patients with tumor response	summarize tumor response by overall response rates	8 weeks
Secondary	3. Detection of transferred T cells in the circulation using quantitative -PCR		6 weeks